The National Women’s Health Network is a nonprofit advocacy organization that works to improve the health of all women. We bring the voices of women consumers to the policy and regulatory decision-making bodies. We are supported by our members and do not take financial contributions from drug companies, medical device manufacturers, insurance companies, or anyone else with a financial stake in women’s health decision-making.

Obesity is associated with serious and life-threatening diseases and conditions, such as diabetes, hypertension, and heart disease. As prevalence of these conditions has grown, so has concern – as it should – but weight loss in and of itself doesn’t necessarily improve a person’s health. The Network believes that a woman taking a weight loss drug should have the FDA's assurance that the evidence shows the drug has been proven to make health better, not simply reduce the number on the scale. But the research Orexigen has done on this drug combination can’t support that claim. In fact, patients with serious or active cardiovascular disease -- one of the health problems that people seeking to lose weight most commonly are hoping to address – weren't even eligible for the trial because NB (naltrexone/bupropion) is contraindicated for them. And people with diabetes -- another serious health condition that might drive a weight loss effort -- were less likely than others to lose weight.

Even when measuring by weight loss alone, all four of Orexigen’s studies failed to meet one of the FDA’s effectiveness standards and only two of their three studies actually designed to assess efficacy met the other effectiveness standard. It’s worth noting that fourth study didn’t meet either standard because the comparison group was so successful at losing weight. People in this trial received intensive lifestyle modification, which resulted in those not taking a diet drug losing almost as much weight as those taking diet drugs in the other studies.

The sponsor has made only a weak case for weight loss effectiveness and has provided even less data about the effect on health outcomes. Moreover, there is no data on weight loss maintenance, which we know is especially difficult to achieve. Each of these studies lasted only one year – far too short a time to provide meaningful information on whether people will be able to maintain the weight loss.

If NB had no safety problems then weak efficacy might not be of as much concern, but this is not the case. In fact, one of the health conditions people are trying to alleviate by losing weight is made worse by NB – the increased risk of hypertension.

Another significant safety concern is the failure to thoroughly investigate the well documented risk of suicidality and neuropsychiatric side effects of bupropion, one half of this drug cocktail. Despite the established risks, Orexigen did not use the gold standard of suicidality assessment, which would have collected data on suicidal thoughts and other psychiatric side effects throughout of the studies. Instead, the sponsor used a retrospective assessment. Although this assessment did not find an increased risk, we urge the FDA not to approve a new indication for bupropion without first receiving data examining the frequency and severity of known risks in this new use. This is particularly important because previous studies have shown that these events have occurred in people with no pre-existing psychiatric problems, making it impossible to simply rely on the warning label to screen out those who might experience a problem.

The Network recognizes that people wanting to lose weight are looking for more options. However, consumers depend on the FDA to ensure that their drugs are safe and effective. Orexigen has failed to meet this standard – the effectiveness for weight loss is weak, the effectiveness for health outcomes is inadequate, and there are important safety concerns the company failed to thoroughly investigate – the risks outweigh the benefits. We recommend that the Committee vote against approval.

Kate Ryan is the NWHN Program Coordinator.