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Thursday, March 04 2010
Count Rosa DeLauro among those who remain highly critical of the Food & Drug Administration’s handling of GlaxoSmithKline’s type 2 diabetes drug rosiglitazone. The Connecticut Democrat, whose chairmanship of the Agriculture Appropriations Subcommittee gives her something like life-and-death authority over FDA, made her feelings on the subject abundantly clear during an Institute of Medicine workshop on regulatory science February 26.
It is no surprise that DeLauro has concerns about Avandia, nor is it news that she would comment on the renewed controversy around the drug triggered by a Senate Finance Committee report released a week ago. (See “Avandia Revisited,” The RPM Report, February 2010.)
What is perhaps surprising is DeLauro’s view that the Avandia issue is central to a discussion of regulatory science, and that she would bring it up in the context of the agency’s desire to secure a sustainable funding stream for activities designed to keep it ahead of (or at least close to) the regulatory demands raised by cutting edge medicine.
Her remarks are worth reading, both to deepen the understanding of how the latest re-review of Avandia is likely to play out, as well as to underscore the limits that the change in leadership at FDA alone will have on shielding products from political controversy.
Praise For Hamburg
During the IoM event, DeLauro was warmly introduced by FDA Commissioner Margaret Hamburg, and then returned the favor by praising her “for the strong leadership she has shown in turning the agency around.”
Then DeLauro talked about how critical regulatory science is to FDA; indeed, DeLauro said, the idea that the agency would need support there is almost an oxymoron. “Regulatory science for drug development should already be built into the FDA, and should already be the essence of the agency,” she said. She recapped the history of FDA from 1906, underscoring how the agency was built as a leader in regulatory science and needs to be so again.
She received a warm ovation when she noted that she has overseen a 59% increase in the funding of the agency since taking over as subcommittee chair in 2007. Everything seemed set up for a pledge to continue the work to support the agency in re-establishing its leadership role.
Instead, she went after Avandia.
For the RECORD
DeLauro focused her remarks in particular on GSK’s RECORD study, which the company suggests vindicates Avandia’s safety profile. The Finance Committee flagged a number of concerns with that trial, and—as DeLauro noted—other publications have raised questions.
Still, her extensive critique is worth quoting at length, if only to illustrate the extent to which one powerful member of Congress has absorbed the latest elements of the case against Avandia. Those themes are sure to be aired when FDA revisits the application during an advisory committee meeting in July.
Here are her remarks on that theme, as transcribed by The RPM Report.
“As far as I know, the only study suggesting that Avandia was safe was a study known as the RECORD trial…The RECORD trial was sponsored by GlaxoSmithKline.
“Now I’m not a scientist but even to a layman’s eyes the RECORD trial posed certain problems.
“For one, both the physicians and the patients knew who were taking drugs. This does not make for scientifically sound clinical trials, and it creates a situation where there is the potential to manipulate clinical data.
“Further, it appears that Glaxo had inappropriate access to the data while it was being collected, which is a violation of the study’s scientific integrity and should alone invalidate it as an independent source of reassurance.
“And if it sounds like I am assigning bad intent to Glaxo here, consider a perspective by the Journal of the American Medical Association, which concluded that over half of the adverse events that were expected in this trial had somehow gone missing. Or consider that by the end of this trial, 40% of the patients assigned to take Avandia were no longer on the drug. How is it possible to assess the safety of a drug that the tests prove is not even taken?
“Finally, consider that every other analysis that we have seen, including one by the Harvard University Medical System and another analysis by Glaxo themselves found that Avandia tends to result in a 30%-40% increase in heart attacks.
“I harbor no ill will towards pharmaceutical companies. By bringing life saving drugs to the market place they are applying our countries greatest resource, the innovative spirit, to help people live longer, more productive lives. Most people at some point in their lives experience the direct reach and the power of these drugs to cure illness, heal wounds and halt disease. It has become part of the human experience, and I am joining you here today as someone who has felt that power deep down in her soul….
“None the less, it is completely reprehensible to me that many sufferers of diabetes might have suffered heart attacks or heart failure as a result of taking Avandia, especially when the dangers were known beforehand and a safer alternative exists.
“Sadly, these situations are too frequent these days….With every new case, they look less like outliers and more like a dangerous and systemic failure in our regulatory apparatus.
“Simply put, it has become abundantly clear that the safety and efficacy of prescription drugs must be based on independent, science-based evidence, and not on a company’s interpretation…To solve the problem we clearly need more independent regulatory science at the FDA, that needs to bridge that gap between basic research and new medical products.”
Different Views of Regulatory Science
DeLauro’s discussion of RECORD is noteworthy not just for the threat it poses to GSK, but also as an illustration that the definition of “regulatory science” is very much in the eye of the beholder. Industry would like to see an investment in regulatory science that helps reduce the cost and improve the success rate in clinical development—or, as DeLauro put it—tools “to bridge that gap between basic research and new medical products.”
DeLauro, though, also sees “regulatory science” as giving FDA the “tools to investigate thoroughly and efficiently the products that come under its review”—and a culture that stresses independence from industry influence.
As she put it at the IoM meeting, “the safety and efficacy of prescription drug medication must be based on independent, science-based evidence, and not a drug company’s interpretation of what constitutes this evidence. To solve this problem, we clearly need more independent regulatory science at the FDA.”
But even if RECORD is dismissed altogether, that doesn’t in fact do anything to change the argument about Avandia. The bottom line remains that some scientists (including some in FDA’s pharmacovigilance group) read the data as showing an unsupportable risk with the drug. Others (including some in FDA’s new drug review groups) see the risk as equivocal, and certainly outweighed by the benefit for at least some patients.
That is nothing new. In fact, DeLauro’s concerns—indeed, the new report released by the Finance Committee—do not represent new information about the safety profile of Avandia. Instead, they reargue the facts as they stood in 2007, when two sides looking at the same dataset reached divergent conclusions about whether continued marketing of the drug is appropriate. That debate played out publicly in the context of an FDA advisory committee and then again during an internal FDA Drug Safety Oversight Board meeting. (See “Avandia and the Commerical Impact of FDA’s Credibility Gap,” The RPM Report, September 2007.)
That round of debate ended when FDA decided to leave Avandia on the market with a new boxed warning. (See “Avandia’s Black Box,” The RPM Report, December 2007.)
What the new flare up makes clear is that, while the safety review may have ended with an agency action, the dispute over the science was anything but resolved.
Scientific Disputes
Improvements in regulatory science may help FDA do a lot of things, but they can’t help FDA settle disputes about the science itself.
In DeLauro’s view, the next step in the case of Avandia is clear: “I strongly urge the FDA to remove Avandia from the market until a truly independent, science-based advisory panel can evaluate the safety and effectiveness of the drug,” she said in a press release issued following the Finance Committee report. (Interestingly, she did not explicitly call for Avandia’s withdrawal in the IoM meeting.)
Of course, the notion that the key legislator overseeing FDA’s appropriation process has made up her mind about the appropriate handling of Avandia could itself be viewed as a threat to FDA’s ability to serve as an independent arbiter of regulatory science, a point gently made in a question posed to Hamburg after DeLauro’s remarks.
Neither the questioner nor Hamburg’s response made explicit reference to Avandia. Rather, the questioner noted that FDA is always under attack as either “too cautious or too lenient,” and wondered how the agency can maintain its “autonomy” when under such pressure.
Hamburg’s response strikes a delicate balance of acknowledging DeLauro’s concerns, while quietly but firmly asserting the importance of FDA’s role as the final arbiter of what is best for the public health.
“While I think we need autonomy in important aspects of our decision making, we also have a huge responsibility to a group of stakeholders, importantly including the American people.
“I would never want to convey that I think we should operate completely in isolation. I think, in fact, first and foremost, we have to answer to the American people. We also are part of a department, and part of an Administration.
“We have to use as our compass public health. We have to respond to our mission, which I think is consistent in terms of Administration, in good times or hard times, or in terms of funding
“It really comes down to what Congresswoman DeLauro was stressing, which is the importance of science and the importance of really bringing data and evidence to bear on our decision making.
“But it is certainly difficult, and it is difficult because the questions we have to answer are so tough, because…it depends on your perspective. ‘Too cautious,’ or ‘too lenient’?
“I would like to believe—but it simply isn’t true—that if you are a science driven agency that means all the decisions neatly unfold before you, and you use the data and you go forward. But we also have to recognize that another huge challenge for us is how do you resolve scientific disputes?
“There are many, many important questions where the data is not obvious or self-evident. Informed, hard-working and high-integrity scientists can disagree. So we also have to create an environment where there is a robust process for scientific decision making that allows all voices to be heard and makes sure that all available evidence is brought to bear.
“But at the end of the day, resolving those scientific disputes within FDA, using the best possible expertise from the outside, is one the primary and most difficult challenges that we face.”
Hamburg’s response stresses many of the themes of the 2010 drug review process, in particular the notion that “all voices be heard” while considering regulatory actions.
But, her quiet, understated follow-up is critical: “at the end of the day, resolving those scientific disputes within FDA” is part of the agency’s public health mission.
So far, at least, that has not happened with Avandia, as the latest flare up over the drug’s cardiovascular safety profile makes clear. Hamburg is clearly focusing on making that happen now, as the agency heads towards another review of the issue at the advisory committee this summer.
The danger for GSK is that FDA will decide that the only way to resolve the debate is to withdraw the product’s approval—but, so far, at least, Hamburg hasn’t bowed to that line of thinking.
If the agency is indeed able to bring the Avandia debate to a conclusion in a manner that satisfies “the American public”—or at least Rosa DeLauro—that would mark a significant accomplishment.
As Hamburg herself noted in concluding her thoughts on resolving scientific disputes at IoM: “It’s not an easy job.”
Comments? Email the author at windhover-dc@windhover.com
Wednesday, March 03 2010
Two weeks after FDA Commissioner Margaret Hamburg invited the Generic Pharmaceutical Association to come back to the table to negotiation a generic drug user fee program, the agency is shuffling the leadership of the Office of Generic Drugs in apparent anticipation of pushing towards an agreement.
Director Gary Buehler, who has led the office since 2000, is moving up become acting deputy director for operations in the Office of Pharmaceutical Science, the next level up in the Center for Drug Evaluation & Research.
