Senate Committee Calls on FDA to Support Development of Obesity DrugsTuesday, September 13, 2011
Yesterday, at the 47th EASD meeting, I spent most of my time in sessions dealing with the improvement of insulin.
While there was a lot of fascinating basic and clinical science and, certainly, newer insulin analogues appear less obesogenic than their older cousins, this entire line of treatment at least for type 2 diabetes, by definition, cannot be considered anything other than palliative (even if diabetologists would argue that insulin treatment helps prevent many of the complications of diabetes).
Indeed, if we consider obesity as one of the main ‘modifiable’ risk factors for type 2 diabetes (some would prefer the term ‘root cause’), then treating diabetes without also treating obesity, is hardly a solution.
Unfortunately, our ability to treat obesity ranges from the notoriously limited “Eat-Less-Move-More” (ELMM) approaches to the rather drastic surgical treatments, with little in terms of conservative medical treatment in between.
This, as I have often discussed in the past, is in part due to the rather ultra-conservative approach that regulators have taken towards approving obesity drugs – a situation that has considerably stifled enthusiasm of pharmaceutical companies to forge ahead with the necessary investments in this area.
It is therefore perhaps occasion for guarded optimism to note that in a report accompanying the 2012 US appropriations bill for agriculture, rural development and FDA, the US Senate Committee on Appropriations has now directed the FDA to provide a report by March 30, 2012, regarding steps the agency will take to support the development of new treatments for obesity.
The committee was apparently “concerned with the absence of novel medicines to treat obesity” and called the lack of obesity drugs “a significant unmet medical need,” noting that obesity is “a disease linked to cancer, high blood pressure, heart disease, diabetes, and stroke” and is the second leading cause of preventable deaths in the US.
The committee’s directive for FDA to look at risk mitigation recognizes that safety issues have been a major stumbling block for developers of weight-loss drugs.
Such steps, the report says, include the use of Risk Evaluation and Mitigation Strategies and other post-market authorities “to mitigate risk and ensure rigorous post-market scrutiny while increasing access to novel medications.”
On a side note, the FY12 bill, as part of the Transforming Food Safety and Nutrition Initiative, states that
“the FDA will also begin an $8.8 million program to improve nutrition labeling on restaurant menus and vending machines so that consumers can adopt healthier diets….the investments in this initiative will empower consumers to make better nutritional choices and will motivate food producers to develop healthier foods.”
While I am not sure, what influence the infusion of a paltry $9 Million into food labelling and similar (‘educational’) approaches will have, I do believe that the strongly worded ‘warning’ to the FDA regarding taking a more ‘supportive’ attitude towards finding ways to hasten the development and launch of new anti-obesity drugs, may prove promising.
I know for one that despite a rather large number of molecules in early pipelines (and a few that are further along) as well as the substantial number of druggable targets, many large pharmaceutical companies appear to have taken a rather unenthusiastic ‘wait-and-see’ attitude towards developing competitive anti-obesity portfolios.
At least from what I see here at the EASD, there appears far greater enthusiasm for playing it safe, even if only with another ‘me-too’ launch in the already ‘overloaded’ anti-diabetes market.
The FDA will now need to report back in six-months – I (as many others) will be watching closely to see what they come up with.
From my perspective, risk mitigation strategies must include development programs and approval pathways that target ‘complicated obesity’ (Edmonton Obesity Stages 1-4) rather than simply weight loss, and take the rather heterogenous nature and etiological heterogeneity of obesity into account (there is absolutely no reason why any obesity drug should work for all – rendering average weight loss or even response rates meaningless).
It is perhaps time for companies and researchers to begin ‘pigeon holing’ obesity drug development into categories that better reflect risk and aetiology in a manner that would essentially make BMI-based definitions and approaches obsolete.
Tuesday, September 13, 2011
How frustrating it is not to have the intragastric balloon approved in the US! Do you see any hope for this simple, non-surgical solution? I know you have reservations because it isn’t a “permanent” intervention – I must admit, that’s why I prefer it.
Thursday, September 22, 2011
Thank-you, Dr. Sharma, for sharing your unusually clear-headed perspective on a complicated, life-threatening, and treatable disease.
Friday, February 17, 2012
This is an excellent article Dr. Sharma. As you know, there are two new obesity drugs before the FDA this year for consideration. Qnexa from Vivus, which is a proprietary combination of two generics (phentermine and topirimate) and a novel drug from Arena Pharma called lorcaserin. The FDA released their briefing documents for an Advisory Committee on Qnexa today that shows valid concern on being able to enforce a strong REMS for the drug since it is a combination of two currently available generics. Given the risks associated with the drug for birth defects, increased BP and cognitive AE’s; the FDA may be hesitant to approve it.
However, lorcaserin appears to be a very safe drug for the FDA to approve given the sponsor’s recent study results completed to respond to the CRL from the FDA. There is no risk of valvulopathy, at least a 24X margin of safety for any increased risk for cancer and the main AE is a mild and transient headache. Although the drugs placebo-adjusted weight loss is modest, the completer statistics are impressive with 3-4X more patients losing 10% of their body weight than placebo. Most importantly the drug approves all co-morbidity factors including reducing HbA1c in a diabetic population by an impressive .9%. This is the type of novel therapy the FDA should allow in the hands of physicians and monitor any concerns through post-marketing studies.