Lingering Concerns about Qnexa's Safety
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Dr. Sanjay Kaul used his favorite phrase -- "Lingering concerns" -- in arguing against the safety of Lorcaserin (see "Dr. Kaul's Bias"), despite the lack of clinical evidence for his concern. The advisory committee and the FDA didn't agree with Dr. Kaul, and rightfully so. We can fervently use the same phrase to refer to Qnexa's safety concerns since there is proven clinical evidence of dangerous side effects, which are not only real, but literally lingering.
Notably, the FDA recognized the interim results from Vivus's (NASDAQ: VVUS) FORTRESS (Fetal Outcome Retrospective Topiramte Exposure Study) as preliminary because no data validation was performed on the results. Vivus promised the final FORTRESS study results in the first half of 2012, in hopes of leading the FDA to approve QNEXA. To date, however, Vivus has failed to produce these results and has recently suggested the data will be available in the third quarter 2012, several months after the Qnexa PDUFA date (July 17). The FDA and investors should be very cautious about this maneuver. How does the FDA approve Qnexa without the completion of a study?
Furthermore, Vivus' FORTRESS study has obvious flaws in the design, as pointed out by the FDA, which set the sample size for topiramate-exposed mother/baby pairs at 2,300, and 16,000 for unexposed mother/baby pairs but the study only used 1,945 and 13,614 cases for exposed and non-exposed pairs, short of FDA's mandate (the results, by the way, show that the pair exposed in the first trimester are 6.46 times more likely to be born with OC than the non exposed pairs).
These sentiments were voiced to the FDA in a letter written by a citizen who has concerns about Qnexa's safety profile. Dr. Ralph Ryback expressed his concerns over Qnexa's safety profile to the FDA in this letter.
Anita Gurak argued the FDA should issue a CRL to Vivus until the lingering concerns are resolved. Her letter can be found here.
Recognizing the lack of the promised FORTRESS study and impossibility of REMS for Qnexa's ingredients PHEN/TPM, Joseph Dedvukaj, a noted trial attorney from Bloomfield Hills, Michigan, recently filed a Citizen Petition about Qnexa's lingering safety profile and he raised serious REMS concerns with the FDA reviewers. The FDA cannot develop a REMS without knowing what the metrics are. Dedvukaj argues "even an extremely restrictive REMS will likely cause the physician and patient to take the path of least resistance and prescribe the ingredients PHEN/TPM because: 1. the ingredients are cheaper, and 2. it is easier for the physician/patient because any REMS, no matter how restrictive, will be too costly and time consuming for patients and physicians to follow."
The lingering concerns are not just around the FORTRESS study. A new research abstract published on June 12, with data from the North American AED (Anti-Epileptic Drug) Pregnancy Registry shows:
"Of the 5,667 women taking an AED as monotherapy during the first trimester, 4,899 were eligible for analysis. Five infants exposed to topiramate (1.4%) had a cleft lip; this is about 10-fold higher than expected based on any reference population (approximately 1 per 1,000 births in the general population)" (source)
"199 Newest Publications in birth defects research part a: clinical and molecular teratolog" published new data from a study titled: "Newer anticonvulsants: Lamotrigine, topiramate and gabapentin," which suggests an increased risk of oral clefts in infants exposed to topiramate, and perhaps lamotrigine, early in pregnancy, and of growth retardation for topiramate-exposed infants. Given that topiramate was the worst of the anticonvulsants tested, not only the FDA should not rush into approving Qnexa, it should revisit the labeling for topiramate.
One concern was voiced as follows:
"And there is no way they can rationalize that young women will avoid Qnexa or take it with caution or that they will be honest with their physicians in terms of addressing the child-bearing issues. A black label warning, no matter how restrictive, will not be sufficient to protect Vivus and subsequently the FDA from the potential litigation which is out there just waiting for the first birth defect to occur to a woman who took Qnexa. At that point, it will be impossible for either the manufacturer or the Federal agency to claim, 'We just didn't know how serious the threat of defects could be.'"
A variety of law firms seem to be poised to file lawsuits related to known dangerous, clinically documented side effects for users of Qnexa. Here are some links posted in social media discussions:
With a safe and effective obesity drug just approved (Arena Pharmaceuticals' (NASDAQ: ARNA) - Belviq), the FDA should not be under any pressure to rush into approving Qnexa without, at least, the completion of FORTRESS study and restrictive REMS to follow, if a REMS can be devised to prevent the ingredients from being abused by physicians/patients. Arena's Belviq is the clear winner of the obesity medicine space.
I am long ARNA. This article is not an investment advice. Please do your own research. To find out more about my interests visit www.rezamusic.com and to join my mailing list email me on (info at rezamusic dot com). The Motley Fool has no positions in the stocks mentioned above. Try any of our Foolish newsletter services free for 30 days. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy.If you have questions about this post or the Fool’s blog network, click here for information.