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Obesity, defined as a body mass index (BMI) of 30 or greater, is a major risk factor for cardiovascular disease, certain types of cancer, type 2 diabetes, sleep apnea and respiratory disease, osteoarthritis and stroke.

According to the CDC, in 2009, only Colorado and the District of Columbia had a prevalence of obesity less than 20%.  In contrast, thirty-three states had a prevalence equal to or greater than 25%; nine of these states (Alabama, Arkansas, Kentucky, Louisiana, Mississippi, Missouri, Oklahoma, Tennessee, and West Virginia) had a prevalence of obesity equal to or greater than 30%.

This puts a huge burden on the healthcare system since obesity leads to many major diseases. Diet and exercise and over the counter diet pills have not worked significantly over the long-term Surgical procedures such as Roux-en-y gastric bypass surgery have been performed but like any surgical procedure comes with risk. This gastric bypass surgery is expensive and many insurance companies will not pay for the procedure although this is slowly changing.

Four companies have tried to develop drugs for obesity but as of this date, they have not been approved by the FDA or have been withdrawn from the market:

1. The first obesity drug was approved in 2007 - Meridia (sibutramine) by Abbott. At the request of FDA, Abbott voluntarily withdrew the drug starting in November of 2009 based on a "results of the six-year SCOUT study, which involved roughly 10,000 patients and was requested by European regulatory authorities as a post-marketing commitment to evaluate cardiovascular safety in high-risk patients. The majority of these patients had underlying cardiovascular disease and was not eligible to receive sibutramine under the current labeling. The European Medicines Agency suspended marketing authorization for all obesity medicines containing sibutramine in January 2010.

2. When Arena Pharmaceuticals submitted their weight drug lorcaserin for approval, the FDA issued a Complete Response Letter addressing their concerns about "signs of tumors found during an animal study and voiced concerns that the weight-loss experienced by non-diabetics in its clinical trials was marginal. Regulators asked for new data from a one-year study of obese and diabetic patients and asked Arena to come up with one or more independent experts to take a second look at the tumor data to see if the agency's cancer worries can be addressed." This is a major set back for Arena and one analyst thinks it may take up to 3 years before all the data is sorted out.

3. Vivus also received a Complete Response Letter from the FDA for their drug Qnexa. The FDA requested "a detailed plan to handle the risks Qnexa may present to women who are pregnant or may become pregnant. The agency also want data proving that elevated heart rate associated with the drug doesn't lead to cardiovascular problems. Vivus will have to provide results from an already completed 52-week study of the drug, an extension study for a subset of 675 patients who completed the CONQUER study. FDA requested continued discussion of Vivus' already-submitted REMS plan. Finally, the agency asked for safety update of any new adverse. Like lorcaserin, Qnexa will be a Schedule IV drug due to the phentermine component."

4. The final company to submit an obesity drug was Orexigen with Contrave. However, in February of 2011, the FDA had rejected its application and demanded a pre-approval cardiovascular study before it rules on an approval. Regulators told Orexigen that the trials would have to be of "sufficient size and duration to demonstrate that the risk of major adverse cardiovascular events in overweight and obese subjects treated with naltrexone/bupropion does not adversely affect the drug's benefit-risk profile."

With 4 companies initially rejected for their weight loss drugs, Matthew Herper from Forbes said "The field of obesity drugs is effectively dead," He also added that the FDA's requirement for additional trials would take years and cost a fortune, and will discourage any other company from pursuing an obesity drug program. "The clear lesson is that weight-loss medicines simply do not have enough of a benefit to justify any risk--and that this makes getting them approved just about impossible."

Closing Thoughts

The FDA is taking a strong position regarding the safety of these obesity drugs and making it difficult for pharma companies due to their evaluation of risk versus the benefits from these drugs. Serious cardiovascular risk particularly in a short period of time is far more serious than weight loss that may help to reduce the development of cardiovascular disease such as hypertension or diabetes that takes years to develop naturally.

However, if the FDA is requiring clinical trials that require a substantial number of patients and duration to satisfy their benefit-risk profile and making it literally impossible for any company to undertake, they will discourage obesity drug programs and basic research in this area.

At the present time, obesity drug development is fraught with too much risk.

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