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 or studied for weight loss properties in the past 20 years. This list includes sibutramine, orlistat, and rimonabant; anit-depressants fluoxetine and bupropion; and anti-epileptics topiramate and zonisamide. 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 for "Big Pharma." 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," and "not strongly opposed," and had only "lingering concerns." These statements were immediately telegraphed throughout the biopharm universe, & 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: for "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. Sounding 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 ran all of Vivus' clinical trials. Oh, and he "crafted" the NDA (New Drug Application) for Qnex--that's a quote from Vivus itself -- to be reviewed by his former close associates & subordinates. I would not have believed this was 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) was a "captured" agency -- meaning that 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.
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) was a "captured" agency -- meaning that 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.
Great summary. Needs to be sent to the journalist that follows ARNA for the San Diego Union Tribune.
ReplyDeletezino
Great summation of the bias and the differences between Lorc and Qnexa. My only slight disagreement with this excellent summary is the comments saying that the "FDA and SEC are captured agencies.
ReplyDeleteI know three people via my son who went to Law School with them, that work at the SEC and each one of has a very honorable sense of duty and are of high character and integrity. Unless you have specific examples, I think it is wrong to paint a broad brush against these agencies. Instead, I would recommend the focus be on specific individuals where there are signs/evidence of bias or possibly wrong doing.
A comment like "SEC and FDA are captured" is an insult to all of the good people that work at these agencies. Why should they be slandered with the few bad apples.
Correction to my earlier comment.
ReplyDeleteAfter rereading again, I realized that the author was quoting Markopoulos (sp) as stating that the "SEC and FDA were captured agencies." I want to apologize for my comment above that the author made that statement.
Therefore my disagreement is with Markopoulos, although that the time he made that statement, there probably was a bit more truth to it. Since his testimony, there have been numerous changes in the SEC to correct the issues that Markopolous faced in trying to get the Madoff scam investigated.
Markopoulos did not bring down Madoff, despite his best efforts (Madoff turned himself in).
ReplyDeleteMarkopoulos did prepare a detailed presentation which he gave in person to SEC staff who didn't seem to understand a word he said. The only people at SEC with any experience in finance (senior staff) are "captured" in the same manner as other agencies of government--they must be loyal politically to the administration which appointed them if they want to keep their jobs.
Saying that the SEC is captured is not an insult to the idealistic young lawyers who start their career at SEC (often to later make a bundle on Wall St. leveraging their contacts), but simply an astute observation.
The FDA is run in very much the same manner as the SEC, and observing that they also are owned by their political bosses, is fair comment.
By the way, nothing has changed at SEC that would make it any more likely today that a politically well connected crook like Madoff would be brought down by an outside whistleblower, much less an internal investigation (see the example of the SEC attorney who asked to interview John Mack, Pres. of Morgan Stanley, regarding an insider trading case and was fired immediately by the SEC after Mack complained. The SEC later settled with the staffer out of court after he sued. John Mack to this day has never been investigated about this case which is still unresolved.