Archive for February, 2012

The Calorie-Out Math is All Wrong

February 23rd, 2012

Two scientists from the National Institutes of Health (NIH) have presented a new mathematical model to calculate reductions in caloric intake needed to lose weight. The old formula of a reduction of 500 calories/day resulting in a pound a week weight loss is wrong, according the researchers. The reason for the error is that, as weight is lost, metabolism slows down. Therefore, ever greater intake reductions are needed. This is why so many dieters feel like failures. Bottom line: It’s not their fault. The researchers presented at AAAS in Vancouver.  Battling obesity with better mathematical models They have an on-line tool (which is not that easy to use)   http://bwsimulator.niddk.nih.gov/favicon.ico  . Their work was published in Lancet. Quantification of the effect of energy imbalance on bodyweight : The Lancet.

FDA Panel OKs Qnexa

February 23rd, 2012

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.

Qnexa’s Second At-Bat

February 17th, 2012

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.

Media interest is reflected in a front page story by Andrew Pollack in the New York Times. Diet Treatment, Already in Use, to Get F.D.A. Review – NYTimes.com

Son of Fen Implicated in French Deaths

February 11th, 2012

A French study has determined that a fenfluramine-deritative drug, half of the Fen-Phen combination, may be responsible for   3,100  hospitalizations and   1,300 deaths. Estimate of deaths due to valvular insufficiency attributable to the use of benfluorex in France – Fournier – 2012 – Pharmacoepidemiology and Drug Safety – Wiley Online Library  The authors  believe these figures are likely underestimations.

FDA Sets Hearing on Cardiovascular Aspects of Obesity Drugs

February 9th, 2012

The Food and Drug Administration (FDA) has announced two days of hearings on the role of cardiovascular assessment in the preapproval and postapproval settings for drugs and biologics developed for the treatment of obesity, March 28 and 29th, 2012 Advisory Committee Calendar > March 28-29, 2012: Endocrinologic and Metabolic Drugs Advisory Committee Meeting Announcement

Michelle Obama Changing Military Food Choices

February 9th, 2012

Reuters has reported that Michelle Obama will join in an announcement of new nutrition standards for the armed forces 1,100 dining facilities. Over a quarter of eligible 17-24 year olds are too overweight to join the military. Once in, members of the military are gaining too much weight. Department of Defense officials describe this as a “national security problem.” The military spends about $4.65 billion on food services each year and an estimated $1.1 billion on medical care associated with excess weight and obesity. http://www.reuters.com/article/idUSL2E8D90AO20120209

The military’s struggle with obesity has always been an interesting one. It is probably the largest sub-group in the US population with a high number of young people and a culture most supportive of physical activity. In addition, exceeding the different services’ weight standards can result in loss of a career. So, with all that, one would think it would have it’s weight problem pretty well under control. Yet, it isn’t which is probably due to the fact that it is not as isolated from the rest of society. In addition, the physical work of soldiers and sailors have given way to more and more technologically based skills.  Nonetheless, fighting wars, repeated deployments and family issues drives up stress. Obesity rates of US soldiers has doubled since the start of the Iraq war. Families are also affected. Tens of thousands of spouses have had bariatric surgery costing $363 million over ten years. Military spent $363million on WEIGHT-LOSS surgery for obese soldiers’ wives over last ten years | Mail Online One spouse reported becoming depressed and engaging in emotional eating and finally losing 118 pounds.

The future problems for military recruitment are very serious. John Cawley and JC Maclean have calculated that from 1959-2008 the percentage of the population ineligible for service more than doubled for men and tripled for women. They estimate that a 1% rise in weight and body fat would further reduce eligibility by over 850,000 men and 1.3 million women. Unfit for service: the implications of rising ob… [Health Econ. 2011] – PubMed – NCBI

Orexigen and FDA Agree on New Study

February 6th, 2012

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

How Blame Gets in the Way

February 5th, 2012

Recommended reading. Sara Sklaroff has written an eloquent essay on what it means to live with type 2 diabetes. On Our Own: Why We Who Struggle To Live With Diabetes Could Use A Helping Hand