In that role, “he will play a key role in the Center’s negotiations/activities on generic drug user fees, and in leading other critical programs in OPS, and spearheading our efforts to implement quality management systems for OPS business operations,” said Helen Winkle, director of the Office of Pharmaceutical Sciences.
“His longstanding experience and deep knowledge of FDA and of the generics industry has served the agency well and will be instrumental in helping us to advance our 2010 programmatic agenda,” she added.
OPS Assistant Director Keith Webber will be taking over as acting head of OGD while FDA conducts a search for a permanent director.
The change comes at a time when the backlog in generic drug approvals is approaching 2,000 applications, and the average review time for generic drug applications is now more than two years. Commissioner Hamburg acknowledged those challenges in a mid-February address to the GPhA annual meeting in Naples, Fla. And, Hamburg made clear, the agency hopes to revive the idea of solving the problem by negotiating a user fee program for generic drugs.
“We very much want to work with you to see generic drug user fees enacted this year,” Hamburg told GPhA. “Adequate and reasonable fees will be key to both more rapid review and to better surveillance.”
GPhA, for its part, supports a user fee program—provided the fee level is reasonable and tied to deliverables on the agency side that include performance metrics on review times and meetings with industry analogous to those in the Prescription Drug User Fee Act model.
Hamburg acknowledged the need for the agency to contribute on that front: “We have an essential part to play, too, in providing your industry with meaningful benchmarks and in performing to those goals.”
“I do hope we can return to the negotiating table soon,” she added.
The management reshuffling should help to advance that goal. First, Buehler’s extensive experience in OGD should make him the ideal person to help FDA flesh out its user fee proposal. But second, the change in leadership at OGD also sends a clear signal to industry about the agency’s desire to change the status quo.
Of course, any transition in leadership can be a double-edged sword.
The change in leadership at OGD may help the agency show industry it is serious about bringing “new energy” to working through the backlog, Alston & Bird attorney Marc Scheineson pointed out. However, he noted, past history would suggest that a transition atop OGD will slow down reviews in the short term, since the tendency is to “slam on the brakes” while new leadership gets up to speed.
Even that outcome, however, could serve as an encouragement to move forward on user fees, since a further step-up in the backlog and review times would only increase industry’s desire to set firm deadlines on reviews.
Webber’s background will make him an interesting caretaker for OGD at a time when the agency may be developing policy to implement a follow-on biologics regulatory pathway. Webber first joined FDA in the Center for Biologics Evaluation & Research, and has expertise in protein analysis.
FDA is expected to recruit for the permanent head from outside, though FDA candidates are expected to be considered.
Comments? Email the author at windhover-dc@windhover.com
Monday, March 01 2010
The headlines were predictable immediately after the White House Healthcare Reform Summit:
“No Clear Winner in Seven-Hour Gabfest” – Politico
“More Talk, No Deal at Health Summit” – Wall Street Journal
“Obama’s Health Summit Talkathon” – Washington Post
“Bottom Line On Health Care Summit: Dems Push Ahead” – AP
Some news organizations had already issued a comprehensive list of “winners and losers” less than 10 minutes after the summit had concluded. But the real take home message from the White House Summit was there were no “losers.”
Make no mistake, putting on the event itself was a calculation intended to produce political theater that benefited the President and help the administration get some traction for the White House’s top domestic policy agenda item. And Obama did benefit from the public meeting. But so did some Republicans. And so did other Democrats. And so did the viewers who took time to tune in for a few minutes or the full day.
In short, the White House Summit, warts and all, produced the kind of discussion on a national issue of great controversy that many hoped would take place. There were talking points, sure. And there were carefully orchestrated maneuvers, such as House Minority Whip Eric Cantor (R-Va.) repeatedly pointing to the 2,000 page-plus bill, or House Rules Committee Chair Louise Slaughter (D-NY) retelling a story of how a woman had to use her dead sister’s dentures because she couldn’t afford her own. But those were side points to the substantive discussions that occurred in the majority.
Policy Wonk Obama. It’s difficult to find any single person more polarizing to an American public than a current sitting American President. A 50% approval rating is typically good news. Like him or lump him, though, Obama demonstrated a firm grasp of both the large issues, such as the individual mandate to buy health insurance, and the detailed nuances of how the Congressional Budget Office scores premium increases over time. It was at the very least reassuring to see the President know the issues from top to bottom. Put simply, Obama was very good. Moreover, Obama presided over the full meeting, which went roughly six and a half hours.
In the end, he gave a defense of the comprehensive he has favored over an incremental approach:
“An interesting thing happened a couple of weeks ago, and that is a report came out that for the first time, it turns out that more Americans are now getting their health care coverage from government than those who are getting it from the private sector. And you know what? That's without a bill from the Democrats or from President Obama. It has nothing to do with, quote-unquote, ‘Obamacare.’
It has to do with the fact that employers are shedding employees from health care plans. And more and more folks, if they can, are trying to get into the Social Security system and the Medicare system earlier through disability or what have you, so that they can get some help.... The reason we didn't do it is because it turns out that baby steps don't get you to the place where people need to go. They need help right now.”
Lamar Alexander: The Right Responder. Republicans could not have picked a better first responder to the President than Lamar Alexander, the Tennessee Republican who is the Senate Republican Conference Committee Chairman. He came off as reasonable, knowledgeable, confident, and respectful. Here’s a snippet from Alexander’s response:
“When I went home for Christmas after we had that 25 days of consecutive debate and voted on Christmas Eve on health care, a friend of mine from Tullahoma, Tennessee, said, ‘I hope you'll kill that health care bill.’ And then, before the words were out of his mouth, he said, ‘But we've got to do something about health care costs. My wife has breast cancer. She got it 11 years ago. Our insurance is $2,000 a month. We couldn't afford it if our employer weren't helping us do that. So we've got to do something.’”
The message, skepticism aside: Republicans aren’t here to say no, we want you to go in a different, incremental direction.
Alexander listed six ideas Republicans would be willing to work with Democrats on:
1) A small-business health care plan.
2) Helping Americans buy insurance across state lines.
3) Put an end to junk lawsuits against doctors
4) Give states incentives to lower costs.
5) Expanding health savings accounts.
6) Eliminate preexisting conditions.
Tom Coburn Speaks, Obama Listens. There are few, if any, members of the Senate more conservative than the Oklahoma doctor Tom Coburn. It was surprising, then, to see on live television Obama listening closely to what Coburn had to say on health care waste, fraud, and abuse, and watch him take copious notes while Coburn spoke. In fact, at the very end of the day, Obama went back to his notes to point out the many points on which him and Coburn agree.
Coburn during his opening remarks:
“You know, when you compare the private sector fraud rates, it's 1 percent compared to Medicare and Medicaid. You know, there's estimates that there's $15 billion worth of fraud in Medicaid a year in New York City alone. So we haven't attacked that. We haven't gone where the money is. And my hope would be that we would look at where the money is. And if truly it's accurate -- and I don't know many people that will disagree that $1 in $3 doesn't help somebody get well and doesn't prevent it, then we ought to be going for that $1 in $3.”
Obama wrapping up the meeting:
“With respect to bending the cost curve, we actually have a lot of agreement here. This is an area where if I sat down with Tom Coburn, I suspect we could agree on 95 percent of the things that have to be done, because the things you talked about in terms of -- and I wrote some of them down. In terms of reducing medical errors, in terms of incentivizing doctors to coordinate better and work in groups better, in terms of price transparency, improving prevention, those are all things that not only do I embrace, but we've included every single one of those ideas in these bills.”
The Clinton Boogie Man Makes His Point. No one is perhaps as reviled in Democratic circles in the health care reform debate as Tennessee moderate Democrat Jim Cooper. The prominent House Blue Dog member is often blamed in part for the failure of Bill Clinton’s failed 1993-1994 effort because of his opposition. Liberals dislike him, to put it lightly. That’s why what he says publicly is being carefully watched by both sides of the aisle in 2010.
Obama went to Cooper in the afternoon, and the Tennessean gave one of the most thoughtful, persuasive remarks of the day:
“Mr. President, I'm thankful you have appointed a presidential fiscal responsibility commission, with Alan Simpson and Erskine Bowles, to try to force us as a Congress and force the nation to address these fundamental problems, because if you love Medicare, you need to act to save it fast. Every day matters.
A report will come out issued by the Treasury Department. It comes out every year. It'll come out in the next few days. It's the only report that uses real accounting to describe America's fiscal problems, and the news is not pretty. It will reaffirm what's been discussed here about Medicare and Medicaid and other vital American programs being deeply in the hole. And the opportunity of costs for delay is extraordinary.
So we can face these problems, Mr. President. We can solve them with political will, but the talking points won't do it. We've got to acknowledge the real questions.
And as every business person in America knows, if you can't measure it, you can't manage it. And too many people in the federal government are refusing to measure it, much less take the tough votes that are required, because the reason we have a Medicare Advantage program, Mr. President, as you know, is in 2003, when the other party was completely in charge of everything here, we passed a program that before now was almost completely unfunded and added $8 trillion in one bill to our children and grandchildren.
Now, those benefits if offered should be paid for. So this is a challenge for everybody in both parties, because nobody's hands are clean in this, but let's have a new day, a new beginning. I think we could do this. And this bill is a great place to start, because if you don't think this bill reduces the deficit enough, according to CBO, vote for more savings. If you want to reform Medicare some more, vote for it. Don't just talk a good game.
So I hope the American people are watching, because -- and they're going to be watching after the cameras are turned off, too. And I'm thankful you called this meeting, because this is a moment of truth for our country. And together, we can solve this problem.”
In the end, it’s about philosophy. Maybe no one summed up the critical question at hand better than Texas Republican and ranking Energy & Commerce Committee member Joe Barton:
“Mr. President. I want to commend you for asking us to come here. And I will saying that never have so many members of the House and Senate behaved so well for so long before so many television cameras. So if we ever get to a conference committee, we may want you to be the moderator.
I do think, though, that there is a fundamental difference in the vision that you and your friends on the majority have put forward and the vision that myself and those of us in the minority have put forward: It's the pivotal role of the government.
