Eisai Voluntarily Withdraws Belviq (Lorcaserin) from U.S. Market at FDA's Request Due to Cancer Risk

News Event

Today, the FDA issued a drug safety communication requiring Eisai to voluntarily withdraw its weight-loss drugs Belviq and Belviq XR (both with the generic name lorcaserin) from the market. The FDA’s analysis of the CAMELLIA-TIMI 61 cardiovascular safety clinical trial, which involved 12,000 participants, revealed that while Belviq did not increase cardiovascular risk, it was associated with an elevated risk of cancer. On average, one additional cancer case may occur for every 470 patients taking the medication for one year. The primary cancers observed included pancreatic cancer, colorectal cancer, and lung cancer. Eisai’s stock declined slightly by 1% today.

Drug Source Analysis

Belviq was originally developed by the US biotechnology company Arena and approved for weight loss in 2012. Due to the high demands of market promotion, Arena chose Eisai as its sales partner. However, the drug demonstrated only modest efficacy and even poorer sales performance. In 2017, Arena sold this once-promising potential blockbuster drug to Eisai for $23 million. Belviq is the only novel small-molecule weight-loss drug launched in the United States over the past two decades; the other two, Qsymia and Contrave, are combinations of existing drugs, alongside an injectable GLP-1 agonist. Another new molecular entity small-molecule weight-loss drug was Sanofi’s CB1 receptor antagonist Acomplia (generic name: rimonabant), which was marketed only in Europe and later withdrawn due to central nervous system side effects. Acomplia had been held in high esteem, with expectations extending beyond weight loss to potential applications in other central nervous system disorders. Its withdrawal dealt a significant blow to Sanofi. Last year, Sanofi announced its exit from the cardiovascular and diabetes therapeutic areas.

Belviq is a 5-HT2C receptor agonist with lower activity at the notorious counterpart, the 5-HT2B receptor. Agonist activity at the 5-HT2B receptor is considered the mechanism by which the former blockbuster weight-loss drug combination Phen-Fen, developed by Wyeth, caused valvular heart disease in patients. Wyeth paid billions of dollars in settlements yet still has not resolved all litigation. Last year, the French pharmaceutical company Servier was also taken to court for the aggressive promotion of Mediator, a drug in the same class, underscoring the difficulties and risks associated with the development and marketing of weight-loss medications. Eisai and Arena are likely to face substantial litigation in the future, despite the product having generated minimal revenue.

Following the Avandia incident in 2008, the FDA mandated cardiovascular safety trials for all diabetes and weight-loss medications to demonstrate their safety profile. This requirement not only significantly increased development costs but also led to unintended consequences, as seen with Belviq: while it showed no cardiovascular risk, it was associated with an increased risk of cancer. Admittedly, this regulation also spurred the development of glucose-lowering agents such as GLP-1 receptor agonists and SGLT2 inhibitors, which have been shown to reduce cardiovascular events. If Belviq indeed poses a cancer risk, patients should be informed immediately, especially given that carcinogenic risks were also observed in animal studies. However, the reliability of the difference in incidence rates (7.7% vs. 7.1%) remains questionable. Furthermore, the occurrence of tumors was not concentrated in any specific type, making the findings even more difficult to interpret. In obesity treatment, apart from weight reduction, there are few other restrictions; therefore, it is not surprising that patients with multiple comorbidities may experience imbalances in certain disease conditions.

All risks must be balanced against benefits. If you claim the risk is low, what magnitude of benefit can you deliver? This may well be the most pressing issue with current weight-loss medications. At present, only Qsymia and GLP-1 receptor agonists achieve more than a 10% greater reduction in body weight compared with placebo, and both are associated with side effects of varying severity. Belviq yields only a 5% greater weight loss than placebo—a marginal effect that hardly qualifies as impressive; given its suspected carcinogenicity, the FDA’s withdrawal of the drug required no second thoughts. Although obesity is a root cause of many chronic diseases, societal understanding of its harms remains inadequate, with many people viewing it merely as an aesthetic concern, which in turn lowers patients’ tolerance for the risks of anti-obesity medications. Energy conservation is one of the most fundamental safeguards for human survival, and disrupting this complex system is exceedingly difficult.