FDA asks Eisai to withdraw weight-loss drug Belviq over cancer signal

The U.S. Food and Drug Administration asked Eisai Inc. on Feb. 13, 2020 to withdraw the weight-loss drugs Belviq and Belviq XR (lorcaserin) from the U.S. market after a long-term safety trial found more cancer diagnoses in patients taking the drug than in patients taking a placebo. Eisai agreed to voluntarily withdraw both products the same day ^[1][2].

The evidence came from CAMELLIA-TIMI 61, a randomized, double-blind, placebo-controlled trial of about 12,000 men and women who were overweight or obese. It ran from January 2014 to June 2018 at more than 400 sites in eight countries, including the United States ^[1][2]. Patients had established cardiovascular disease or were at high risk for it; men had to be at least 50 years old, and women at least 55 with type 2 diabetes plus one additional cardiovascular risk factor ^[1]. Median follow-up was 3 years and 3 months ^[1].

During the trial, 462 patients taking lorcaserin (7.7 percent) were diagnosed with cancer, compared with 423 patients taking placebo (7.1 percent) ^[1][2]. Those patients received 520 and 470 primary cancer diagnoses, respectively. Pancreatic, colorectal and lung cancers were among the types that occurred more often in the lorcaserin group. The FDA described the difference as one additional cancer per 470 patients treated for one year. There was no apparent difference in cancer incidence in the first months of treatment, but the imbalance grew with longer time on the drug ^[1].

The same trial found no meaningful difference between lorcaserin and placebo in major adverse cardiovascular events. The hazard ratio was 1.005, with a 95 percent confidence interval of 0.842 to 1.198, and the upper bound stayed below the noninferiority margin of 1.4 ^[1]. Eisai said the trial showed lorcaserin produced sustained weight loss without a higher rate of major cardiovascular events than placebo ^[2].

The FDA said the cancer findings outweighed the drug's benefits, that the imbalance persisted across multiple analysis approaches, and that a chance effect could not be ruled out. The agency said the finding could not be adequately addressed through labeling, and that investigating the signal further would require safety endpoints that are unlikely to be readily or ethically studied in a clinical trial. The FDA concluded the drug would not be considered safe and effective if reintroduced ^[3].

Eisai's view differed. "Eisai's interpretation of the data from the CAMELLIA-TIMI 61 trial differs from that of the FDA," the company said, adding that its assessment was that the products "continue to have a positive benefit-risk profile in the patient population for which they are indicated" ^[2]. Eisai also noted the drug had been studied in more than 30 clinical trials involving over 22,000 patients ^[2].

Why it matters for patients

Belviq was approved in June 2012 as an addition to a reduced-calorie diet and increased physical activity for chronic weight management in adults with a body mass index of 30 or higher, or 27 or higher with at least one weight-related condition such as hypertension, high cholesterol or type 2 diabetes ^[3]. Lorcaserin is not a GLP-1 medication, and the withdrawal documents do not address semaglutide, tirzepatide or orforglipron. They do not report a cancer signal for those drugs, and they do not report that GLP-1 medications were studied in this trial.

The case shows how a required post-approval trial can change a drug's regulatory status years after it reaches the market. CAMELLIA-TIMI 61 was required when lorcaserin was approved in 2012 to evaluate cardiovascular risk ^[1][3]. The cancer difference was small in absolute terms — 7.7 percent versus 7.1 percent over a median of about three years — and the agency said chance could not be ruled out, but the finding still ended the drug's U.S. marketing ^[1][3].

For people who took lorcaserin, the FDA said it is not recommending special screening, and that standard cancer screening recommendations should apply regardless of prior lorcaserin treatment ^[1]. The FDA told patients to stop taking the drug and to talk with a health care professional about alternative weight-loss medicines or weight management programs ^[1]. It also described how to dispose of unused pills: mix them with an unappealing substance such as dirt or used coffee grounds, seal the mixture in a container and put it in household trash, or bring them to a drug take-back location ^[1].

What happens next

The FDA published a notice on March 4, 2021 determining that Belviq and Belviq XR were withdrawn from sale for reasons of safety or effectiveness. As a result, the agency said it will not accept or approve abbreviated new drug applications for generic lorcaserin hydrochloride tablets of 10 milligrams or 20 milligrams ^[3].

The FDA said additional evidence would be necessary to investigate the cancer signal, and that preclinical or clinical studies would need to be conducted first to address the agency's concerns about cancer and reproductive safety ^[3]. Whether any such studies are planned has not been reported.