On February 22, 2012, the Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC), a panel of experts who helps advise members of the U.S. Food and Drug Administration (FDA) regarding certain issues of the drug approval process, re-evaluated the safety and effectiveness of Qnexa, a drug manufactured by Vivus, Inc. to treat obesity.
The weight loss drug Qnexa is a combination of two agents previously approved by the FDA. The first ingredient in Qnexa is phentermine, an agent marketed as the appetite suppressant Adipex-P®. The second ingredient in Qnexa is topiramate, which is marketed as the anticonvulsant drug Topamax®.
Qnexa was originally evaluated by the EMDAC on July 15, 2010, after Vivus, Inc. submitted a New Drug Application (NDA) on December 28, 2009. For this NDA to receive FDA approval, Vivus, Inc. was required to show that Qnexa met specific criteria. First, because Qnexa contains two FDA-approved active ingredients (phentermine and topiramate), Vivus, Inc. was required to show that combining these ingredients did not cause them to become less effective or have negative side effects.
To complete this part of the study, mid- and high-doses of Qnexa were compared to mid- and high doses of phentermine, mid- and high-doses of topiramate and an inactive agent. At both mid- and high-doses, Qnexa caused approximately 3 percent more weight loss than either of its single components after 28 weeks. Consequently, the fixed-dose combination of drugs was acceptable to be used in Qnexa.
In addition, according to the 2007 Guidance for Weight Loss Efficacy, the FDA requires that a drug considered for weight loss purposes cause at least five percent higher average weight loss than an inactive (placebo) agent or it must cause at least 35 percent of treated people to lose at least five percent of their initial body weight (and this must be significantly greater than weight loss caused by an inactive agent).
According to initial studies conducted by Vivus, Inc., Qnexa caused 44.9 percent of treated people to lose at least five percent of their initial body weight after 56 weeks when given at a low dose. When given at a high dose, this percentage climbed to 66.7 percent. Only 17.3 percent of people receiving inactive treatment lost at least five percent of their initial body weight. This difference between people who received Qnexa versus inactive agents was statistically significant, thus the new drug met this second FDA criteria.
Despite its effectiveness at promoting weight loss, safety concerns regarding the effects of Qnexa on psychiatric, memory, heart-related conditions, as well as its likelihood for causing birth defects, was still unclear. In the initial safety studies conducted by Vivus, 20.6 percent of people receiving high-dose Qnexa showed negative psychiatric events, including sleep disorders, anxiety and depression. This value was twice as high as that observed for people receiving inactive agents. In addition, people taking high doses of Qnexa were four times more likely to experience a cognitive disorder, including attention difficulties, memory loss and reduced language skills, compared to people taking an inactive agent. Also, people taking high doses of Qnexa were two times more likely to experience irregular heart rhythms as compared to people taking an inactive agent, and their heart rate was approximately 1.6 times faster. Finally, when given at high doses to women who became pregnant, Qnexa was associated with deformation of the face and skull of the fetus.
Due to these safety concerns, the initial EMDAC members voted against approving Qnexa to treat obesity. The panel felt that more studies regarding the risk of increased heart disorders and birth defects was necessary.
Consequently, before the second EMDAC evaluation of Qnexa, Vivus, Inc. conducted an additional study evaluating the safety and effectiveness of this drug, with particular attention paid to analyzing the possibility that Qnexa may increase heart disorders or cause birth defects. Based on the new data, the EMDAC has reversed its initial decision and has voted 20-2 that Qnexa be granted FDA approval for treating obesity. Although the FDA is not required to follow the EMDAC recommendation, it will likely consider the panel's decision when it reviews the revised NDA submitted by Vivus, Inc. for Qnexa in October 2011.
Despite the success of Vivus, Inc. in gaining the EMDAC's approval for Qnexa prior to the FDA's evaluation of its NDA, very few drugs win FDA approval for treating obesity. However, many integrative therapies may be effective at improving weight loss. Listed below are examples of integrative therapies that have shown strong or good scientific evidence for improving weight loss or treating obesity.
5-HTP: good scientific evidence for treating obesity
Atkins diet: good scientific evidence for improving weight loss
Chitosan: good scientific evidence for treating obesity or improving weight loss
Conjugated linoleic acid: good scientific evidence for treating obesity or improving weight loss
DHEA: good scientific evidence for treating obesity
Ephedrea: strong scientific evidence for improving weight loss
Hydroxycitric acid: good scientific evidence for improving weight loss
Konjac glucomannan: good scientific evidence for treating obesity or improving weight loss
Korean pine: good scientific evidence for suppressing the appetite
Psychotherapy: good scientific evidence for improving weight loss
Salatrim: good scientific evidence for suppressing the appetite
When protein: good scientific evidence for improving weight loss or suppressing the appetite
For more information about integrative therapies for weight loss, please visit Natural Standard's Comparative Effectiveness database.
