Alicia Mundy was provided with wealth of information which she either did not have time to read or ignored for unknown reasons.
Alicia transcript here for you AGAIN and decide if this needs any attention
If Dr. Kaul says the neoplasm risk really wasn’t a factor, he should watch a replay of the panel again:
Segal –
Yes
Met efficacy; met valvulopathy risk; cancer a little unsettled. Other adverse effects a non-issue. Need active surveillance, large post-approval studies, and possible registry.
Goldfine –
Y
“I found this a very very hard decision” to make. Small magnitude of weight loss relatively, but I think that can be clinically quite important. Secondary endpoints moving in the right direction are “important to me”, although concern with limited population. Suggest use in “multidisciplinary teams that counsel behavioral, lifestyle, and other factors” including any potential cancer risk issues.
Gregg –
No
“This was a very difficult vote. I think this was a promising drug. I think the weight loss, while not great, was acceptable. I thought the profile of risk factor benefits was encouraging, actually, and there wasn’t any clear evidence that this was a dangerous drug.” There was enough doubt raised about risk factors to take a harder look at benefits and magnitude of risk factors. “I think the drug is promising, but it’s not quite there yet, in terms of showing the evidence.”
Proschan –
Yes
This was also a very close vote for me… and by a small margin voted yes. I agree with the comment on secondary endpoints. “I definitely agree with the population restriction concerns and the troubling results in rats… but again, I don’t know how to translate that to humans, and I thought the evidence in people did not really raise a huge safety flag in my mind.”
Thomas –
Yes
One of the harder decisions to make… sponsor did what they were required to do, met the criteria that the FDA set forth, and to assess many of the other risks. “One reassuring thing is that, unlike some other agents, the benefits of weight loss, even though modest, did seem to correlate with what we think are important markers; blood pressure, heart rate… so I think the safety signal was better.”
Flegal –
No
“I vacillated until the last minute. I think this is a promising drug and it fills a niche. The weight loss is small—I found it encouraging, however, that actually the change in biomarkers pretty much tracked the degree of weight loss in both the treatment and the placebo arm, which suggests that that is how this is operating.” There are some unanswered questions about the risk need and the population that stands to benefit more from it. “So, on balance, I voted no, but again, it was a close call.”
Weide –
No
Most concerned about rat tumors and although the cause of cancer was identified, didn’t know how it correlates to human. “What bothered me the most was only a little more than 3% difference between the placebo and active group (average weight loss), and the limited population studied.”
Felner –
No
I have a lot of difficulty like other people on this committee. “I think the sponsor did a great job. They performed the study, they met the criteria that were asked of them; but I think when it comes down to it, I didn’t really have a lot of issues with the risk. “I think there’s “still a possibility of getting this through, from the sense of doing more pre-market studies.”
Henderson –
No
“I agree with all the comments that this is a promising drug, and I would encourage the sponsor to re-apply. I loved the quality of life data – one of my complaints when there’s not the patient perspective there.” Voted no because too much uncertainty in the rat tumor issues and of the real life population this would be used in. “I do think this is promising, but just too much uncertainty at this time.”
Douglas –
No
“I voted no because of concerns about marginal effects in a selected population, with continuing concerns for side effects. And that wasn’t completely put to rest. The argument that there isn’t much in this space and there’s an urgent patient and public need – I don’t think really mitigated the concern of putting out a drug that doesn’t do enough, and may do harm on the market.”
Kaul –
No
“I really didn’t think the current portfolio of evidence was enough to persuade me that positive benefit risk has been demonstrated. Highly selective population that is not really representative of the real world was chosen.”
Coffin –
Yes
“I voted yes, and I do want to applaud the sponsor for including… the ethnicity of the patients, and I hate to say it, but I wish they were sicker. I wish they were sicker obese people that were part of the study. That said, it did meet the requirements of the FDA. I’m not pleased about the weight loss being only 3%, and it is only 3%.”
Gardner –
No
Applauded the sponsor for diversity and looking at endpoints besides weight loss. “I think my concern is about the tumors. Was encouraged by the suggestion that there’s a way of shedding some light on this going forward. “I think that the line in the question that stopped me, in particular, was that used long-term in a population of overweight people… I’d like to get it as right as we can the first time.”
Connolly –
No
“I echo the comments of many of the individuals here. The selected population studied demonstrated modest efficacy with this medication… I was concerned about the “long-term” phrase in the question, and for that reason I felt that the potential risks outweigh the benefits.
Colman –
Final Remarks
“…I feel as though I should apologize for putting you through this, um, unpleasantness. We certainly do appreciate you and your time. And we do go back to the office and discuss… And you should just be grateful you don’t have to do this everyday for your living. I do want to thank Arena, I know they worked extremely hard, so again thanks to everyone.
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Meddy's response to poorly written WSJ article
I'd like to set one thing straight-- those of us involved in the "backlash" are not alleging "possible bias and ignorance among the FDA panel members." We are alleging a biased presentation of facts by the FDA.
