After a 12 year wait two weight loss drugs come along at once. Following Belviq (Arena's lorcaserin) in June, Qsymia (Vivus/topiramate/phentermine) became the second obesity drug to get approved in the space of a month.
Among approved weight loss agents, Qsymia is clearly the most efficacious; the highest approved dose has shown nearly 10% placebo-adjusted weight loss in Phase III trials. By comparison lorcaserin (Belviq) has demonstrated around 3% placebo-adjusted weight loss. Assuming there is not a huge disparity in price between emerging therapies efficacy will be the single most important factor in determining the competition dynamics of the emerging obesity market. Without reimbursement, patients will be required to foot the bill for weight loss treatments. Refilling prescriptions for a chronic use medicine can be huge burden on patient finances, and unsurprisingly the drug attribute thought to be most important in determining a patient's willingness to pay for a weight loss therapy is weight loss.
Qsymia is a combination of two centrally acting agents with appetite suppressant effects that are available as generics. One major threat to the success of Qsymia is that in the more cost-sensitive environments the generic components will be prescribed in place of the Qsymia brand. Both of Qsymia's components have been used widely for a long time but have known risks associated with their use. The topiramate label includes warnings that metabolic acidosis, cognitive dysfunction, suicidal ideation, depression, and mood problems may occur. Phentermine is approved for weight loss for short term use only; warnings associated with phentermine include the risk of blood pressure elevation and a range of cognitive side effects. A small elevation in heart rate was a concern raised at the FDA Advisory Committee meeting in February 2012. To demonstrate safety Qsymia will enter into a post marketing cardiovascular outcome trial that Vivus expect to begin in 2012. In total 10 post marketing trials will be required of Qsymia including trials in pediatric populations.
Topiramate exposure during pregnancy is associated with a fetal toxicity risk that has been a major point of debate in the Qsymia approval process. Qsymia is contraindicated in pregnant women (as are all weight loss therapies) and Qsymia prescribing information advises physicians to obtain monthly negative pregnancy tests in women of reproductive potential. A further prescribing restriction that has been applied to both lorcaserin and Qsymia states that if patients fail to achieve 5% weight loss after 12 weeks (at the highest dose) then treatment should be discontinued. The FDA is doing its best to strike a balance between sending a message to physicians and consumers that Qsymia is no miracle pill, without preventing access to the patients who need it most. Label warnings will constrain Qsymia sales but are by no means a disaster for Vivus and restrictions could have been harsher.
Vivus now has the challenge of launching a drug without the backing of a major pharmaceutical company but has the chance to beat rival therapy lorcaserin to market while lorcaserin seeks a scheduling designation from the DEA. It will be interesting to see how Qsymia is greeted by European regulators at a presentation to the CHMP scheduled for September 2012. Will the EMA follow the FDA to approve new weight loss therapies and what types of restrictions will be implementable across the different EU member states?