Top FDA Approval Decision Gurus Weigh In on Vivus' Obesity Drug

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BOSTON (TheStreet) -- U.S. regulators have delayed by three months a decision on the approval of Vivus' obesity drug Qnexa. The new approval decision date has been moved to July 17 from April 17.

Vivus and the U.S Food and Drug Administration need the extra time to reach agreement on a risk management plan, or REMS, which will put in place safeguards and restrictions on the way the company can market and sell Qnexa.

Does the extra time requested by FDA suggest the agency is leaning towards approving Qnexa?

I've asked the top six contestants in TheStreet's 2012 FDA Drug Approval Contest to answer this very important question. These guys have racked up an impressive track record to date, so pay attention to what they say.

For the record, none of the contest leaders correctly predicted the delay in the Qnexa decision, but then only 7 of the 60 contestants overall got this one right. However, the reasons for and against Qnexa approval still apply.

@cbhwatch

Contest record to date: 12-1

Hometown: New Braunfels, Tex.

Age: 30

Occupation: Accountant, biotech investor for five years.

The secret to your FDA drug approval picking success: Blogs/articles I read from people I follow on Twitter, reading Twitter comments, reading SEC filings, and most importantly -- luck. I travel a lot for work, so in the evenings I read just about anything relating to biotech.

Your Vivus Qnexa prediction: Approval. Why? Best efficacy out of all three obesity drugs; positive Orexigen Therapeutics panel with lack of efficacy; and the REMS risk management plan for women. I'll admit I got burned on Arena Pharmaceuticals after the "hidden" rat tumor data that was brought up at the advisory panel.

Bonus question: Will FDA approve Arena Pharmaceuticals' lorcaserin on June 27? No.

Adam Burden (Twitter: @crusadernz)

Contest record to date: 11-2

Hometown: Auckland, New Zealand

Age: 33

Occupation: Secondary school (high school) teacher of economics and Japanese. Founder of BioPharmCatalyst (but that's hardly an occupation!)

The secret to your FDA drug approval picking success: I found my success was due to trusting my gut feeling and not over-complicating the process. To get this gut feeling requires many hours of hard work, skimming through every press release, 8-K and 10-Q filings released by all small-mid cap companies. It's a lot of work but after awhile you begin to develop a really good feel for each of the companies, the language they use and how open they are with investors. Also, keep an eye on companies that are filing resubmissions and those that are filing for the first time. Without a Special Protocol Assessment (SPA), a new drug applications needs to be perfect to succeed at first attempt. It's much easier the second, third time etc. Twitter helps as well. Two of my decisions were based on information from reliable tweeps.

Your Vivus Qnexa prediction:Approval. Why? If there is ever an FDA advisory panel meeting, listen to it. I listened to the Qnexa meeting live for the original PDUFA date in 2010 and distinctly remember sensing that many on the panel who voted "no" would have voted "yes" had there been more data available. Vivus produced extra data following the complete response letter so I felt comfortable, especially given the indication is not for women of child-bearing potential. I think Qnexa will eventually get approved but I'm all too aware that there is a possibility that the PDUFA date could be extended.

Bonus question: Will FDA approve Arena Pharmaceuticals' lorcaserin on June 27? No.

@biopharminvest

Contest record to date: 10-3

Hometown: Philadelphia, Penn.

Age: 41

Occupation: University faculty member, specializing in biomedical research. Before that, several years postdoctoral experience at the National Institutes of Health.

The secret to your FDA drug approval picking success: There is no "secret" in my prediction, just due diligence and knowledge in biomedical studies. With years of experience in this field, it is not hard to find the real story behind the publicly accessible clinical trial data and drug-development information. I have learned, however, that having bad or good data is not the always the sole reason for FDA's calls. I like to carefully evaluate drug safety and efficacy, then based on the overall benefit-risk assessment, predict the FDA's decision.

Your Vivus Qnexa prediction: Rejection. Why? I think there is a chance FDA rejects this drug because of the long-term safety concern. Obviously, obesity is not a life-threatening disease, so new treatments should have sound safety profile before entering the market. Qnexa is comprised of phentermine and topiramate, the latter of which is already approved for epilepsy and migraine. The long-term adverse effects of Qnexa, including cardiovascular, teratogenicity and cognitive dysfunction risk, have not been sufficiently addressed in clinical trials. Since the over-the-counter weight-loss drug Xenical is already available, Qnexa should be scrutinized for long-term risk. I also think FDA should be extremely cautious about weight-loss drug safety due to previous experience with the fenfluramine market withdrawal in 1997 due to cardiovascular risk. I stand by my prediction for a Qnexa rejection despite a positive vote from the FDA advisory panel.

Bonus question: Will FDA approve Arena Pharmaceuticals' lorcaserin on June 27? No.

Patrick Crutcher (Twitter @chasingthealpha)

Contest record to date: 10-3

Hometown: Los Angeles.

