

The Network recognizes that women and their health care providers want more options for dealing with the problem of obesity, which is associated with serious and life-threatening diseases and conditions, such as diabetes, hypertension, and heart disease. At the same time, we believe that the well-justified the concerns about obesity, the unmet need in this area of medicine should not lead to approval of drugs that are ineffective or unsafe – or worse, both. A woman taking a weight-loss drug should have the FDA's assurance that the drug is safe and that there is evidence that it will improve her health.

Unfortunately, the FDA cannot give women those assurances about lorcaserin. This drug barely met the efficacy benchmarks established by the FDA, and people taking it gained weight during the second year of use. Perhaps most importantly, the sponsor has not adequately answered the cardiovascular safety questions that the Committee raised when it rejected lorcaserin in 2010.

Of all the weight-loss drugs that have come before the FDA in recent years, lorcaserin is the least effective. All three of Arena’s studies failed to meet at least one of the FDA’s effectiveness standards and only two of the three met the other effectiveness standard. Furthermore, even the modest weight loss experienced by those taking lorcaserin in the first year did not continue in year two. As the FDA stated in the Clinical Briefing Document, “all treatment groups regained body weight from Week 52 to Week 104.” While those who continued on the drug regained less, the trend was clearly in the wrong direction and we have no information about what would happen beyond two years.  But none of these conclusions about effectiveness are new. The committee had all this information when it reviewed and rejected the lorcaserin application less than two years ago.

The additional clinical trial data submitted by the company this time came from its diabetes trial. Unfortunately, it doesn’t improve the picture. People with diabetes, who might be expected to be more highly motivated to lose weight, were actually less likely than others to achieve weight loss. And that’s saying something when you consider that lorcaserin was only minimally effective in the previous two studies, which the Committee noted in 2010 were limited to a relatively healthy group of people compared to the typical obese population.

While a small amount of weight loss might still be of value if the evidence showed that the drug were very safe, that is not the case for lorcaserin. Serious unanswered safety questions about the potential for lorcaserin to cause valvular heart disease, raised when lorcaserin was rejected in 2010, remain unanswered. The Committee rightly recognized then that it would be negligent to pass over these questions lightly, given the tragic experience with fen-phen, a weight-loss drug that had a similar mechanism of action to lorcaserin and was removed from the market because it caused VHD. In 2010, the agency stated that it could not rule out an excess risk of VHD based on the studies submitted and that is still the case today. Additionally, the current FDA Clinical Briefing Document notes that people taking lorcaserin experienced higher rates of individual valve regurgitation, an indicator of VHD.”

In conclusion, the available evidence to date shows that the possible risks of lorcaserin outweigh its possible benefits. While we recognize that people seeking to lose weight are looking for more options to assist them, there is too much uncertainty about the safety of lorcaserin and too little evidence that it can provide meaningful help to those patients. Consumers depend on the FDA to ensure that their drugs are safe and effective, and Arena has failed to provide adequate evidence to demonstrate that lorcaserin meets this standard. We recommend that the Committee vote against approval – again.