Arena Pharmaceuticals has had a miserable weekend as regulators in the USA have rejected its investigational obesity drug lorcaserin.
The US Food and Drug Administration has issued a complete response letter regarding lorcaserin, citing a number of reasons for its decision. The agency is particularly concerned about tumours found in animal studies and what it believes are limited benefits of the drug, which is partnered with Japan’s Eisai.
Specifically, the FDA wants much more information about a rat carcinogenicity study. Arena needs to hire independent pathologists “to re-adjudicate all mammary and lung tissues” from all female rats and has to demonstrate that “the apparent increase in aggressiveness of adenocarcinoma in rats administered lorcaserin is reasonably irrelevant to human risk assessment”. The company also has to provide additional data regarding the distribution of lorcaserin to the central nervous system in animals and human subjects that would clarify or provide a better estimate of astrocytoma exposure margins.
The agency said that the weight loss efficacy of lorcaserin “in overweight and obese individuals without type 2 diabetes is marginal” and recommended that Arena submit the final study report of the BLOOM-DM trial, which has just been completed. Worryingly for Arena and Eisai, the FDA also stated that “in the event evidence cannot be provided to alleviate concern regarding clinical relevance of the tumour findings in rats, additional clinical studies may be required to obtain a more robust assessment of lorcaserin’s benefit-risk profile”.
Furthermore, the regulator told Arena that if approved, it would recommend placement of lorcaserin in “Schedule IV of the Controlled Substance Act”, though the CRL “provided the opportunity to complete preclinical studies that may lead to a different recommendation”.
Jack Lief, Arena’s chief executive, said the company will meet with the FDA “to obtain further clarity on the approval path and timeline”. The rejection came as no surprise, seeing as how the agency’s Endocrinologic and Metabolic Drugs Advisory Committee voted 9 to 5 against approval just over a month ago.
No new weight loss drug has been approved by the FDA since Roche’s Xenical (orlistat) in 1999 and in July, the EMDAC voted 10-6 against backing Vivus’ Qnexa (phentermine/topiramate). Orexigen Therapeutics’ Contrave (sustained-release naltrexone/bupropion), partnered with Takeda, is scheduled to go in front of the panel on December 7 but analysts believe the agency, which earlier this month called on Abbott Laboratories to suspend sales of its controversial obesity drug Meridia (sibutramine) over cardiovascular safety fears, will keep the bar high for these types of treatments.
