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 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 any other entity 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 – which has increased efforts to prevent these conditions by reducing obesity. But weight loss in and of itself doesn’t necessarily improve a person’s health. The Network recognizes that there is an unmet need in this area and that women and their health care providers want more options. At the same time, we believe that a woman taking a weight loss drug should have the FDA's assurance that the drug is safe, and that there should be evidence that it has been proven to improve health, not simply reduce the number on the scale. While some women may seek and be satisfied with weight loss alone, they still want that assurance that the drug will help them achieve and maintain that lower weight without compromising their health.

Unfortunately, Qnexa does not give women what they need. Although the drug appears to be effective in assisting weight loss during the first year of use, the evidence shows that people taking Qnexa gain weight in the second year; that health benefits from the weight loss are uncertain at best; and perhaps most importantly, the sponsor has not adequately answered the safety concerns about the drug that were raised by the Committee when it rejected Qnexa in 2010.

Before I go into more detail about the Network’s concerns with Qnexa’s safety and efficacy, I’d like to briefly address the serious methodological problems with the second-year data provided by the sponsor in this application. When Qnexa was rejected, Vivus could have responded by continuing its trial in a way that would have allowed it to gather robust, longer-term data to address the questions and concerns that had been raised about its drug. Instead, the sponsor continued the trial in a way that significantly undermines the value and meaning of the longer term data it is presenting today. Vivus narrowed the patient population in the trial such that only 25 percent of the first-year participants continued through the second year. The small number of sites selected to continue in the second year omitted the worst performing sites, which skewed the data in ways that make the results far less meaningful and reliable than what the FDA, National Women’s Health Network Statement on Qnexa, February 22, 2012 clinicians and the public – should be able to expect. As you consider Qnexa’s second application, please keep in mind the FDA’s warning that the second-year data are “best case scenario” results.

Vivus’ original studies do show Qnexa’s mid-dose treatment meets both of the FDA’s effectiveness standards after one year – but we urge the Committee to put those results in context and ask for more. Although people on the recommended dose did lose on average 8.5 percent of their weight after one year – while those not on the drug lost only 2 percent of their weight – Qnexa’s effectiveness did not continue in year two. As the FDA stated in the Clinical Briefing Document, “all treatment groups experienced weight gain in the second year” (emphasis added). Similarly, the evidence of health benefit from taking Qnexa, which was small to begin with, also seems to vanish in the second year. The data showed a slight decrease in blood pressure for those on the drug at the end of the first year, but this benefit was gone by the end of the second year. And after two years, there was no benefit for those with diabetes – a health problem that people seeking to lose weight are commonly hoping to address – compared to those not taking the drug. Keep in mind that these are the results from patients at the best performing sites.

Still, we recognize that temporary weight-loss without additional health benefits might be acceptable to some consumers if the drug was clearly safe, but that is not the case. The FDA previously rejected Qnexa because of serious safety concerns, in particular unanswered questions about cardiovascular and birth defect risks – and those questions remain unanswered. Although the sponsor could have conducted a trial to look specifically at cardiovascular risks before resubmitting its application, it did not. Instead, Vivus merely did new analyses of existing data, and those analyses have not resolved the serious safety concerns raised previously by this Committee about this drug.

To address the question of cardiovascular risk, the sponsor did a cardiovascular risk analysis report of its clinical trial data despite the fact that their original studies weren’t designed to assess cardiovascular risks and benefits. Vivus has also focused on the first year of data despite the fact that the FDA and Committee concerns were about increased heart rate over time. Moreover, as a women’s health advocate, we are particularly concerned that the measurement tools used by the sponsor have only been proven to work with men, leaving women without any meaningful information about the cardiac risk this drug might pose to them. To address the question of birth defects, the sponsor submitted studies of topiramate exposures during pregnancy. The results of these studies varied greatly, ranging from a sponsor-funded study that found no association between the drug and birth defects to an analysis showing a five-fold increased risk. Once again, the data provided fail to answer the important, outstanding safety questions.

In conclusion, 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. Vivus has failed to provide adequate evidence to demonstrate that Qnexa meets this standard – the effectiveness for health outcomes is inadequate, the effectiveness for weight loss maintenance is weak, and the sponsor did not provide answers to the safety concerns raised by the Committee and the agency in 2010 – the available evidence to date shows that the risks of Qnexa outweigh its benefits. We recommend that the Committee vote against approval – again.