Following the same fate as other applicants this year, Vivus also received a complete response letter (CRL) regarding its NDA for obesity therapy, Qnexa. FDA’s CRL detailed clinical, labeling, REMS, safety-update, and drug-scheduling requirements.
Somewhat surprisingly, the company’s stock price was up 32% in early morning trading and continuing to rise. Investors are likely responding to the fact that FDA did not require further clinical studies and Vivus says that it already has data to prove that Qnexa does not increase cardiovascular risks, one of the agency’s concerns. “We are preparing a comprehensive response to the CRL for submission to the FDA in approximately six weeks,” says Leland Wilson, CEO of Vivus.
The firm’s NDA sought to market Qnexa for the treatment of obesity, including weight loss and maintenance of weight loss, in patients who are obese or overweight with co-morbidities such as hypertension, type 2 diabetes, dyslipidemia, or central adiposity.
Four days ago Arena and Eisai were also slammed with a CRL for their weight-management drug, lorcaserin. And earlier this month, FDA asked Abbott to remove Meridia from the market after a clinical trial pointed to cardiovascular risk. Orexigen’s obesity treatment, Contrave, will face review by FDA’s advisory committee in December. This is the same panel that voted against approval of Qnexa and lorcaserin.
Qnexa combines phentermine, an amphetamine-like appetite suppressant, and topiramate, a marketed antiseizure medication. It has been developed as an oral, controlled-released, once-a-day formulation. Qnexa is also in Phase II development for the treatment of type 2 diabetes and obstructive sleep apnea.
In the clinical section of the CRL, the FDA requested a comprehensive assessment of topiramate's and phentermine/topiramate's teratogenic potential. This will include a detailed plan and strategy to evaluate and mitigate the potential teratogenic risks in women of childbearing potential taking the drug for the treatment of obesity. FDA also asked Vivus to provide evidence that the elevation in heart rate associated with phentermine/topiramate does not increase the risk for major adverse cardiovascular events.
On REMS the FDA requested that a discussion of an already-submitted REMS plan be continued after the written response from Vivus has been submitted. The agency also asked for a safety update of any new adverse events.
FDA stated that if approved, phentermine/topiramate would be a Schedule IV drug due to the phentermine component.
The agency requested that the company formally submit the results from the already-completed Sequel study (OB-305), a 52-week extension trial for a subset of 675 patients who completed the previously reported 56-week Conquer study. In September the firm reported Sequel results showing that Qnexa allowed patients to lose an average of 11.4% of their initial body weight and improved various weight-related co-morbidities under study.
All patients in this trial had at least two weight-related co-morbidities and an average baseline BMI of 36.1. Vivus says that patients receiving the highest dose of Qnexa achieved and maintained an average weight loss of 26 pounds over the two years.