March 3rd, 2012
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March 14 is coming up and it is an important date. It is the deadline for written comments to the Food and Drug Administration for the March meeting of the Endocrinologic and Metabolic Drug Advisory Committees. The meeting is not to review any specific drug but rather the “role of cardiovascular assessment in the preapproval and postapproval settings for drugs and biologics developed for the treatment of obesity.” (For full information on filing written comments see, Advisory Committee Calendar > March 28-29, 2012: Endocrinologic and Metabolic Drugs Advisory Committee Meeting Announcement )
A member of the EDMAC made the comment at the last meeting that all obesity drugs were basically diabetes drugs and the same rules that apply to diabetes drugs, in terms of cardiovascular risk, should apply to obesity drugs. When Qnexa was approved, its high level of effectiveness tipped the scales in favor of a post-approval cardiovascular study, a la SCOUT. However, the FDA has not made a final decision. This meeting might prove decisive in whether long-term cardiovascular trials will be required pre-approval for obesity drugs.
One of the interesting aspects of this discussion will be the contrast between cardiovascular study design, which calls for an older, sicker population in order to have a sufficient number of events versus the clinical population usually seen in obesity practices. This was a major issue in the interpretation of the SCOUT trial and the EDMAC hearing on Meridia.
Sure to come up at the next Ad Com will be an evaluation of the cardiovascular risks in SCOUT which found that modest weight loss of approximately 3 kg appeared to offset the increased cardiovascular mortality of sibutramine for the following 5 years, even in those with pre-existing cardiovascular disease. Maintained intentional weight loss reduc… [Diabetes Obes Metab. 2011] – PubMed – NCBI
February 23rd, 2012
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Yesterday, the Endocrinologic and Metabolic Drugs Advisory Committee 
voted overwhelmingly, 20-2, in favor of approval of Vivus Inc.’s anti-obesity drug, Qnexa. It was one heck of a surprise.
The morning session included presentations by the company and the FDA staff on the effectiveness of Qnexa and, especially, the safety profile. The safety issues involved the issue of whether additional birth defects, particularly oral clefts, would result from wider administration of topiramate and whether phentermine contained a risk for cardiovascular events. The panel members were clearly wrestling with understanding the data. The company presented a very comprehensive Risk Evaluation and Management System (REMS) plan to reduce exposure to the drug by women of child-bearing potential. During the discussion, committee members and the FDA expressed concern that the REMS program might be too restrictive. They observed that if access were too limited, patients could do what they are doing now – use the two drugs in the generic forms off-label for obesity treatment.
Considering the cardiovascular risks, they were concerned about the relatively weak, but nevertheless present, sign of increased heart beats per minute and what that meant. This indicated a cardiovascular outcomes trial (like the SCOUT study for Meridia). The issue was whether the study would be done prior to approval or post approval. The key comments were made by Dr. Sanjay Kaul, usually a hawk on the obesity drugs, who opined that having the trial conducted post-approval would not be unreasonable. The effectiveness of the drug, about a 10% weight loss over a year, was the tipping point.
During the public witness part of the meeting, I testified, along with Ted Kyle for the Obesity Society, Denise Bruner for the American Society of Bariatric Physicians, Chris Gallagher for the American Society for Metabolic and Bariatric Surgery and Joe Naglowski for the Obesity Action Coalition. Ever since Qnexa was turned down in July 2010, we had been encouraging each other to testify and hold up the case for recognition of obesity as a disease and requiring additional tolls to fill the ‘treatment gap’ between lifestyle changes and bariatric surgery.
We huddled together as the votes were cast. The discussion among the panel members all day was of the ‘one the one hand on the other hand’ type. We expected a close vote. So, we nearly fell over at the 20-2 vote in favor of approval. Of course, the FDA has the final word and it does not have to follow the recommendations of the panel. Nevertheless, it seems more likely than not that the FDA will approve.
At the end of day, I felt that the long shadow that the phen-fen debacle has cast over the FDA might be lifting and that the panel may have achieved a higher recognition of the enormous implications of our ever growing obesity epidemic.
Arena Pharmaceuticals and Orexigen Therapeutics are still in the game with their drugs. While this positive vote, on the one hand may be good news for them, it may also set the effectiveness bar at a height their drugs cannot meet. Time will tell.
February 17th, 2012
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Interest is rising as Vivus Inc.’s next date with the Food and Drug Administration draws near. The Endorinologic and Metabolic Drug Advisory Committee meeting on February 22, 2012 will reconsider whether to approve Qnexa, which is a combination of phentermine and topiramate. Both drugs are already approved by the FDA and are available as generics. The FDA has put out their briefing materials, as well as that from Vivus on their website. Endocrinologic and Metabolic Drugs Advisory Committee > Briefing Information for the February 22, 2012 Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee
The materials indicate that the Advisory Committee will be debating how to mitigate the exposure by women of childbearing potential to half of the Qnexa compound, topiramate.
February 9th, 2012
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February 6th, 2012
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Orexigen Therapeutics Inc. has announced that it has reached agreement with the Food and Drug Administration on a new protocol to test for adverse cardiac events for it obesity-fighting compound, Contrave. Orexigen Therapeutics, Inc. – Press Release
February 2nd, 2012
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Most US middle and high schools sell soft drinks, candy and chips to their students. These practices have been widely criticized as contributing to childhood and adolescent obesity. However, a new study followed approximately 19,450 children from fifth to eight grade. Researchers found the children’s weight gain was not associated with the introduction or the duration of exposure to competitive foods. This did not vary by gender, race/ethnicity or family socioeconomic status. Possible explanations are that children’s food preferences and dietary patterns are firmly established before adolescence. Also, schools are highly structured whereas home life may have more opportunities for snacking. http://www.asanet.org/images/journals/docs/pdf/soe/Jan12SOEFeature.pdf.
February 2nd, 2012
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Accountable Care Organizations are predicted to replace health insurers in 20 years, according to 2 prominent health care policy makers, Ezekiel Emanuel and Jeffrey Liebman in the New York Times. The End of Health Insurance Companies – NYTimes.com.
The authors point to a shrinking market of traditional insurers and the changes coming under health care reform. Mainly, they look to the model that the ACOs will be paid a fixed rate per enrollee, not on a fee for service basis, with a bonus for meeting quality goals. They will have an incentive to keep their people healthy and out of hospitals.
What are the implications for obesity prevention and treatment? Frankly, we have seen this type of prediction before with the development of health maintenance organizations in the 1990s. The authors recognize this but predict that the information systems today will overcome the restrictive practices of HMOs. In theory, it would seem ACOs would want to encourage their enrollees to achieve as healthy weight as possible. On the other hand, perhaps they will find a way to avoid enrolling patients with obesity or limit services to them. We wait with bated breath.
January 26th, 2012
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The National Institutes of Health has come out for expanded A1c testing. Their press release and fact sheet point out that the A1c test does not require fasting and helps identify diabetes and pre-diabetes. They recommend testing of anyone 45 years old or younger than 45 are overweight, inactive or have at least one risk factor for type 2 diabetes. New NIH fact sheet explains test for diabetes, prediabetes, January 26, 2012 News Release – National Institutes of Health (NIH)