We believe that we should use free markets to empower people and give them choices. And for the best of intentions, yourself and most of your allies in the Democratic Party seem to believe that the government, either through a mandate or through a regulatory requirement, knows better and will do better for health care for most Americans.”
Barton encapsulated in his brief remarks the central disagreement at the heart of the health care reform debate and it was clear to everyone watching: If you want more government involvement in health care, you’re for them. If you don’t, you’re for us. For those watching on television, the question was simple: which is it?
Comments? Email the author at windhover-dc@windhover.com
Monday, March 01 2010
Bristol-Myers Squibb cleared an important milestone, winning an approval recommendation after an advisory committee review of the transplant drug belatacept.
The committee review was tough, but one item in the preview materials posted by the Food & Drug Administration caught our eye as a sign of tougher times for advisory committees in general: FDA issued a formal conflict-of-interest waiver for Richard Mann, who heads the kidney and pancreas transplantation program at Robert Wood Johnson Medical School.
Under new rules set by the FDA Amendments Act, the agency is directed to review potential conflicts-of-interest of advisory committee members carefully, and issue waivers sparingly. (You can read more about this issue in The RPM Report, here.)
In this case, the agency wanted Mann to serve as a temporary voting member, but spotted a potential conflict: he was listed as a co-investigator on a trial involving "competing products to belatacept." The study drugs are not identified in the waiver document, but it does explain the circumstances.
Mann was listed as a co-investigator "as a matter of policy" by the medical school; he is not an active participant in the trial. In fact, he "has filed the appropriate paperwork" to have his name removed from the study. Moreover, the size of the potential conflict is "$0-$50,000 per year."
However, FDA notes, the fact remains that his employer has an interest in competing products, and therefore Mann has an "imputed conflict of interest."
The agency considered 10 other transplant nephrologists for the committee. Four couldn't attend, one did not submit the paperwork for review, and the other five were "recused due to conflicts of interest"--presumably more serious ones than Mann's.
In other words, Mann was the only transplant nephrologist available for the meeting who didn't have a direct conflict of interest. Waiver granted.
But that also means one less waiver for the agency to use later in the year. Under FDAAA, supplies of waivers are limited--essentially to a small percentage of committee members overall--so issuing this one means one fewer to use later on. And, as the standard applied to Mann shows, it will be hard to seat committees without using at least some of those precious waivers--especially for specialty products.
Comments? Email the author at windhover-dc@windhover.com
Monday, February 22 2010
There are few drugs approved by FDA that open old regulatory wounds like GlaxoSmithKline’s Avandia.
The Type II diabetes therapy has been the subject of intense scrutiny by Congress and FDA ever since Cleveland Clinic cardiologist Steve Nissen published a meta-analysis in the New England Journal of Medicine on May 21, 2007 indicating that rosiglitazone was linked to a substantial increase (30%- 40%) in risk of cardiovascular adverse events compared to comparator groups.
The data were vetted by a joint FDA panel of the Drug Safety & Risk Management and Endocrinologic & Metabolic Drugs advisory committees during a July 30, 2007 meeting. The joint committee voted 20-3 that Avandia increases cardiac ischemic risk but subsequently voted 22-1 against withdrawal of the TZD.
The panel meeting surfaced an “internal disagreement” between the Office of New Drugs and Office of Surveillance & Epidemiology over whether to withdraw rosiglitazone over heart attack risks.
On October 2, 2007, FDA’s Drug Safety Oversight Board voted (8-7) to keep Avandia on the market. The non-public vote was questioned by ranking Senate Finance Committee Republican Charles Grassley (Iowa) due to the lack of transparency.
On November 14, 2007, FDA issued a black-box warning for Avandia warning of heart attacks. GSK agreed to conduct a long-term postmarket safety trial of Avandia compared to competitor Takeda’s Actos to confirm whether a higher CV risk for rosiglitazone exists; the trial was named TIDE. The TIDE trial is expected to be complete in 2015.
End of story, right? Not quite. Avandia is back.
The Senate Finance Committee released a 300-plus page report on February 22 bringing to light internal emails and memos related to Avandia and heightened CV risks that answer the questions: what did they know and when did they know it? The quick answers appear to be that GSK was aware of link to an increase in heart attacks and the association was known prior to the Nissen analysis. Moreover, the company was aware that as early as 2004, their postmarket study RECORD, which evaluated the potential for an increase in CV events, was underpowered from the start to do so.
To read the Finance Committee report, including internal memos and emails, click here.
In addition to the Finance Committee report, an analysis by OSE Associate Director for Science David Graham and OSE official Kate Gelperin claims that 500 heart attacks and 300 cases of heart failure occur every month due to Avandia. The report says that continuing with the TIDE trial would be “unethical” and calls for the drug to be withdrawn.
FDA will now hold another advisory committee to go over all of the available data on Avandia during a July FDA advisory committee.
FDA Commissioner Margaret Hamburg says she will wait for the guidance of the FDA panel before deciding how to move forward on Avandia. The agency did issue a health care provider letter on February 22:
FDA notified healthcare professional and patients that it is reviewing the primary data from a large, long-term clinical study, RECORD, on possible cardiovascular risks with the diabetes drug, Avandia (rosiglitazone). In addition to the clinical trial, a number of observational studies of the cardiovascular safety of rosiglitazone have been published and FDA has been reviewing these on an ongoing basis.
These reviews are ongoing and no new conclusions or recommendations about the use of rosiglitazone in the treatment of type 2 diabetes have been made at this time. Once FDA completes its review of the data from the RECORD study, the agency will present the totality of new and existing cardiovascular safety data on rosiglitazone at a public meeting in July 2010. The Agency will provide an updated assessment of the risks and benefits of rosiglitazone in the treatment of type 2 diabetes.
FDA recommends that healthcare professionals follow the recommendations in the drug label when prescribing rosiglitazone. This includes a Boxed Warning. Patients should continue taking rosiglitazone unless told by their healthcare professional to stop. Patients who are concerned about the possible risks associated with using rosiglitazone should talk to their healthcare professional.
Revisiting Avandia carries a number of broader implications for drug companies:
·Splitting the drug center in two. The FDA Amendments Act (FDAAA) of 2007 appeared to have settled this debate. The proposal of separating the Center for Drug Evaluation & Research into two separate review groups, one for efficacy and one for safety, was strongly considered as a solution to the general concern that FDA was not giving safety adequate prominence in its drug reviews. The proposal was eventually set aside in favor of risk evaluation and mitigation strategies (REMS), legal authorities, and funding. As the industry enters the next reauthorization cycle of the prescription drug user fee act, splitting CDER in two will likely surface again. Congressional hearings and a high profile advisory committee on Avandia could provide momentum to such a proposal, at least in the near term as stakeholders prepare their initial ask-fors in PDUFA V.
·More advisory committees. One thing becomes crystal clear after a thorough reading of the Senate Finance Committee report and the Graham analysis: there will be more transparency in 2010. Drug manufacturers should expect more advisory committees in the near-term, both product-specific and topical.
·A tilt toward OSE? Drug review and drug safety official currently operate under “equal voice” in the drug center where OSE and OND have equal say over the risk/benefit profile of a drug under review or already on the market. That balance could tilt slightly in favor of OSE officials in the near-term as FDA re-enforces the role of the drug safety group.
·FDA look-backs. One of the first questions we asked Commissioner Hamburg when she became head of FDA was whether she would re-review controversial decisions by the previous administrations on specific drugs. Her answer: “I hope that my leadership will be marked by a strong and clear emphasis on science-based decision-making, and that if there's a question about a drug on the market, I would be looking at it in terms of what is the available evidence—is it safe and is it effective—and if there are concerns about its safety I would have no hesitation about examining it more closely and taking action.” Hamburg will have her chance to do just that. Although Avandia is unlikely to be the first of many, it does set a precedent to be the first of a few.
While GSK will have to wait until July for clarity on a final verdict on Avandia, the early implications for the rest of the drug industry are already taking shape. The question is whether the fallout from revisiting Avandia will be short-lived or long-lasting.
Comments? Email the author at windhover-dc@windhover.com
Saturday, February 20 2010
Neither Amgen nor Johnson & Johnson could possibly have imagined three years ago that they would be registering oncologists in a program intended to curtail use of two blockbuster products, the erythropoiesis stimulating agents Aranesp (darbepoetin) and Procrit (epoetin).
But, after a long and difficult period of safety scrutiny, that is exactly what the companies are doing, thanks to a Risk Evaluation & Mitigation Strategy announced February 16.
The REMS requires oncologists to enroll in a safe use program called APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe Use of ESAs). Basically, physicians won’t be able to prescribe Amgen’s Aranesp or Johnson & Johnson’s Procrit for use with chemotherapy unless they’re enrolled in the program and agree to use the products—once given almost routinely with all types of chemotherapy—purely in the context of avoiding the need for transfusion in patients whose treatment regimen is not intended to be curative.
The REMS is based on safety risks, including data that ESAs can cause tumors to grow faster and/or result in earlier death in patients with cancer. (You can read more about the REMS in The Pink Sheet DAILY.)
Training oncologists to comply with sharply restricted labeling is obviously not something Amgen and J&J ever wanted to do. But, given all that has happened over the past three years with the brands, there are at least three silver linings for the companies in the program.
1.It’s done. The blockbuster has now been reborn as a niche product, but at least that’s something. FDA’s ability to mandate the REMS is better than the oncology indication being revoked completely. (See “Cut to the Bone: Amgen Faces Further Aranesp Declined Ahead of Denosumab,” The RPM Report, November, 2008). Plus, the REMS isn’t as strict as it could have been; for example, there’s no patient registry involved, and FDA didn’t restrict the indication further than it already has.
And there is undeniably an upside to bringing this chapter to a close, and by giving Amgen and J&J a message to bring to their oncologist customers. Prescribers will have a year to enroll in the program and complete the training if they want to keep prescribing ESAs. How will they enroll? “Contact your local Amgen or Centocor Ortho Biotech field representative,” says the “Dear Doctor” letter. (There is also an on-line registration.) EPO may not be a blockbuster in oncology anymore, but both companies have other products to sell in that market.
