Orexigen Data on Contrave Cannot be Trusted, Top FDA Official SaysMar 9, 2015
A top U.S. Food and Drug Administration official says data showing that Orexigen’s obesity drug Contrave reduces the risk of heart attacks and cardiovascular death cannot be relied upon. Forbes reports that John Jenkins, director of the office of New Drugs, called the results "unreliable", "misleading" and "likely false". These findings caused shares of the company to jump up by 30 percent. In fact, if Orexigen does not rectify the situation it could face fines and civil penalties; Contrave could even be taken off the market.
Jenkins played a crucial role in the heart safety study of Contrave, Forbes reports. These trials are conducted to show that the drug does not increase cardiovascular events; the early data is supposed to be kept to a small, firewalled group of employees. "We required this study because we’re concerned that Contrave may cause adverse cardiovascular events because of its effect on blood pressure and heart rate. So the likelihood that that drug is going to have an early benefit is highly unlikely. So people need to be very cautious about making medical decisions based on these data, and we’re very concerned that investigators and patients may be unwilling to be in a trial based on these data when they are likely false readings of the actual effect of the drug." said Jenkins, according to Forbes.
Despite the fact that the findings reached a low p value (a statistical significance measure), Jenkins said "I think those are highly unreliable findings,"
"I am not a statistician, but I can tell you that Dr. Fleming, who is a statistician, and the statisticians at the agency, and other people who are expert in this area will tell you the only thing you can really conclude with confidence from this trial is that excess cardiovascular risk is not two or greater. You have a 95% confidence that the excess risk is not two or greater. You also have 95% confidence that the actual point estimate of the effect of this drug [on cardiovascular events] is somewhere below two. So the finding of .59 at the interim is highly unreliable independent of the p value." he said
Orexigen did not keep the data fire walled when it came to Contrave; FDA documents showed that over 100 people had access to the results. When the drug was approved, the FDA said a second study was needed. But now there are questions about whether this can be done due to data shown in a press release.
The agency noted two main problems with the Contrave heart trial. For one, the FDA said the data had leaked to too many people and that this could have changed the final result. Jenkins also said that far too many patients (over two-thirds) dropped off the study drug. However, the drop-outs stemmed from an FDA requirement in the trial; since the safety of Contrave was unknown, patients who were not losing weight were to be taken off treatment (or placebo). "The main reason we no longer have confidence in this trial to be the definitive answer to this question is the unblinding," says Jenkins.
Jenkins' main point is to not trust data Orexigen released about Contrave. "It points out the paradox of people rushing to believe the interim point estimate, because going into this trial all the priors were about cardiovascular harm. That shows the paradox of believing the interim analysis suggesting benefit."