FDA Sets Cautious Tone For Prescribing Newly Approved Obesity Drugs

Agency offers perspective in New England Journal of Medicine that lays out the case for careful use of drugs in a space with medical need but a long history of products with toxic side effects.

FDA took to the pages of the New England Journal of Medicine Oct. 8 to emphasize to physicians that the recently approved obesity drugs Belviq (lorcaserin) from Arena Pharmaceuticals Inc. and Qsymia (topiramate/phentermine) from Vivus Inc. are not for people seeking “to lose a few pounds for cosmetic purposes.”

“It is important that their use be limited to patients for whom they are indicated,” FDA officials insisted. The perspective piece was authored by the Division of Metabolic and Endocrinologic Products Deputy Director Eric Colman, DMEP medical officers Julie Golden and Mary Roberts, DMEP Deputy Director of Safety Amy Egan, Office of Surveillance and Epidemiology Division of Risk Management safety reviewer Joyce Weaver and Office of Drug Evaluation II Director Curtis Rosebraugh.

FDA has been cautious in its review of the latest obesity drugs to come before the agency and urged prescribers to similarly take caution now that the drugs are reaching the market. Belviq and Qsymia both went through two review cycles while potential safety issues were examined – Belviq because of uncertainty about its relationship to valvulopathy and breast cancer, and Qsymia because topiramate is a teratogen. Orexigen Therapeutics Inc. must conduct a cardiovascular outcomes trial for Contrave (naltrexone/bupropion) before resubmitting the drug’s NDA to the agency (Also see "Orexigen On Quicker-Than-Expected Pace To Obtain Data Needed To Re-File NDA For Contrave" - Pink Sheet, 7 Aug, 2012.).

The agency is trying to set the tone for physicians as the two drugs begin their commercial lives and before loose prescribing practices can take hold. Vivus launched Qsymia Sept. 28, following July 17 approval (Also see "Vivus Qsymia Launch Includes Strategy To Overcome Medicare Hurdles" - Pink Sheet, 13 Aug, 2012.). Belviq is awaiting a Drug Enforcement Agency decision on controlled substance scheduling before it can enter the market (Also see "Belviq Gains FDA Approval For Weight Loss, But DEA Review Will Delay Launch" - Pink Sheet, 27 Jun, 2012.).

Medical Need Versus Safety

FDA’s caution and rationale for prescribing restraint rest on the tension between safety and medical need in the space. Obesity has reached epidemic proportions and can undermine patient health, Colman and his co-authors acknowledged. “The adverse health consequences of obesity are manifold, potentially involving all major organ systems and contributing to reduced quality of life.”

On the other hand, they listed a string of past failures that left the obesity field littered with products undone by safety issues. “Numerous once-promising weight-loss drugs have been abandoned because of serious toxic effects,” the article states.

In this category, they said, are aminorex, which caused pulmonary hypertension, fenfluramine and dexfenfluramine (valvulopathy), phenylpropanolamine (stroke), rimonabant (suicidal ideation and behavior) and most recently, sibutramine (myocardial infarction and stroke). Orlistat, marketed over-the-counter as alli by GlaxoSmithKline PLCand as prescription Xenical by Roche, remains the lone prescription drug approved for long-term treatment of obesity following Abbott Laboratories Inc.’s decision to pull sibutramine (Meridia) from the market in 2010 after the Sibutramine Cardiovascular Outcomes Trial found a slightly higher rate of cardiovascular events compared to placebo and failed to show an offsetting benefit (Also see "REMS Cannot Save Abbott's Obesity Drug Meridia In Face Of Cardiovascular Issues" - Pink Sheet, 8 Oct, 2010.).

“It was with this troubled history and the undeniable need for effective, safe weight-loss drugs in mind” that FDA reached the decision to approve Belviq and Qsymia, the agency officials said.

Both drugs are indicated as an adjunct to diet and exercise for weight management in obese patients with an initial body mass index greater than 30 kg/m² and in those with a BMI of 27 kg/m² with at least one weight-related co-morbid condition.

Unknown risks may lurk in the future for the two medicines, the FDAers warn, underscoring the importance of selecting patients who are appropriate to continue on the medications long-term.

Belviq labeling directs that patients who do not lose at least 5% of their baseline body weight by 12 weeks are to discontinue treatment. In the case of Qsymia, if patients do not lose 3% of their body weight by 12 weeks on a dose of 7.5 mg/46 mg, they are to discontinue the drug or increase the dose to 15 mg/92 mg. If patients do not lose at least 5% of baseline weight during an additional 12 weeks, they are to stop therapy.

FDA approved the drugs based on available data, the officials said, because in “some obese and overweight patients,” the drugs have favorable benefit-risk profiles for chronic weight management.

[Editor’s note: The October issue of Pharmaceutical Approvals Monthly features an analysis of FDA’s review of Arena’s Belviq. For more information, contact customer care at [email protected] or 800.332.2181 or visit www.elsevierbi.com/pharmaceutical-approvals to sign up for a free trial.]