2.It’s done now. It may not feel that way to the sponsors, but Amgen and J&J are probably lucky they were able to go through the REMS process while the post-marketing safety authorities are still so new. FDA is facing increased pressure from providers and other stakeholders to open up the REMS process overall in the way have done with the opioid REMS. In that class, FDA’s actions have made health care stakeholders happy, but left the product manufacturers in the distinctly disconcerting position of being just one of many stakeholders—and probably not the most important—in a process that will radically change the regulation of their products. (See “The Opioid REMS: Health Care Reform, One Class at a Time,” The RPM Report, February 2010).
For the ESAs, Amgen and J&J were able to complete the process as the sort of bilateral negotiations typical to labeling changes. Amgen says that it, FDA and Centocor Ortho Biotech were the main parties involved, though “multiple parties were involved” and “various healthcare providers were consulted.” This means there was greater control for the companies than for the manufacturers currently involved with the opioid REMS.
We’re betting that won’t be the model too often in the future. Kaiser Permanente, for example, is asking FDA to make the opioid model more routine—and specifically cited the ESAs as an example of a class where stakeholder input should be broad and public. (See “Kaiser Pushes Back on REMS,” below.)
And the American Society of Clinical Oncology (ASCO) is not happy about being left out of this negotiation as well. In a communication sent to its members, ASCO expressed concern about the process and the outcome. (See below for the full text of ASCO’s letter.)
ASCO says it is gathering comments from its members and will follow up directly with FDA. While that could potentially lead to refinements to the ESA REMS, we bet it will more likely mean that FDA assures ASCO that it will be a party to future discussions of class-wide REMS that affect its members.
3.The REMS will complicate the path for competitors. Three years ago, ESAs were the opportunity fueling the follow-on biologics debate. That has obviously changed, both because the market for ESAs is shrinking—and the legislative path for FOBs isn’t doing much better in the context of the stalled health care reform debate.
Still, the REMS will most likely raise the bar on follow-ons in the class even higher. In theory, new manufacturers of ESAs with an oncology indication might have to establish their own programs, and that means both more work and the unenviable task of convincing oncologists to spend time enrolling in a second program. On the other hand, it’s possible that the REMS could be shared by the whole class at that point—but that would, in effect, have follow-on sponsors encouraging oncologists to register with Amgen.
“It’s difficult to say what will happen in the future,” said Patricia Keegan, director of the Division of Biologic Oncology Products, during a media call February 16, “but I can’t see a reason why a product that acted through a similar mechanism with similar actions would be treated differently.”
For now, the registry does not apply to the use of ESAs outside the oncology setting (including use of Aranesp and Procrit). That is likely to change: A REMS is still in process for the use of ESAs in renal disease, and FDA is currently preparing for an advisory committee review of the indication. (See “ESAs in Renal Use May Face New FDA, CMS Constraints; REMS Still In Progress,” The Pink Sheet, January 11, 2010.)
Roche’s Mircera has FDA approval for use in the renal failure setting, but due to Amgen’s patents, it can’t be marketed until mid-2014 (See “Patent Power: Roche Concedes Case over Amgen’s EPO,” The Pink Sheet, December 23, 2009). Takeda and Affymax are also developing a follow-on ESA called Hematide for the renal disease market. Takeda said it is too soon to discuss what the implications of the REMS will be for its product.
Like essentially every REMS in the early years of the new authority, this one was precedent setting.
“We’ve not yet faced a REMS that’s applied to multiple agents,” Keegan said. In addition, “we’ve not yet faced a REMS where these elements to ensure safe use would apply to only one of the approved indications.”
She added that restricted pharmacy distribution, common in past REMS, wasn’t a practical model for ESAs since the drugs are primarily distributed through physician offices and hospital-based settings. This is also the first time a gradual implementation has been used with a registration; in this case, oncologists can begin registration March 24, but they have a year to fully comply.
Comments? Email the author at windhover-dc@windhover.com
Saturday, February 20 2010
On February 16, 2010 ASCO sent an alert to members, informing you of a new Risk Evaluation and Mitigation Strategy (REMS) for ESAs. Since then, ASCO has received numerous communications from members expressing concern about the burdens this program will impose on patients and physicians.
Oncologists are trained to treat patients with potent drugs and to manage potentially severe side effects of cancer treatment. We agree that it is critical for oncologists and other physicians to understand the risks and benefits of the drugs they prescribe, and to share this information with patients in a manner that is meaningful in the context of their individual treatment plans.
A REMS program should build upon existing processes of informed consent, continuing education, and the use of practice guidelines, and should not be duplicative of them. Oncologists continually struggle to provide high quality cancer care in the face of dwindling resources and growing administrative burdens. While ASCO supports efforts to raise risk awareness and promote patient safety, we strenuously object to duplicative requirements that further diminish time and resources available for patient care.
ASCO has noted with growing concern the process by which REMS are imposed without input from the physician community.
ASCO and its members were not part of the development of this latest REMS, and yet the resulting system will have a significant impact on the day-to-day practice of hematology and oncology.
There is a precedent for the FDA seeking stakeholder input as they consider a REMS program. When the FDA was initially considering a class wide REMS for opioid drugs, the agency held open meetings and solicited public comment on the proposed program. ASCO attended these meetings, submitted comments, and presented public testimony. In our comments we expressed physicians’ concerns, proposed practical solutions, and pledged to work with FDA on a program that would protect patient safety without impeding access to quality medical care.
When oncologists will be asked to employ a REMS in the clinic, ASCO feels strongly that our members should be represented during the development or review process.
While we vigorously advance our comments and concerns to the FDA, please note that enrollment for this program will begin on March 24th, 2010, and providers who do not enroll will no longer be able to prescribe ESAs.
We appreciate all of the comments we have received to date and will keep you informed of any new developments.
Comments? Email the author at windhover-dc@windhover.com
Monday, February 22 2010
By Ed Silverman
File this one under Regulatory Setback Syndrome. The FDA decision to issue a complete response letter to XenoPort and GlaxoSmithKline for their Horizant drug to treat Restless Leg Syndrome appears to have stunned the drugmakers. In a conference call this morning with analysts, XenoPort chief executive Ron Barrett confessed he didn't see it coming until the FDA missive arrived yesterday.
"It certainly did surprise us," he told the listeners, insisting the issue was never raised in any discussions with the agency during the entire pre-approval processs. "Many of the activities that you would expect to happen going into a PDUFA date had and were happening, including the REMS, and this one came out of left field."
What went wrong? The FDA bounced the drug because a trial showed a cancer risk in rats, specifically a prevalence of pancreatic acinar cell tumors in male rats. Interestingly, a similar finding showed up in Pfizer's Neurontin (gabapentin), which is approved to treat refractory epilepsy, and Barrett said the strength of the signal was no worse than what was seen with the Pfizer drug.
The FDA acknowledged that findings in lab animals don't necessarily translate into risk in humans, Barrett continued, adding that the agency "noted that gabapentin products have been available for over 15 years, and they do not appear to be associated with a clinical signal for pancreatic cancer based on analysis of spontaneous reports in the adverse event reporting system."
The issue for the FDA, though, is that treating epilepsy is a more serious matter than Restless Leg Syndrome, a line of thinking that may bolster those who have criticized the marketing surrounding the condition, even though it is deemed to be kosher by the National Institute of Neurological Disorders and Stroke (take a look).
For now, the implications for XenoPort are more immediate and severe than any marketing debate. Glaxo already announced plans to exit research into pain, and Barrett concedes their deal for the drug may be up in the air, possibly threatening further development of Horizant to treat neurothropic pain, where a Phase II trial failed last year, and migraines. Barrett, however, refused to offer any definitive insights on this particular topic. "The question of risk-benefit is something that is going to have to be probed for each indication."
In response to a question about Glaxo's ability to end the deal based on development setbacks, Bennett offered this sobering reply: "I think it's fair to say that any license agreement of this type is going to have termination provisions. And without speaking to language that might be redacted, I think it is reasonable to expect that this agreement is no different than that GSK would have the ability to terminate for reasons that include what you have articulated, among others. So I think people should understand that a termination by GSK is possible in the wake of this news, as well as in the wake of other developments."
Consequently, XenoPort is now suffering from Restless Investor Syndrome - its shares are down a whopping 67% in midday trading to about $6.54 on nearly 10 times normal trading volume. Given these events, Bennett has to be sorry Horizant isn't already available to treat migraines.
Comments? Email the author at windhover-dc@windhover.com
Saturday, February 20 2010
Due to the extreme weather conditions in the Washington, DC metro area, FDA was closed from February 8-February 11. In addition, the building at FDA’s White Oak campus that houses most of the new drug review staff for FDA’s Center for Drug Evaluation and Research (CDER) as well as the CDER document room was closed for an additional day on February 12 due to emergency building maintenance.
Because of the closures, FDA has “put procedures in place” to manage Prescription Drug User Fee Act (PDUFA) goals that “came due during, or are coming due soon after,” the closures, the agency said. Medical Device User Fee Act (MDUFA) goals are impacted as well.
The procedures apply to all PDUFA goals, according to FDA, including: the review of Investigational New Drug applications (IND), New Drug Applications (NDA), Biologics License Applications (BLA), and supplemental applications to NDAs and BLAs.
For PDUFA goals that came due during the week of February 8, 2010, or the week of February 15, 2010, FDA extended the goals for up to 5 business days.
For PDUFA goals that are coming due February 22, 2010, and beyond, the FDA will “assess the practicality of meeting the goal and will extend the goal as needed.” The agency claims the extension will not go beyond the five days it missed due to the severe weather.
FDA does not expect user fee goals for all applications currently under review will be extended. Applications “further in the future” will not require an extension, according to the agency.
The agency notes all submissions that were sent to FDA and would have normally been received during the closure may not be marked as “received”, for purposes of calculating any review or regulatory clocks, until the FDA center to which the submission was sent resumes its document receiving services.
The slight delay will inject an added layer of uncertainty around timing of decisions on applications for the first half of the year.
In addition, there are a number of applications pending at FDA that are already past their user fee deadlines; those applications may be further delayed as FDA prioritizes catching up on applications that can still meet their deadline.
