Only a year ago, three companies were in a tight race to be the first to bring a novel anti-obesity drug to market in years. Each one, Arena, Orexigen, Vivus, had claims of superiority, whether it be safety, novelty, or efficacy. And each one was valid. It appeared possible all three could be approved, but we know that case is now highly unlikely. For now, there is only one still standing, however wobbly.
Arena was sent packing early when the FDA identified higher incidences of cancer in Lorcasarin preclinical studies. What many had thought was the best bet for safety was turned completely upside down. Vivus too, was dismissed- this time due to concern over cardiovascular and birth defect risks. In a surprise to obsesrvers, Orexigen's Contrave won majority backing of the FDA advisory panel, only to be rejected by the FDA, asking for a new trial seeking cardiovascular safety data; this will add many years and hundreds of millions of dollars to the drug's development.
There are analysts who have written off all three drugs; the FDA is in safety mode and wants to preempt the possibility of future recalls. Mathew Harper of Forbes has opined that the entire obesity drug field is essentially dead as a result of the Contrave rejection. He is wrong.
Both Lorcasarin and Contrave were only marginally effective in clinical trials of weight loss. They passed the FDA requirements for only one measure of efficacy; this made it easy for the FDA to make a negative decision based on the poor benefit to risk ratio. Even though Lorcasarin had two full years of data on thousands of patients, its true activity would never be known until use became widespread. The FDA simply was not willing to take any risks on a drug with such modest benefits.
Vivus' Qnexa stands out with a highly effective drug tested at three different doses. Results surpassed all FDA benchmarks for efficacy for the high and mid-doses. Even at the lowest dose, one benchmark was passed, making it as effective as either of the other two drugs.
Obviously, there is room for concern: FDA analysts pointed out that a higher percentage of patients in the studies discontinued the drug due to anxiety, sleep, and depression-related adverse events. Adverse effects on memory, attention, and language was noted along with concerns regarding increased heart rates. This may sound like a scary list, but these are known side-effects of topiramate and phentermine- the components of Qnexa.
What may have Vivus over a barrel is topiramate's teratogenic effects. A study of 178 babies born to women taking topiramate showed 16 had cleft lip or genital defects- an eleven-fold higher incidence. Thirteen babies born to women in taking Qnexa in the clinical trial had no signs of birth defects, but the sample size is very small. Vivus is now gathering additional data on topiramate and its affect on birth defects to present to the FDA.
The worry is that Qnexa will be used long term in women of child-bearing age, leading to a serious risk of increased birth defects. Vivus will certainly need to design a Risk Evaluation and Mitigation Strategy (REMS) satisfatory to the FDA. Keep in mind that even with its inherent risks, topiramate is approved and used by women as a preventative for migraines, a serious disorder, but surely less so than seizures.
Qnexa is not a weight-loss cure-all, but a drug that can shave 10% off the weight of a seriously obese individual is of real benefit.