The FDA presented, unexpectedly & at the last minute, a hugely exaggerated supposed cancer risk based on a fatally flawed analysis of tumors occurring in rats. Despite their intention to make cancer risk the centerpiece of their presentation, they inexcusably failed to appoint a toxologist or oncologist to the panel. Panel members expressed over & over their complete inability to assess the relevance of these rat tumors to humans. Normally these panels have the appropriate medical expertise to assess the specific issues that will be under discussion. Lorcaserin's biggest safety concern was EXPECTED to be valvular heart disease, and accordingly there were 3 cardiologist on the panel. The omission of a clinical cancer expert guaranteed that this cancer risk would not be addressed adequately during the meeting. This left a huge, scary cloud of question marks in the minds of all the panelists, which hung over the entire meeting.
Most of the panelists clearly stated, in giving the reasons for their vote, that the unresolved cancer risk was primary or predominant in their decision. It's all on tape, & it's in the transcript. If they are backing off on the cancer risk now, that's good-- several physicians sent them a detailed critique of the errors in their analysis, so they *should* back off. But apparently, to save face, they plan to fall back on the supposed "modest efficacy" of lorcaserin as their reason for voting no.
Unacceptably low efficacy is another canard promoted by the FDA throughout their presentation. Lorq's efficacy is in line with ALL OTHER SUCH AGENTS approved or reviewed in the past 12 years. Lorq did not meet the first of the two ALTERNATIVE criteria that FDA Guidelines provide to indicate evidence of sufficient efficacy. Neither did ANY OF THESE OTHER AGENTS. Lorq met the second of the FDA's two ALTERNATIVE criteria-- and it achieved it quite solidly, despite Dr.Eric Colman's denigrating remarks at the hearing.
Dr. Colman headed the FDA panel & clearly indicated he opposed lorq's approval EVEN IF THERE WERE ZERO SAFETY CONCERNS -- because of low efficacy. This is in complete contradiction to his own recorded statements when the Guidelines were being drafted-- that meeting the second criterion of categorical efficacy would establish an agent as effective. We are asking the FDA-- why is Lorqess being held to a higher standard than previous weight loss agents?
Is the answer to that question Qnexa, with its highest efficacy ever achieved? If it is, then their thinking is inexplicably muddled. Lorcaserin is a SINGLE AGENT- with the characteristic modest efficacy of almost ALL single agents. Qnexa is a DOUBLE, COMBINATION AGENT--with two drug constituents that contribute to its efficacy. It is wrong-headed to expect a single agent to have comparable efficacy. The new norm for bariatric physicians trying to help their patients is the acknowledgment that effective help will probably require a "cocktail" of drugs. Lorcaserin is a highly selective drug that targets one specific piece of the obesity puzzle. It can be combined with other anti-obesity agents to increase efficacy, just like Qnexa. It has a much better safety profile than either phentermine or topiramate, the two components of Qnexa.
Unlike Qnexa, lorcaserin is a totally new, novel weapon in the fight against the diabesity epidemic. Qnexa, in contrast, brings NOTHING NEW to the table-- it is simply a combination of two drugs, phentermine and topiramate, that are freely available, inexpensive, and already being used in combination in clinical practice. Approving Qnexa will only increase the cost of these drugs to patients who can't afford it, considering that health insurance generally doesn't cover weight loss meds.
Why would the FDA be biased against one tiny little biotech? We don't know for sure.We know that obesity is the largest unmet need in the pharmaceutical industry, with huge potential profitability.We know that Dr. Colman favors the approval of Qnexa--he as much as said so immediately after the Qnexa advisory conference back in July-- when he held an unusual, impromptu press conference to reassure Vivus investors that he was "surprised" that the panel voted against approval (since, he said, both drugs are already approved) & suggested that they were merely "hesitant," " not strongly opposed," and had only "lingering concerns."
These statements just happened to stop the free-fall of the VVUS stock price.
We know that Dr. David Orloff, former Director of the Metabolic/Endocrinology Division that reviews weight loss drugs, left the FDA in 2005 under a cloud of suspicion of "coaching" (read "biasing") another advisory committee- to approve a diabetes drug with unacceptable cardiovascular safety concerns -- on a panel where there just happened to be no cardiologist -- which led to a major FDA embarrassment when Cleveland Clinic doctors published a scathing critique -- of the biased & inadequate FDA analysis. Sound familiar? So guess where Dr. Orloff went after he left the FDA. Go ahead, just guess. He went to be Medical Director of Medpace, the Clinical Research Organization that just happened to run all of Vivus' clinical trials. Oh, and he "crafted" the NDA (New Drug Application) for Qnexa -- to be reviewed by his former close associates & subordinates. Is this even legal???
And we know that Harry Markopolos, the whistle-blower who brought down Bernie Madoff, testified before Congress that the FDA, as well as the SEC, were "captured" agencies. Meaning these agencies are no longer serving the public interest, but rather are "captured" by powerful financial & corporate interests and now serve THEIR interests.
So we don't know if the bias comes from Big Pharma, or Small Pharma, or just some shady quid pro quo. We just know there's bias.
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