Comments? Email the author at windhover-dc@windhover.com
Sunday, February 14 2010
The sense of uncertainty surrounding the impact of health care reform on the biopharmaceutical industry just went up with the news that Pharmaceutical Research & Manufacturers of America CEO Billy Tauzin will step down at the end of June.
The timing of Tauzin's departure should have been perfect. If health care reform had made it through as planned ahead of President's Day, now would be the perfect time for Tauzin to take a bow and leave the implementation to his successor. After all, Tauzin is 66, he has been with the association for just over five years--and is also past the five-year milestone in his recovery from intestinal cancer. If only health care reform was done, it would all seem so right.
But health care reform, to put it mildly, is in a state of flux, and so is PhRMA’s famous (or is it infamous?) $80 billion dollar deal for health care reform (or was it a $90 billion dollar deal, or more?).
As it happened, the timing of the announcement (late in the evening on a snowbound week in Washington) took a lot of people by surprise.
So naturally, everyone is wondering the same thing: Are things about to get REALLY bad for Big Pharma?
There are certainly good reasons to worry. First, as we pointed out here, the Democratic leadership appears to be convinced that one of the critical factors in the sour public mood for reform is frustration with the process—and, at least among some prominent Democrats, the PhRMA deal is a case in point.
And its not like Republicans are any happier with the PhRMA deal. Indeed, we are hearing something close to glee at the prospect that the industry will be asked to make the $80 billion contribution to fund other priorities before the year is through.
No question. It could get ugly. But it is far too soon to press the panic button.
Right now, no one can say for sure what will happen on health care reform. It is still possible that a bill very close to the one that looked ready to move in mid-January can make it into law. Failing that, big things could still move through Congress: things like filling in the Medicare Part D donut hole, follow-on biologics legislation, or health insurance reforms that would make expensive drugs more affordable for many people.
What Tauzin’s announcement does is give PhRMA flexibility: if things go well, they can keep the deal, either by working through the last steps of the process during Tauzin’s final months, or by sticking with it under his successor. And they can do so while fending off critics who claim it was a sweetheart deal all along: after all, the guy who cut the deal is out of a job, right?
On the other hand, Tauzin’s departure makes it much easier to turn to a scorched earth strategy if it comes to that. If the focus shifts from reform to punitive taxes, new rebates, populist measures like reimportation and price negotiation, then PhRMA will find it much easier to just declare the deal dead and take the gloves off in return.
We do think, however, that it’s a shame about the timing. Tauzin’s five plus years at PhRMA were a remarkable time, with the association pulling off the nearly impossible feat of transitioning from a quintessentially Republican organization into one that, if anything, may find itself too closely aligned with the suddenly not unstoppable Democratic majorities in DC.
You don’t have to agree with the policy to appreciate the skill it took to pull that off, building alliances across the spectrum of advocacy organizations in DC and across the aisles in Congress.
Sure, Tauzin wasn’t perfect--in the wake of the departure announcement, we’ve heard the rumbling that he didn’t focus enough on the details to translate the framework of “the deal” into the fine print that would make it work.
But we’d bet anything that PhRMA would be much worse off today if he hadn’t built bridges with organized labor, universal coverage advocates and other groups that don’t always see eye-to-eye with Big Pharma.
And we can honestly say that, while we know plenty of people who don’t agree with Tauzin’s positions, we’ve never met anyone who didn’t like him personally.
Those will be some pretty big shoes to fill. And in our next post, we’ll offer our thoughts on who PhRMA might pick to try….
Comments? Email the author at windhover-dc@windhover.com
Sunday, February 14 2010
PhRMA CEO Billy Tauzin is stepping down at the end of June. We pointed out in our first post that he leaves some pretty big shoes to fill--so, naturally, we want to do our part to help.
We’ve come up with a list of 12 potential replacements for Tauzin. But before we tell you who they are, we should also say that we bet none of them gets the job.
Yeah, our tongue is firmly in our cheek on some of the candidates. But more importantly, we bet PhRMA will go in a different direction this time and look for someone with a lower profile than Tauzin (or almost any of the potential replacements we suggest).
PhRMA has traditionally preferred a leader who is not a nationally known political figure, someone with specific expertise in critical areas. Before Tauzin, its two heads were IP attorney Gerry Mossinghoff and international trade lawyer Alan Holmer.
In part that’s because PhRMA’s members recognize that, while national politics dominates the headlines, their business is built on the fine points of intellectual property, regulatory nuance and complex pricing/reimbursement policy.
But it is also because—let’s face it—Big Pharma CEOs don’t want someone telling them what to do. They decided last time around to get over it: Tauzin was hired to lead the board, and that’s what he did. But we’re betting the PhRMA board isn’t going to look to be led again any time soon.
Still, we can’t help imagining different national figures who might help PhRMA improve or adjust its position in Washington, and so offer you the follow list of possible candidates for the top job at the trade association….
Former Senate Majority leader Tom Daschle: Why not go all in on the Health Care reform deal by hiring the man who was supposed to run health care reform in the White House? Just don't forget to pay the driver!
Connecticut Democratic Sen. Chris Dodd: Probably the biggest name PhRMA could go after among current Dems in Congress. Dodd is retiring rather than face a tough reelection battle, and has a good relationship with Pfizer, a big Connecticut employer.
Pennsylvania Sen. Arlen Specter: He hasn’t been a Democrat for long, having pulled a Billy-Tauzin-in-reverse and changed parties last year. Pennsylvania is a big pharma state, and Specter has a strong record in support of R&D and intellectual property.
Richard Gephardt: The former House Democratic leader has done a lot of work with PhRMA on issues like supporting science in America. He also has pull with the labor unions. He’d be great--at least until November.
A health system CEO: Glenn Steele (Geisinger) and Dan Cortese (Mayo) both got consideration as potential heads of the Centers for Medicare and Mediciad Services because their respective institutions are viewed as models of innovative payment and delivery networks. Selecting someone like that would show PhRMA is serious about delivery reform in health care.
Biotechnology Industry Organization CEO Jim Greenwood: PhRMA lost a big member when Roche acquired Genentech and decided to follow Genentech’s decision to maintain a membership in BIO only. Since then, PhRMA has stepped up longstanding efforts to recruit smaller companies--even modifying its tagline in ads to brand itself as “America’s pharmaceutical and biotechnology research companies.” And its biggest members have been steadily bioteching themselves. So why not just merge the two groups?
America’s Health Insurance Plans CEO Karen Ignagni: If Tauzin’s health reform dealmaking is the problem, then Ignagni's refusal to deal must make her the solution. Plus she’s shown a Tauzin-like political flexibility, having once been a single-payor advocate before taking the reins of the group most committed to protecting private health insurance in the US.
Bill Thomas: Too many Democrats? Then why not tack Republican. The long-time Ways & Means Committee Chairman was the key architect of Medicare Part D-- which may be all the health reform PhRMA needs (or gets) in the end. Downside: Amgen would quit the association right away. (Or is that an upside?)
Former HHS Secretary Michael Leavitt: The former head of HHS under George W. Bush is a well respected former governor who has pull with his old constituency, a definite advantage over other candidates who would have that missing from their resumes. Leavitt has long held that you can’t have health reform without Medicare reform.
Mark McClellan: While we’re on the subject of former Bushies and skilled candidates who could play both sides of the aisle, how about former FDA Commissioner, former CMS Administrator, former Clinton Administration health economist, and current head of the Engelberg Center for Health Care Reform Mark McClellan. McClellan implemented Part D and would be the kind of detail-oriented CEO that Tauzin was not.
Former Senator John Breaux: He lost out to Tauzin the first time around for the PhRMA job, how’s about a second go around? He’s a moderate Democrat with friends all over Washington.
Maine Republican Senator Olympia Snowe: Give us the 60th vote for health reform and we will give you Tauzin’s old job! That would never happen…would it?
Comments? Email the author at windhover-dc@windhover.com
Sunday, February 14 2010
The blizzard of 2010 tamped down the attendance during the annual Academy Health meeting in Washington DC February 8.
Attendance was about half of what it would have been after what serious weather professionals called a “paralyzing snowstorm” that dumped 20-30 inches in the DC metro area. The snow was so bad that everyone was surprised even half the crowd showed up. Health policy is clearly still a hot topic in Washington despite the blanket of snow.
The blizzard also gave HHS Secretary Kathleen Sebelius a perfect analogy to kick off a discussion of the status of health care reform during her opening keynote.
She complimented the organizers for staying the course, saying she had sympathy for those who work hard for months on end to put together a large and important endeavor—only to have 30 inches of snow fall the day before the meeting is scheduled: “Kind of the like the Massachusetts Senate election and health care reform.”
Sebelius noted the value of taking a moment to regroup, reconsider—and then made the case for pushing ahead. “I am confident there will be a comprehensive health care reform bill” signed into law this year, she predicted.
Sebelius did not extend the analogy any further, but we will. Blame the cabin fever if you must, but here is our list of nine ways that reviving health care reform is like digging out after a blizzard.
(1) Digging out is hard work: Our aching backs can testify to that, as can everyone on Capitol Hill, in the White House, and in the assorted lobbying operations on K Street as they try to figure out how to muster enough votes somewhere, somehow to get a health care bill through.
Sebelius noted that fact by repeating Obama’s comments from the State of the Union address that the Administration didn’t take on health care reform because it was easy. Republican Hill staff the second day read the most recent polling data, suggesting that the portion of the population who likes the pending bill is 15%-20% less than the portion who disapprove.
It is not going to be easy to get this done.
(2) Piecemeal Approaches Don’t Work: Plowing half a street does no one any good. (Are you listening, DC government?) Similarly, Sebelius made clear that ideas for piecemeal reform aren't going to fly. The President remains “as committed to comprehensive reform as ever,” she said. As a practical matter, you can’t cherry-pick reform: “the pieces are too intertwined.”
For example, Sebelius said, it is disingenuous at best to support health insurance reform without also supporting some form of mandate to prevent adverse selection.
Hill staff said the same thing (at least on the Democratic side): the pieces of reform are too interdependant to tease apart.
Republicans remain game to try—but they probably won’t get their chance this year.
(3) Getting around takes fancy footwork: Lot’s of twisted ankles and bumps and bruises in DC; avoiding a spill takes the grace of a ballerina and the balance of gymnast. Same with passing a comprehensive health bill at this point.
