Thank you for the opportunity to testify on behalf of the National Research Center for Women & Families and our Cancer Prevention and Treatment Fund. I am Dr. Sonia Nagda, a physician trained in Public Health at Harvard. Our Center is dedicated to improving the health of adults and children, and we do that by scrutinizing scientific research. We do not accept contributions from companies that make medical products, so I have no conflicts of interest.
The major question facing you today is the same one you faced in 2010: has this drug been proven safe and effective, and if not, what studies are needed to determine if the FDA should approve it in the future?
The results for Lorcaserin indicate that a third to a half of the patients drop out because of adverse reactions or lack of benefit. Even those that stay on the drug benefit very little: the sponsor did not meet the categorical benchmark of a statistically significant 5% or more greater weight loss for the drug compared to placebo.
The placebo group – which had behavior modification only – were quite successful, and the combination of behavior modification and medication in the Lorcaserin group is certainly more effective than the medication would be without the behavior modification. So, what matters is not just subtracting the placebo statistics from the Lorcaserin statistics, but also keeping the benefit of the combination in mind.
Safety issues were raised in 2010 and must be raised again today. In 2010, this committee voted 9-5 against the FDA approval of lorcaserin. Based on the new data, this drug still does not merit approval. Additional research might change that conclusion, but it should be pre-market research, definitely not post-market research.
In contrast to the modest benefits of lorcaserin compared to behavior modification alone, there are substantial health risks. Most frightening was the increase in valvular heart disease, which is the condition that Fen-phen caused and why it was removed from the market. It is certainly possible that more people stopped taking the drug early because of adverse reactions than would be the case in the real world, causing biased results.
In their second year on the drug, two-thirds who had lost 5% of their weight kept it off for a second year compared to only half the patients who were switched from drug to placebo. That’s disappointing given how few patients lost 5% of their weight and stayed in the study.
In the BLOOM-DM trial:
- The risk of valvular heart disease was higher in patients taking lorcaserin than in those on placebo – a high enough risk that FDA would not dismiss it.
- There was valvular regurgitation, which could contribute to later heart disease.
- There was an increased risk of depression and suicidal thoughts.
- Although weight loss usually reduces blood pressure, lorcaserin increased hypertension,
- Lorcaserin patients were twice as likely to have heart attacks, strokes, or death.
The drug also increased:
- Abnormal dreams
- Suicidal thoughts
Hallucinations, memory impairment, disturbance in attention, amnesia, and other cognitive problems were also more likely with patients taking the drug, compared to placebo. These are all debilitating symptoms.
Lorcaserin increased the risk of breast cancer in rats, which seems to be the result of an increase in prolactin levels. It’s hard to know how to interpret those animal findings, but more research is clearly needed.
In summary, despite how difficult it is for people to lose weight, these studies show that behavior modification is effective and Lorcaserin does not improve that effectiveness for most patients.
A weight-loss drug does not need to work for all patients. If the company could determine which patients are more likely to lose weight and keep it off, and determine the health risks of the drug for that subgroup of patient, FDA might want to consider approval with a very carefully worded label and tough restrictions to prevent off-label use.
Until the subgroup most likely to benefit is clearly identified and the risks are determined to be less than the benefits, we ask you to urge the FDA not to approve this drug. It would NOT be ethical to approve the drug and do the studies afterwards because millions of patients could be harmed in the meantime.