New Obesity Drug?

Something which could cause a great deal of excitement is on the horizon in obesity treatment. Arena Pharmaceuticals, a San Diego biotech firm, has an anti-obesity drug in development. The drug, named Lorcaserin, activates specific brain serotonin receptors which suppress appetite, reduce food intake, and produce weight loss. This late-stage developmental drug is still several years away from possible FDA approval. Arena has it on the FDA approval track and has big event scheduled to occur in late March, 2009 when the company will first report results of a Phase 3 clinical trial. The company hasnt revealed any details of the 2-year Phase 3 trial as yet, but if the results are as impressive as those of the Lorcaserin Phase 2 trials, and if Phase 3 trials raise no safety issues then Lorcaserin may be the drug everyone has waiting for.

The two-drug combination of phentermine and fenfluramine or, Phen/Fen, activated these same serotonin receptors. For many patients Phen/Fen was a magical combination, which made food cravings, especially carbohydrate cravings, disappear and produced almost effortless weight loss. Unfortunately, a small number of patients developed cardiac valve leakage caused by the fenfluramine because fenfluramine activates all serotonin receptors including the 5-HT 2B receptors on cardiac valves. The fenfluramines were withdrawn from the market. Although the FDA was suspicious for a while that phentermine could have played a part in causing the heart valve problem, it is well documented now that phentermine has no adverse cardiovascular effects. Phentermine was exonerated and remains the most frequently prescribed anti-obesity drug.

Lorcaserin should be cardiac-safe because it activates one and only one specific serotonin receptor, the 5-HT 2C receptor but does not activate the cardiac 5-HT 2B receptor. Patients in the Phase 3 trial were monitored with echocardiograms and Arena will be announcing the analysis of that data along with the efficacy data in late March. The results of the 12-week Phase 2 trial were recently published in the medical journal Obesity (Smith SR, Prosser WA, Donahue DJ, Morgan ME, Anderson CM, Shanahan WR. Lorcaserin (APD356), a Selective 5-HT2C Agonist, Reduces Body Weight in Obese Men and Women. Obesity 2008;17:494-503.). Adverse effects were limited to headaches, nausea, and dizziness. Headaches usually started on day one, lasted a few hours and were mild. Nausea was also typically a drug start up effect and then disappeared. Dizziness occurred in about 7% of the patients in the trial. There were no significant cardiac or psychiatric adverse effects.

Weight loss appeared at 2 weeks and was progressive throughout the 12-week trial. The weight loss achieved at 12 weeks was comparable to the weight loss at 12 weeks of other weight loss drugs such as sibutramine. The non-responder rate was very low with nearly all patients losing weight in the Phase 2 trial. This is interesting because in the Phase 2 trial the patients were not put on diets and did not receive even advice on changing behaviors. In other words, nearly all the patients lost weight by merely taking the drug and doing nothing else. If the Phase 3 trial results in about 3,000 patients confirms and extends the Phase 2 trial results in about 400 patients, Lorcaserin could be the next blockbuster obesity drug. This preliminary Phase 2 report show results for 12 weeks only but a crucial question is what happens in the next 12 weeks of therapy and thereafter. This is why the Phase 3 trial results are eagerly awaited.

Even if it is eventually approved by the FDA, the earliest date Lorcaserin might be available at pharmacies will likely be 2012. The FDA has been very slow to act on new drug applications lately and the agency has always been extremely slow in approving new obesity drugs. Overweight patients shouldnt wait for a new drug before dealing with this illness.

It looks like Lorcaserin alone produces an average 3% weight loss at 12 weeks or about one third the weight loss our patients get on our Very Low Carbohydrate Diet program which includes a great deal of attention to behaviors and behavior modification without any weight loss drug. Our patients who have phentermine added, experience on average a 15% weight loss at 6 months. Although a 3% weight loss at the highest dosage at 12 weeks may seem low, one should remember this is in patients who arent even trying to lose weight they just took the drug. I would expect Lorcaserin will be like any other drug in that it will do much better combined with a comprehensive weight loss program. Will Lorcaserin be a better drug than phentermine? Well see. It will most certainly be much more expensive than phentermine.

I'll continue to watch for news on this exciting developmental drug and willpost new information here in this Blog as it becomes available. Check back often.