Here is the pathway people are currently talking about:
Step 1: The House passes a bill intended to fix the Senate bill. (Under the Constitution the House must originate all spending bills.)
Step 2: The Senate passes the fix-it bill via the reconciliation process. (Only 50 votes needed, but provisions must have budgetary impact—no policy fixes allowed!)
Step 3: The House then passes the Senate comprehensive reform bill already passed by the Senate on Christmas Eve.
Step 4: The President signs the comprehensive bill first, then the fix-it bill. The order is key: that way the fix-its replace the Senate’s language, even though the fix it passes first.
Simple, right?
(4) Snow Days Can Bring People Together: There is nothing like walking down the center of Connecticut Avenue with dozens of neighbors desperately seeking an open Starbucks to build a sense of community. While we haven’t seen a similar spirit of comity follow the Massachusetts election result, it isn’t for lack of trying (or at least trying to look like you are trying). Obama’s latest initiative is to invite the Republicans to a White House summit to exchange ideas on February 25. Hey, maybe we can all get along.
(5) Sunshine Helps: That has always been DC’s default snow emergency plan. In health care reform, it means the Feb. 25 meeting will be televised. That may help, at least as Sebelius sees it. While Americans may be “sometimes disgusted” by the legislative process, most, Sebelius says, support the “common elements” of the House and Senate bills (though she didn’t elaborate on exactly what those elements are). Perhaps a televised event focused on the substance of the bills will help re-energize reform.
Oh, and by the way, the summit is supposed to be Feb. 25, coincidentally the same day we will be discussing the impact of health care reform on business development during BIO/Windhover’s Pharmaceutical Strategic Outlook conference in New York City. We are far too humble to suggest which will be a more valuable way for you to spend your time—but its not too late to register for PSO…
(6) Goodwill Only Goes So Far: Based on DC’s experience, we now believe the Hatfield/McCoy feud was triggered when a Hatfield parked in a spot previously shoveled out by a McCoy. It gets ugly fast. Same with this summit idea. Sebelius stressed that the goal of White House meeting is not to start over on reform.
Which kind of begs the question of what is the goal. We offer one theory in The RPM Report: It is an attempt to apply a trick Obama learned on the campaign trail.
Sebelius certainly did little to undercut Republican suspicions that the goal is just to make them look bad. Obama wants to discuss ideas with the Republicans, she said, adding in almost the same breath: “It is not acceptable that half of the legislative body pushed away from the table” rather than negotiate a bipartisan bill.
Republicans, of course, see it differently, with their leadership suggesting that it is exclusion by the White House that led to an all-Democratic bill.
Sebelius did make one point that could resonate in the months ahead. “For a long time,” she observed, “the so-called public option was the issue,” with many in Congress saying they couldn’t support a bill with that included. “As far as I can tell, the public option is no longer part of the legislation,” she added, “but no one came back to the table.”
Which leads to our next point:
(7) Snow(e) Isn’t All Bad: As the path to reviving health care reform continues, it is worth remembering that there is one Republican who voted for one of the bills: Maine’s Senator Olympia Snowe voted in favor of the Finance Committee bill, though she joined all her GOP colleagues in opposing the version of the bill that came to the Senate floor. If the bipartisan revival works, it will almost have to involve Snowe.
(8) There is More Snow in the Forecast: Literally true for DC—another huge dump of snow on Feb. 9-10 followed the close of the Academy health meeting. Sebelius joked about the next snowfall at the end of her talk—using it to invite the assembled crowd to stay engaged on health policy in the weeks, months and years ahead. Metaphorically, we know that there are bound to be yet more wrinkles in this process before it finally ends, one way or the other.
But it will end. After all…
(9) Spring Will Come...Eventually: Right now we understand the hope is to revive the process and get a bill to the President before Easter recess.
Maybe I will be able to see my driveway by then...
Comments? Email the author at windhover-dc@windhover.com
Sunday, February 14 2010
The UK cost-effectiveness watchdog NICE delivered a resounding "no" to the use on the National Health Service of Bristol's dasatinib (Sprycel) and Novartis' nilotinib (Tasigna) in chronic myeloid leukemia patients intolerant to imatinib (Glivec).
"The evidence available to support [the clinical effectiveness] of dasatinib and nilotinib was very poor," declared Professor Peter Littlejohns, clinical and public health director at NICE. "The drugs' cost is also very high," he added, in a Feb. 9 press release announcing the latest draft guidance.
Sprycel costs about £30,477 per year, and nilotinib about £31,711, according to appraisal documents on NICE's website. And the drugs are taken for several years, with no evidence-based 'cut-off' point currently in use.
It doesn't even look as if the drugs came close, in other words. And Bristol and Novartis can't even consider one of the loopholes now available to companies, the end-of-life guidance issued in late-2008, which permits a somewhat higher cost-per-QALY (quality-adjusted life year) than usual for drugs that extend life in niche yet terminal diseases. (This, you will recall, is what allowed Celgene's multiple myeloma drug Revlimid to slip past the agency.)
The available evidence on the drugs' extension of life--typically required to be of at least three months--"is too weak", declares the NICE PR in yet another blow to the products' manufacturers. That the drugs, both second-generation tyrosine kinase inhibitors, offer such an extension, documents declare, "is plausible, but definitely not proven."
But at the end of this rather damning announcement came an olive branch. "It would be heartening to hear that pharmaceutical company manufacturers are prepared to share some of the very high cost of these drugs with the NHS," suggested Littlejohns.
Now if that isn't a call for a cost-share (or should we say 'patient-access') scheme, then I don't know what is. Recall that such schemes have allowed NICE to green-light a good handful of expensive drugs that likely would not have otherwise made the cut--including most recently UCB's RA drug certolizumab (Cimzia). (Interestingly, although Celgene also put forward such a plan for Revlimid, this wasn't what tipped the decision in its favor.)
So we understand NICE's call for companies to make an effort on the cost-share front--indeed, the agency's CEO Andrew Dillon has told us clearly that he'd prefer if manufacturers simply submitted such schemes up front rather than waiting for a rejection in order to fish one out.
But is Littlejohns implying that a cost-share proposal would simply eliminate all the problems that the appraisal committee identified in the submission, around trial data and design? These seemed considerable: no studies submitted assessed either drug against relevant comparator; trials were “heterogenous in terms of design, population, implementation and analysis”.
We put this question to NICE. Their reply:
Although there is some evidence to suggest that dasatinib and nilotinib could be considered clinically effective in cases of chronic myeloid leukaemia (CML), the quality of that evidence was extremely poor. This, coupled with the very high cost of the drugs, meant that the independent appraisal committee could not recommend them as an appropriate use of NHS resources.
During the public consultation on the draft recommendations manufacturers will have the opportunity to propose a patient access scheme, to make it easier for the NHS to afford expensive new treatments. We would be happy to look at such a scheme.
The answer is still not entirely clear (to us anyway). But it sure looks as if patient access schemes will trump poor data.
If that's true, we're not sure that will do anyone any good--the NHS (paying, if a reduced price, for drugs that aren't effective), companies (forced to submit access schemes above all else), or patients (potentially receiving an ineffective drug and, as a group, perhaps not getting something else as a result).
We hope, then, that we're wrong.
Comments? Email the author at windhover-dc@windhover.com
Monday, February 08 2010
Super Bowl Sunday brought a few surprises, including a nationally televised invitation from President Obama for Republicans to join Democrats for a health care summit later this month.
Obama invited Republicans to a half-day health care summit on Feb. 25 during an interview with Katie Couric on CBS. You can watch the full interview by clicking here.
The President says he wants Republicans to bring their “best ideas” on how to improve access and quality while lowering costs in the US health care system. And he’s going to put the whole event on TV.
Is the White House going to start over on health reform? No, according to Obama.
Is the focus for 2010 going to be jobs or health care? Jobs, says Obama.
Will a half-day summit on health reform cause Democrats and Republicans to come together and pass major bi-partisan legislation in Congress? Unlikely.
So why is the White House putting together a bipartisan summit on the one issue where Republicans have been remarkably successful in their opposition?
In short, it could be a trap.
It wouldn’t be the first time Obama and his team of advisors have used political theater to create a strategic advantage. In fact, Obama’s team could draw on past experience during the Presidential campaign in 2008 during the bank bailout.
In an excerpt from Henry Paulson’s book “On the Brink” published in the Wall Street Journal, the former Treasury Secretary detailed how the Obama campaign deftly managed a surprise move by Republican nominee John McCain to suspend his campaign and come back to Washington in late-September to deal with the $700 billion Troubled Asset Relief Program (TARP) and the financial crisis.
Paulson writes: “We'd devised TARP to save the financial system. Now it had become all about politics—presidential politics. I wondered what McCain could have been thinking. Calling a meeting like this when we didn't have a deal was playing with dynamite.”
McCain’s decision precipitated a meeting with then-President George W. Bush, Obama, McCain and leadership from both sides of the aisle at the White House.
Bush, according to Paulson, called for bipartisanship and the need to act quickly on the TARP legislation. Then the President called on the Speaker of the House Nancy Pelosi. “When Nancy Pelosi spoke, it was clear the Democrats had done their homework and had planned a skillful response for McCain,” according to Paulson.
Pelosi turned to Obama and said the Democratic nominee would represent the Democrats, Paulson writes. Obama proceeded to give a broad outline of the party’s strategy and emphasized that action needed to be made rapidly, while noting Democrats had been working with Paulson on a plan, including restrictions on executive compensation as a priority.
“Then he sprang the trap that the Democrats had set: ‘Yesterday, Senator McCain and I issued a joint statement, saying in one voice that this is no time to be playing politics. And on the way here, we were on the brink of a deal. Now, there are those who think we should start from scratch. ... If we are indeed starting over, the consequences could well be severe.’”
But, of course, there was no deal yet. [Rep. Spencer] Bachus [R., Ala.] had been maneuvered into giving credibility to the appearance of one. But he, [House Minority Leader John] Boehner and [Senate Minority Leader Mitch] McConnell had since issued statements disclaiming the idea that there ever had been a deal. Now Obama and the Democrats were skillfully setting up the story line that McCain's intervention had polarized the situation and that Republicans were walking away from an agreement. It was brilliant political theater that was about to degenerate into farce. Skipping protocol, the president turned to McCain to offer him a chance to respond: ‘I think it's fair that I give you the chance to speak next.’
