Some health experts are calling for federal drug regulators to place restrictions on the obesity drug Contrave, due to the actions of officials and researchers working on a clinical trial, who overstated the drug’s benefits before they could be proven.
In an editorial published in the Journal of the American Medical Association (JAMA), former FDA deputy director Joshua Sharfstein and researcher Bruce Psaty call for the FDA to restrict use of Orexigen’s relatively new drug, after the company prematurely claimed Contrave has heart benefits, even though only 25% of the clinical trial was completed.
The release of information revealed that Orexigen officials had been improperly given access to the trial data and the clinical trial was halted. However, the FDA had already approved the drug for market based on interim results. The incomplete results were published in the same issue of JAMA on March 8.
Researchers note in the published data that the heart safety of Contrave remains uncertain, and also found that 14.2% of users suffered gastrointestinal events that may have been caused by side effects of Contrave, compared with 1.9% among those taking a placebo. The findings also suggest that 5.1% of users developed central nervous system problems, compared to 1.2% who were given a placebo.
Contrave (naltrexone-bupropion) is a combination of drug abuse and smoking cessation drugs like Vivitrol and Zyban, and was developed and distributed by Orexigen in partnership with Takeda Pharmaceuticals. It was approved by the FDA in 2014, and already carries a black box warning for the risk of suicidal behavior and other neuropsychatric events known to plague bupropion.
Drs. Sharfstein and Psaty recommend that the FDA use its regulatory muscle to restrict Contrave, possibly through a Risk Evaluation and Mitigation Strategy (REM), to punish the company for releasing incomplete and misleading data, and to warn consumers and the medical community that the actual benefits of Contrave are unknown and it is unclear if the benefits outweigh the risks, which can include gastrointestinal illness and central nervous system problems, according to the partial study results.
The pair also raised questions about the FDA’s process of approving drugs with only interim cardiovascular trial data, pointing to the Contrave case. However, the FDA has argued that cardiovascular trial data can take years to develop, and that it would create long delays if drug manufacturers had to wait until they were completed to place a drug on the market.
The revelation of the partial trial data occurred when Orexigen CEO Mike Narachi filed for a patent for Contrave, using the partial data. The patent process made the data go public and gave the appearance that the drug had cardiovascular benefits which had never before been seen. Critics say Narachi should have never had access to the data, and the Cleveland Clinic, which had been employed to conduct the clinical trial, halted the research and canceled its deal with the company in protest.
A new clinical trial is being conducted, but the results may be years away. In the meantime, doctors have already written more than 765,000 Contrave prescriptions.