This week the DMEDP released its long-awaited revision of its 1996 clinical guidance for development of weight-loss drugs. Most of the changes were expected, based on a 2004 advisory committee hearing to discuss the topic. Highlights of the new guidance include delineation of the recommended exposure to active treatment (3,000 subjects for at least one year) in placebo-controlled studies and tips for getting claims of obesity-related complications into the label.
I hadn’t necessarily expected the FDA to provide specific guidance for making metabolic syndrome claims. They surprised on the side of logic and scientific evidence; good for them.
Here’s the relevant paragraph:
The term metabolic syndrome represents a cluster of laboratory and clinical findings that serve as markers for increased risk for cardiovascular disease and type 2 diabetes, and, depending upon the definition used, is prevalent in as much as 25 percent of the adult American population. The FDA does not necessarily consider the metabolic syndrome to represent a distinct disease entity. At present, there is no single etiological factor or central pathogenetic abnormality identified as mediating the constellation of excess visceral adiposity, abnormal lipids, elevated blood pressure, and insulin resistance that comprise the metabolic syndrome. Nonetheless, in addition to lifestyle modification, a host of drug therapies now exist to address individual or multiple components of the syndrome (e.g., lipid altering agents, antihypertensives, insulin sensitizers). Ideally, a therapeutic product intended to treat metabolic syndrome should normalize or improve all components of the syndrome, independent of weight loss (see section VIII), and ultimately be shown to prevent the development of type 2 diabetes and reduce cardiovascular morbidity and mortality.
As S-A investors will undoubtedly recall, S-A has emphasized for the last two years that Acomplia benefits patients with metabolic syndrome (see this, for instance). However, it looks like the FDA is demanding a demonstration that a drug improves each of the metabolic syndrome components and/or improves cardiovascular morbidity/mortality independent of weight loss before it will allow the use of the phrase “metabolic syndrome” in a drug’s indications for usage.
S-A made it clear that it was hoping to get an indication for metabolic syndrome, presumably because it believed that drugs targeting metabolic syndrome would be viewed more favorably by third-party payers than drugs targeting weight loss and secondarily improving obesity-related complications. But this type of thinking is highly speculative over mid-range timeframes, even if supported by quantitative market research, because the attitudes of third-party payers change over such timeframes in response to environmental factors, such as prevailing academic medical opinion, political pressure and public opinion.
Bottom line for now is that investors and drug developers should not expect to get a claim for metabolic syndrome until they are willing to spend the money needed to establish the validity of such a claim. For those seeking claims for obesity and its complications, the new FDA guidance provides a clear blueprint for approval in the U.S. Most of its teachings will also transfer directly to the EU and elsewhere.