But McCain demurred. ‘I'll wait my turn,’ he said. It was an incredible moment, in every sense. This was supposed to be McCain's meeting—he'd called it, not the president, who had simply accommodated the Republican candidate's wishes. Now it looked as if McCain had no plan at all—his idea had been to suspend his campaign and summon us all to this meeting.
Obama may be trying to repeat the TARP theatrics with the health care summit. For Obama the summit has little downside: (1) It forces Republicans to deliver a serious health reform plan; (2) It takes the health care focus off Democrats and puts it squarely on Republicans; and (3) It presents the danger to Republicans as being portrayed as obstructionists.
For Democrats, the negative impact of health care reform has already been felt. The coming health care summit likely represents the beginning of a final strategy for Democrats to take one last shot at passing comprehensive legislation this year and almost certainly not a genuine attempt at a bipartisan compromise. The chances of passage remain, however, hit or miss.
Comments? Email the author at windhover-dc@windhover.com
Monday, February 08 2010
Past import compliance violations by manufacturers will serve as a key factor in determining inspection priorities under a new program being spearheaded by FDA to ensure safety of the food and drug supply entering the country.
In addition to repeat violators, the system also flags higher-risk products coming into the country. FDA Commissioner Margaret Hamburg cited counterfeit drugs a key piece being targeted by the initiative.
The new program is rooted in an information technology system called PREDICT (Predictive Risk-based Evaluation for Dynamic Import Compliance Targeting); the technology was developed by NTELX.
PREDICT uses a variety of assessments to rank import shipments. It considers everything from whether a product is intrinsically risky to information acquired from previous examinations of shippers or producers, including past violations. PREDICT will also use information on market conditions and weather, which might suggest products that are tainted in some way. All factors add up to a risk score, and imports with the highest scores will be prioritized first.
“We expect PREDICT to offer two major benefits to FDA inspectors, to importers and to the public,” Hamburg said on February 4 at the Center for Strategic and International Studies meeting where the new program was unveiled. “First, the system will automatically flag potentially risky shipments. Second, the system will give lower risk scores to more innocuous materials, which can then be cleared through FDA inspection rapidly. This allows FDA inspectors to spend their time looking at the highest risk items. It also means that carefully labeled products with good histories will be held for shorter periods, and that is better for everyone.”
Drug counterfeiting is an important issue for large brand manufacturers as evidenced by industry stakeholders who attended the CSIS meeting.
Hamburg emphasized that drug counterfeiting requires constant vigilance by agency inspectors and the problem is greatest where drugs are coming in from developing countries where regulatory oversight is weakest. “Studies in some countries suggest that between 30 and 50
percent of certain available drugs are counterfeit,” Hamburg said.
“Needless to say, this is devastating to health and safety.”
Hamburg noted that FDA has roughly 500 inspectors for the approximately 20 mil. shipments of products that come into the US. She added that only about 8% of foreign drug facilities have been inspected by an FDA official.
PREDICT was successfully piloted in Los Angeles and is currently being rolled out in New York. The program is planned to be used in the rest of the country this spring.
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Monday, February 08 2010
The Agency for Health Care Research & Quality (the US government's de facto comparative effectiveness research center) is slowly but surely funneling out its portion of the $1.1 billion in stimulus money set aside for comparative effectiveness research last year.
Remember the stimulus money? It is supposed to be a down payment on health care reform--though lately it looks more and more like it may BE health care reform, for now at least.
Among the recent announcements, this one caught our eye: a request for bids to create a "horizon scanning system" for the agency.
No, this isn't some fancy pair of binoculars. AHRQ defines horizon scanning as "(1) the identification and monitoring of new and evolving healthcare interventions that are purported to or may hold potential to diagnose, treat or otherwise manage a particular condition; and (2) an analysis of the relevant healthcare context and landscape in which these new and evolving interventions exist in order to understand their potential impact on clinical care, the healthcare system, patient outcomes and costs."
The goal of the project is to "provide AHRQ with a systematic process to identify and monitor healthcare technologies that are likely to have a high clinical, system and cost impact in the US."
In other words, what is in the pipeline that we need to know about today to make sure that our comparative effectiveness research anticipates innovative technology.
This is a pretty big deal, if AHRQ can pull it off. The agency's director, Carolyn Clancy, explained the idea during The RPM Report's FDA/CMS Summit in December. "What I find amazing is that no developed country has figured out how to do this well, so we are going to try to build a science in this area."
The goal of horizon scanning is not "academic navel gazing," she stressed. Rather, the agency wants "to anticipate what is on the horizon in the next three to five years and what kinds of questions might we be working to understand, even before the product is on the market, which patients are likely to benefit."
That may sound scary to some: Will the federal government be working to restrain uptake of new technology? It may also sound like an opportunity: if you have a breakthrough that truly transforms a treatment paradigm, maybe the feds will become champions for early adoption. For Clancy, it is the latter: This is "not intended in any way to discourage innovation," she told the FDA/CMS Summit. "Quite the reverse."
Whether horizon scanning is a threat, an opportunity, neither or both, we can't say for sure yet. But this we do know: if you aren't building comparative effectiveness research into your drug development plan, the federal government will try to do it for you.
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Saturday, January 30 2010
We said we had a sense of deja vu going into the State of the Union, but this is ridiculous.
Last night, President Barack Obama devoted 516 words to his call to finish work on health care reform, about five minutes of the talk. That is about 7.2% of the total 7, 127 State of the Union address he delivered. Remarkably, it is exactly the same portion of the speech that he devoted to health care in his first address to Congress 11 months ago (427 out of 5,923 words, if you are keeping score.)
And it is about half the percentage that health care represents of the economy.
Stirring though the words may have been, their relative dearth suggests health care is hardly a make-or-break issue for 2010.
All of which means, Big Pharma has to think seriously about the consequences if Obamacare goes away.
Yes, it has reached the point where the US brandname pharmaceutical industry is hoping against hope that it can get someone to take $80 billion.
The famous deal between the Pharmaceutical Research & Manufacturers of America and the White House, which we dubbed "dollars for donuts," is up in the air, just like everything else related to health care reform.
AstraZeneca CEO and PhRMA board Chairman David Brennan made that clear at a press conference today tied to the company's year-end financial report. To Brennan's credit, he has said all along that the prospects for reform are uncertain, and today he underscored that things are more uncertain than ever.
And, in case there is any doubt, the collapse of health care reform would be a bad thing for Big Pharma. It is not just what won't happen--no bolus of newly insured customers, no filling in of the donut hole, no reduction in cost-sharing for existing insured, no new IP protection for biological therapies.
It is also what will happen. It is not like Pharma will just get to keep its $80 billion.
To us, the most important words for industry in the entire address weren't in the health care section at all, but earlier--when Obama called on Congress to tax overseas earnings. A year ago, Obama wanted to use that idea as a way to pay for health care reform, and that--maybe more than anything else--explains the deal PhRMA struck with the Administration. Industry came to the table, and the tax deferral on overseas earnings was taken off of it.
Not any more.
"To encourage these and other businesses to stay within our borders," Obama said last night, "it's time to finally slash the tax breaks for companies that ship our jobs overseas and give those tax breaks to companies that create jobs in the United States of America."
It took just 42 words to express that thought. But those are the words that could really count.
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Saturday, January 30 2010
Approval at last! But there are a few caveats. First, a black box warning for the once-daily GLP-1 analog which includes a potential increased risk of thyroid cancer (despite Novo Nordisk's repeated claims that this applies only to rodents, not monkeys or humans). Second, no first-line usage allowed. Third, significant post-approval requirements, including a CV safety study, a 5-year epidemiological study to evaluate thyroid cancer risks, a 15-year cancer registry to monitor thyroid cancer cases, and a REMS.
As such, "it's a worst case label for the product," concluded Sam Fazeli, an analyst at Piper Jaffray in London. "Bittersweet" was how Jefferies' Jeffrey Holford put it, while Citigroup simply cut to the chase with "Commercial success far from certain."
Things could have been still bleaker, though. At least the US approval has finally happened (the drug was filed in May 2008). It might have been pushed out significantly further, given the regulators' apparent problem with the thyroid cancer risk. And on the up-side, there's no need for calcitonin monitoring during Victoza therapy (calcitonin is the marker used in humans for thyroid cancer) and there are no broad contra-indications for the drug. Only patients with a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome, aren't allowed Victoza--and both those indications are very rare.
As such, Novo's management was upbeat during the analyst call announcing the news. The REMS is very remiscent of that recently imposed on Lilly/Amylin's twice-daily GLP-1 analog Byetta, said EVP & CSO Mads Thomsen, and certainly manageable. He added that many diabetes drugs (metformin, the sulphonylureas) have black box warnings, and most new products aren't awarded first-line treatment at their first pass at FDA. Thus, "we're perfectly happy with our monotherapy label," he said. (The product was denied approval as a monotherapy in Europe).
There a big 'but', though--and it's Byetta. That product has not only a five-year head start, but also hasn't got a black box, hasn't got a thyroid cancer risk warning, can be used as an initial therapy, and thus remains "first choice" treatment in this class, according to Fazeli, despite its more frequent administration.
This explains the generally (although not exclusively) down-beat analyst reaction to the news; "we see more room for disappointment than surprise on Victoza," writes Citigroup's Mark Dainty. Never mind the fact that Victoza outperformed Byetta in blood sugar lowering in a recent Phase III head-to-head trial.
Novo's management still thinks it can surprise, however. (They're a confident lot.) They re-iterated their forecasts that Victoza will reach sales of over $1 billion by 2015 (Byetta's currently at about $700 million and it has been on the US market since 2005).
