On 16 September, an FDA Advisory Committee had voted to recommend against approval of the drug based on concerns over both safety and efficacy.
Over the last ten years innovative drugs for the treatment of obesity have not had much luck with FDA approvals because of the risk of severe or serious adverse events and side effects. Meridia, another obesity drug, developed by Abbott, was taken off the market recently.
According to Arena Pharmaceuticals, the FDA's Complete Response Letter requested the following regarding non-clinical issues:
(That Arena) provide a detailed accounting of all slides prepared from female rats that contributed to mammary tumor incidence data in each update to the FDA and to the final study report; in consultation with the FDA, identify an independent pathologist or group of pathologists to re-adjudicate all mammary and lung tissues (neoplastic and nonneoplastic lesions) from all female rats; demonstrate that the apparent increase in aggressiveness of adenocarcinoma in rats administered lorcaserin is reasonably irrelevant to human risk assessment; and provide additional data/information regarding the distribution of lorcaserin to the CNS in animals and human subjects that would clarify or provide a better estimate of astrocytoma exposure margins.
Regarding lorcaserin's efficacy in obese and overweight individuals without type 2 diabetes, the FDA describe it as "marginal" and advised Arena to submit the final study report of the BLOOM-DM (Behavioral modification and Lorcaserin for Overweight and Obesity Management in Diabetes Mellitus) trial. The trial compared 12-month treatment with either lorcaserin or a placebo in overweight/obese individuals with type 2 diabetes. Arena hopes to announce trial results soon, and have a study report finalized by the end of 2010.
Jack Lief, Arena's President and Chief Executive Officer, said:
This is an important step for us toward the FDA's approval of lorcaserin. While the complete response letter provides us with recommendations from the agency, we intend to meet with the FDA to obtain further clarity on the approval path and timeline. We will work with the agency to address the issues with our NDA as quickly as possible.
A Type A meeting with the FDA will be requested, Arena informs, in order to clarify what the FDA needs. If granted, the meeting should take place within the next month.
Lonnel Coats, President and Chief Executive Officer of Eisai Inc., said:
Eisai is committed to collaborating with Arena to address the FDA's requests. Obesity is an epidemic in America, and our goal is to bring lorcaserin to physicians and patients who need additional weight loss options.
Lorcaserin is thought to act as a selective serotonin 2C agonist. The serotonin 2C receptor is expressed in the brain and is thought to be a key factor in regulating metabolism and appetite. Its serotonergic properties act as an appetite suppressant (anorectic). Arena is hoping to eventually market lorcaserin under the trade name Lorqess.
Sources: FDA, Arena Pharmaceuticals Inc.