The US Food and Drug Administration (FDA) has declined to approve Arena Pharmaceuticals' New Drug Application (NDA) for lorcaserin, a weight loss drug that the company hopes to sell through a partnership with Eisai.
The FDA issued a Complete Response Letter (CRL) for the application stating that the NDA cannot currently be approved for both clinical and non-clinical reasons, including insufficient evidence of efficacy and safety concerns stemming from the development of tumours in rats who were administered the drug. The agency said that additional clinical studies may be required to establish the drug's benefit-risk profile.
Arena said it plans to meet with the FDA as soon as possible to clarify the agency's requests. Eisai, which has licensed exclusive marketing rights to the product in the US, said it remains committed to collaborating with Arena to meet the agency's requirements.
Lorcaserin is intended for weight management, including weight loss and maintenance of weight loss, in patients who are obese or overweight and have at least one weight-related co-morbid condition.
However, the FDA said in its letter that the weight loss efficacy of lorcaserin in overweight and obese individuals without type 2 diabetes was only marginal in the study results submitted in the NDA. The agency recommended that Arena submit the final study report of a trial called BLOOM-DM (Behavioral modification and Lorcaserin for Overweight and Obesity Management in Diabetes Mellitus), which evaluated lorcaserin versus placebo over a one-year treatment period in obese and overweight patients with type 2 diabetes.
Arena said it expects to have top-line results from that study within a few weeks and to have a completed study report by the end of the year.
The FDA also said that Arena would have to take a number of further steps to demonstrate the drug's safety, given the findings of tumours in rats, including hiring an independent pathologist approved by the agency to reevaluate tissues from the study rats.
The FDA said that, based on the studies currently submitted, the agency would recommend that the drug be made a Schedule IV product under the Controlled Substance Act, which would mean that there would be some restrictions on how often the prescription may be refilled. However, the CRL invites the company to complete and submit additional preclinical studies to change that determination.
This is not the first bad news for pharmaceutical treatments for obesity. At the beginning of the year the European Medicines Agency (EMA) recommended the suspension of the marketing authorisation for Abbott's sibutramine, and the company recently withdrew the drug from the US market.
The FDA is also due to make decisions on two other weight loss drugs in the coming months: Qnexa (phentermine/topiramte) from Vivus and Contrave (naltrexone/bupropion) from Orexigen. According to inThought analysts, Qnexa has a 69 per cent probability of gaining approval, and Orexigen is 70 per cent likely to be approved. However, in light of the rejection of lorcaserin, approvals for Qnexa (which has already received a negative recommendation from the advisory panel) and Contrave seem less likely.