Much will depend on whether follow-on GLP-1 analogs including long-acting Byetta (EQW) and Roche/Ipsen's taspoglutide are stamped with the same thyroid cancer warnings as Victoza. (Amylin's epidemiological study of Byetta is due March 31). Novo's Thomsen is adamant that the thyroid cancer signal seen among rodents is a class-effect among the long-acting GLP-1 analogs, and points to a forthcoming peer-reviewed scientific paper outlining what he claims is a similar pre-clinical effect on thyroid c-cells for Victoza, long-acting Byetta and taspoglutide. "We'll have to live with the notion that long-acting GLP-1 analogs cause c-cell proliferation in rodents," he told The In Vivo Blog. "But there's no reason to believe that these findings have any relevance to higher species," he added.
Whether or not the other long-acting GLP-1s get the same treatment, FDA is unlikely to remove Victoza's black box for several years at least, likely until the 5-year follow-up cancer study data is available.
Meanwhile, though, with its already-expanded US sales force and pricing in line with Byetta at about $8/day for the 1.2mg dose, Novo will be pushing Victoza with all its might and leveraging its wider diabetes franchise where possible. And let's not forget the fundamentals: Victoza is once-daily, can be taken anytime, prompts some weight loss, isn't associated with hypoglycemia or significant nausea, and is relatively easy to titrate.
Those elements may yet trump the worries about cancer in rats.
Comments? Email the author at windhover-dc@windhover.com
Monday, January 25 2010
It is a funny thing: it feels like everything has changed in health care reform, and yet we can’t help but have this crazy sense of déjà vu on the ever of President Obama’s State of the Union Address.
The questions about health care reform today aren’t so different than they were eleven months ago, when President Obama made his first address to a joint session of Congress Feb. 24. (That address was not, technically, a State of the Union address, but—with apologies to constitutional scholar—that is a distinction without a difference).
A year ago, the big question was: how aggressively would Obama pitch health care reform on his agenda? Where would it fall amid other priorities, most pressingly job creation and the reeling economy? And would he say enough to bring Congress with him for the heavy lifting reform would entail?
That pretty much sounds like what we will be listening for now.
Yeah, the circumstances look very different. Then, Obama was the newly elected President riding high on an unprecedented wave of hope if not hype. Today, he is still personally popular, but his policy agenda is bloody and bruised.
On health care, sweeping legislation passed both the House and the Senate, but the election of Republican Scott Brown as the new Massachusetts Senator makes final enactment seem like an insurmountable challenge.
But things really aren’t so different than they were a year ago. In 2009, Obama addressed Congress without a filibuster-proof majority. At the time, in fact, the Democratic caucus had only 58 members: it wasn’t until Arlen Specter switched parties and Al Franken was finally certified as the winner in Minnesota that the Dems had 60.
And Obama was fresh off an embarrassing setback then too: the withdrawal of Tom Daschle from consideration as HHS Secretary and health care reform czar.
A year ago, the question was how far and how fast should Obama push for reform? Would it be comprehensive reform or bust? Or would there be a more measured, scaled down plan, with jobs, energy and other priorities defining the agenda?
Those are the same questions Democrats and health care reform advocates are asking today.
And it is interesting to remember the answer a year ago. Then, Obama announced a “down payment” on health care reform, but declined to define comprehensive reform as the priority—instead saying that a robust, sustainable economic recovery depended on reforming health care, clean energy and education reform.
We will see if maybe Obama decides he was right all along…
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Friday, January 22 2010
Our understanding is that Geisinger CEO Glenn Steele will be nominated as the next Administrator of the Centers for Medicare and Medicaid Services.
Last year, Steele was considered a top candidate for the job considering how he has shepherded the Pennsylvania-based health system using innovative payment models to lower costs and improve quality.
The Administration did not move forward with any nomination in 2009, hoping to complete work on health care reform before subjecting a nominee to the confirmation process. The final vetting of a nominee at this time would be logical.
Steele is reportedly going through the vetting process at present, and his name could be forwarded to Congress at any time.
However, it’s important to note that because of the unpredictability of health reform, the situation and Steele’s nomination, could change at any time.
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Thursday, January 21 2010
The one thing everyone agreed on when this round of health care reform began is that the status quo is no longer an option.
Remember when Pharmaceutical Research & Manufacturers of America CEO Billy Tauzin stood side-by-side with Families USA head Ron Pollack to declare that, past differences between the two groups notwithstanding, they would join forces to urge the Obama Administration to press on with health care reform?
Or America’s Health Insurance Plans CEO Karen Ignagni standing up during the White House health care summit, being called on personally by the president, to say that insurer’s would not repeat their role in blocking reform this time around?
Time and time again, we heard the same theme: in 1993-94, everyone supporting health care reform viewed the status quo as their preference if they couldn’t have reform just their way. This time it was different. The status quo was no longer an acceptable fallback.
The status quo is suddenly very much on the table.
Such is the impact of the unbelievable, unthinkable victory by Republican Scott Brown in the race for the Massachusetts Senate Seat formerly held by the late Ted Kennedy.
Sure, there are plenty of non-healthcare explanations for that outcome. Plenty of folks blame the Democratic candidate, Martha Coakley, for a less than stellar performance. And special elections are always unpredictable (we drew a comparison before between this one and the kind-of-the-same-but –exactly-the-opposite election of Harris Wofford in Pennsylvania almost 20 years ago). And Massachusetts already has universal coverage (or as close to it as any federal health care legislation would deliver).
But this is politics and symbols matter. Ted Kennedy passed the mantle to Barack Obama and made health care his legacy issue. There can be no more potent symbol of repudiation for the current reform path than the election of an avowed health care reform opponent from the opposition party to fill his seat.
That silence you hear is the stunned contemplation of all parties to the health care reform debate that the status quo might just be what they end up with after all. All those lobbyists. All those hours. All those hearings, and mark-ups, and legislative drafts, and drafts of drafts. All for nothing?
Now, as President Obama likes to say, let me be clear. As of today, less than 48 hours after it really happened, no one can say for sure what the strategy on health care reform will be. Or, indeed, whether there will even be a strategy—since it is entirely possible that the Obama Administration, House Democrats and Senate Democrats will end up pursuing different ones.
And, as we point out in “The Pink Sheet” DAILY today, there are viable options to move forward, once the dust settles—many of which still seem attractive for biopharma companies.
But whatever happens next, we expect a key element will hinge on whether the stakeholders in the debate really meant what they said a year ago. Is the status quo really not a good outcome? Because it is suddenly very much an option.
Comments? Email the author at windhover-dc@windhover.com
Saturday, January 23 2010
King will have input from an FDA advisory committee before resubmitting its immediate release oxycodone formulation Acurox¸ and the company hopes that will translate into a relatively rapid approval.
“We are anticipating an FDA advisory committee for Acurox sometime in spring, but the date has yet to be announced,” CEO Brian Markison said during an interview at the JP Morgan Health Care conference in San Francisco Jan. 13. “We think that having a successful advisory committee meeting, will help us be able to quickly resubmit the NDA.”
Acurox, which combines oxycodone with a subtherapeutic dose of niacin, is intended to discourage abuse by triggering an aversion among users who take excessive numbers of pills; someone who takes multiple doses of Acurox at once is likely to experience the unpleasant flushing reaction associated with niacin.
However, like most therapies in the opioid class, the regulatory process hasn’t been smooth. King and its development partner Acura received a “complete response” letter in July (“The Pink Sheet” July 6, 2009).
King met with FDA in September to discuss the complete response letter, and the decision to take it to an advisory committee followed. However, it does not appear that King is formally appealing the complete response letter.
FDA has tentatively scheduled a meeting of the Anesthetic and Life Support Drugs Advisory Committee April 22-23; that is the likely target date to discuss Acurox.
King expects an up-or-down vote on the approvability of the application, even though it is not technically pending for approval. The discussion is likely to focus on standards for “aversive” formulations in general: reaching agreement on how to determine whether the Acurox formulation does in fact trigger aversion, and if it does, whether it is sufficient to suggest a reduced abuse liability.
“FDA is looking for its advisors to help the agency interpret the data that will be in the resubmission,” Chief Science Officer Eric Carter explained. “Given that the science of abuse liability studies is still emerging, the division director determined that an advisory committee was the appropriate venue to review the Acurox data.”
“The expectation is that FDA will ask the advisory committee whether Acurox should be approved or not, and if the committee votes in favor of approval then the resubmission is quite honestly a relatively simple resubmission. There’s not much, and hopefully they will review it relatively quickly.”
A Big Year for King at FDA
The Acurox resubmission is only one of several important FDA-related milestones King anticipates in 2010.
The first will be approval of its launch materials for the long-acting opioid formulation Embeda, which combines morphine sulfate with naltrexone (the latter ingredient intended to block the effect of the morphine if the sustained-release pill is crushed).
Embeda was approved by FDA in August, but the company received a warning letter from the agency in response to video news releases announcing the launch. That in turn has meant a delay in rolling out a full launch campaign (“The Pink Sheet” Nov. 6, 2009).
“We met with [FDA’s Division of Drug Marketing Advertising & Communication] just before Christmas, and I think both sides fully understand each other and are taking the appropriate steps to address the issues,” Carter said.
The letter followed “a mistake on our part,” Carter added. “We let video news releases go through that we should never have approved. The materials cited…were not a deliberate attempt to mislead, and were nothing other than the result of inadvertent internal errors that we made.”
And, Markison says, the launch of Embeda is proceeding nicely, all things considered. “Despite limited materials for our field team initially, including an annotated package insert for the first two months post-approval, we have seen that the physician receptivity has been terrific, and that managed care acceptance has been quite positive. We believe now that we are in the New Year that we will see a steady build of prescription growth week over week.”
King is also planning to resubmit its application for a long-acting, abuse-resistant form of oxycodone (Remoxy), which also received a “complete response” letter at the end of 2008 (“The Pink Sheet” DAILY, July 7, 2009).
“The Remoxy resubmission is going to be a bit more voluminous than Acurox,” Markison noted. “We are excited about the way those plans are coming together. Everything remains on track. And we think that the business case for Remoxy and the value proposition remains every bit as strong as it did when we first licensed the product.”
King expects Remoxy will also go before an advisory committee in 2010.
Last but not least, King’s Carter is working on behalf of all long-acting opioid manufacturers as FDA works on developing a class-wide REMS. FDA plans another meeting on that project this spring (“The Pink Sheet” DAILY, Dec. 4, 2009).
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