EU Rejects Obesity Drug Qsiva for the Second Time

Lisa Nainggolan

February 26, 2013

The European Medicines Agency (EMA) has again refused to grant approval for the new obesity treatment phentermine/extended-release (ER) topiramate (Qsiva, Vivus) in the European Union.

The EMA's Committee for Medicinal Products for Human Use (CHMP) first rejected the product in October but was asked by the company to reexamine the decision.

Defending its second rebuttal, the CHMP said it "has concerns about the medicine’s long-term effects on the heart and blood vessels, particularly due to the effects of phentermine, which is known to increase the heart rate but whose long-term effects are not clear." Second, there are "concerns about the long-term psychiatric effects and cognitive effects related to the topiramate component of Qsiva," it noted.

The EMA noted that there was a high probability that, if approved, "the medicine would not be used strictly for the intended patients. The applicant did propose measures to reduce this risk, but the measures were considered difficult to implement in practice," so it concluded that "the benefits of Qsiva did not outweigh its risks."

Vivus says the European agency would also require a cardiovascular-outcomes trial to establish long-term safety before the product could be approved.

US Approved Product Under REMS Last July

Peter Y. Tam, president of Vivus, said in a statement that the company "is disappointed with the CHMP decision. We have worked diligently throughout Europe with key opinion leaders and regulatory and risk management experts to highlight the favorable safety and efficacy profile of Qsiva. Despite the positive recommendation of CHMP's own Scientific Advisory Group (SAG) and the high unmet medical need in obese patients, a majority of CHMP members have failed to recognize the importance of making this treatment option available, particularly for patients whose only effective intervention is surgery."

The EMA's decision runs counter to that of the US Food and Drug Administration (FDA), which approved phentermine/topiramate ER, which acts as an appetite suppressant, in July last year.

It is marketed as Qsymia in the United States under the risk evaluation and mitigation strategy (REMS), which includes guidance for safe prescription — the drug will be dispensed only through specially certified pharmacies — and use.

In addition to this safety measure, the manufacturer will conduct postmarketing studies, including the long-term CV outcomes trial suggested by the FDA's advisory panel in February 2012 to investigate the effect of phentermine/topiramate ER on risk for major adverse CV events, such as myocardial infarction and stroke.

It took 2 attempts to get Qsymia approved in the US: the product was rejected the first time it went in front of an FDA advisory panel in 2010, and the agency subsequently turned it down.