Age: 27

Occupation: Co-founder Chimera Research Group; Statistics PhD candidate at UCLA.

The secret to your FDA drug approval picking success: Keep digging until your brain is near fried, extra crispy preferred. I've been as successful as I have because I try to understand all aspects behind the drug's development from the scientific rationale to trial design. Everything with the FDA is about safety and efficacy, so you always need to put yourself in the shoes of the regulators. Additionally, it always pays to be skeptical of small-cap biotechs, especially when it comes to their statistical and manufacturing portions of their new drug applications. Too many companies try taking shortcuts that only make the path to approval longer.

Your Vivus Qnexa prediction: Approval. Why? That's the million-dollar question. Like I said, it's a balancing act between safety and efficacy in the indication. For example, the possibility of increased cardiovascular safety issues coupled with mediocre weight loss won't cut it in an indication like obesity. Without giving too much away, I think Vivus has made a great case for approval in terms of safety and efficacy, which is something neither Arena Pharmaceuticals nor Orexigen Therapeutics has done.

Bonus question: Will FDA approve Arena Pharmaceuticals' lorcaserin on June 27? No.

Paul Danese (Twitter @pdoofus)

Contest record to date: 10-3

Hometown: Glastonbury, Conn.

Age: 43

Occupation: Run a consulting business related to FDA drug safety.

The secret to your FDA drug approval picking success: Luck (lots of it) and maybe some experience. I've been investing in biotech stocks and following FDA for many years.

Your Vivus Qnexa prediction: Approval. Why? The Jan. 9, 2012 press release indicating that FDA asked Vivus to remove the childbearing-female contraindication from the proposed label was a pretty strong sign. The advisory panel vote (20-2) was strongly positive. Qnexa meets FDA's pre-specified efficacy thresholds for obesity meds. Qnexa's active ingredients are already approved.

Bonus question: Will FDA approve Arena Pharmaceuticals' lorcaserin on June 27? No.

Joseph Lee (Twitter: @fda_tracker)

Contest record to date: 10-3

Hometown: San Francisco

Age: 30

Occupation: Graduate student in Pharmaceutical Sciences and Pharmacogenomics. Founder of FDATracker.com

The secret to your FDA drug approval picking success: There is no secret, just lots of hard work. Reading primary literature (peer-reviewed journal articles, conference abstracts, published posters). Reading company press releases, SEC filings, listening to conference calls. Learning from history (what is the current FDA guidance, how has the FDA ruled on similar drugs in the past, how do they view different classes of drugs.) Discussions through Twitter and offline to hear opposing viewpoints. Putting it all together in a logical argument for my thesis, as I do on my website. And of course, some luck.

Your Vivus Qnexa prediction: Rejection. Why? A March 6 article in Circulation states: "A targeted approach would first focus on the mechanism of action of the drug. If preclinical and early clinical evidence indicates a concern that the drug may increase cardiovascular risk (as would be the case for sibutramine, phentermine/topiramate, and the naltrexone/bupropion combinations), then exposure to the drug product would need to be sufficient to rule out specific cardiovascular safety concerns."

Phentermine (increases norepinephrine levels) and buproprion (norepinephrine re-uptake inhibitor) increase blood pressure through a similar mechanism of action. Hiatt, Thomas, and Goldfine (authors, EMDAC voting members) and Colman (reviewer, FDA division director) are making an explicit comparison between the cardiovascular safety of Contrave and Qnexa.

At the March 28 obesity EMDAC, the vote was 17-6 in favor of a two-tier cardiovascular safety study even in cases where there is no cardiovascular safety signal. Additionally, EMDAC reiterated their desire for strict MACE endpoint, which has been the criteria for all diabetes cardiovascular safety trials, including Contrave's.

Contrave's cardiovascular outcomes trial requires demonstrating the upper limit of the 95% confidence interval for the MACE hazard ratio less than 2. This is similar to the diabetes guidance, which states the upper limit less than 1.8. Qnexa does not satisfy either criteria, as the upper bound for the strict MACE confidence interval is 2.64.

Qnexa's phase III trials did not accrue enough cardiovascular events to statistically rule out cardiovascular risk based on strict MACE. Logically, if FDA follows the precedent it set with the diabetes drugs and Contrave, then a pre-approval cardiovascular outcomes trial for Qnexa would be required. Arguments for approval based on the component drugs already being approved or the drugs being used off-label do not apply since they did not apply to Contrave's similar situation.

FDA is different from EMDAC. It's possible there is political pressure to approve Qnexa or FDA will be more flexible given Qnexa's efficacy. I may be relying too much on a strict interpretation of the current guidance. I certainly could be wrong, but I do not believe approval is as assured as some have suggested.

--Written by Adam Feuerstein in Boston.

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Tickers in this article: ARNA OREX VVUS