Obesity: Three New Drug Candidates Promise A New Dawn

Obesity: Three New Drug Candidates Promise A New Dawn

Arena is positioning its pending anti-obesity NME lorcaserin as the cure for the obesity market hangover induced by the troublesome side effect profiles associated with earlier Rx weight loss products.

Cardiovascular concerns overwhelmed Wyeth/Solvay's Redux (dexfenfluramine) and Wyeth's Pondimin (fenfluramine) and are dogging Abbott's Meridia (sibutramine). Sanofi-Aventis' rimonabant was sunk by psychiatric adverse events.

Lorcaserin, submitted in December 2009, is the first of a new class of drug, the serotonin 2C receptor agonists. In pivotal trials, the NME did not increase the risk of cardiac valvulopathy, Arena CEO Jack Lief told the BIO CEO and Investor Conference Feb. 9. Arena also found no signal of depression or suicidal ideation, he assured the conference.

Arena hopes to outlicense lorcaserin, even though the obesity market has been a risky one for big pharma, and memories of the embarrassing market recalls by Wyeth and Sanofi-Aventis were reinvigorated by Abbott's Jan. 21 announcement that it was withdrawing sibutramine in Europe at the EMEA's urging due to a study finding increased risk of cardiovascular events ('The Pink Sheet' Jan. 25, 2010). FDA instead chose to strengthen Meridia labeling, but the findings re-energized Public Citizen's campaign to have the drug withdrawn in the U.S.

Arena has been touting the profit potential of lorcaserin for big pharma with presentations focusing on the importance of primary care physicians, who the company reports write 64 percent of anti-obesity prescriptions. The market is still dominated by phentermine (the "phen" in the notorious phen/fen combination), which holds 80 percent of anti-obesity total Rx market share, according to Arena; Lief predicted that lorcaserin could replace phentermine and other non-selective agents in patients requiring long-term therapy.

However, Arena will have to overcome mixed results in its Phase III trials. Lorcaserin only met one of two efficacy criteria FDA accepts for obesity drug approval, and only met it for one of two doses studied ('The Pink Sheet,' Sept. 28, 2009).

Less equivocal results have been posted by the two combination products in late-stage development (Pharmaceutical Approvals Monthly, October 2009). Like Arena, Vivus also submitted a December 2009 NDA for its candidate Qnexa, a combination of topiramate and phentermine. Both drugs could reach the market in 2010, if FDA accepts the datasets on the first review. Orexigen's Contrave (bupropion/naltrexone) is on track for a first half 2010 NDA filing.

- Bridget Silverman ([email protected])