Orexigen Therapeutics Inc.’s new diet pill, Contrave, has safety risks and unclear benefits, according to U.S. regulators deciding whether to approve the nation’s first new prescription drug for obesity in more than a decade.
Contrave was linked to more cases of high blood pressure, psychiatric side effects, dizziness and kidney dysfunction in studies reviewed in a Food and Drug Administration staff report released today. The drug met one of two recommended measures of effectiveness.
Orexigen and partner Takeda Pharmaceutical Co. are the last of three sets of companies seeking U.S. approval this year for new medicines to treat the estimated one-third of Americans who are obese. Safety concerns have doomed previous weight-loss drugs, including Abbott Laboratories’ Meridia, which was pulled off the market in October because of heart risks.
“They may have to do a thorough cardiovascular study before approval,” said Elemer Piros, an analyst at Rodman & Renshaw in New York, in a telephone interview today. “The clear precedent is Meridia. It’s so fresh in our minds that I don’t think the FDA wants to embark on a public experiment in an uncontrolled setting without this information.”
Outside advisers to the FDA are scheduled to review the Contrave findings Dec. 7 in Silver Spring, Maryland. A final decision on approval is due by Jan. 31. Competing products being developed by Arena Pharmaceuticals Inc. and Vivus Inc. were delayed by the FDA in October because of safety concerns.
Orexigen, based in La Jolla, California, fell 66 cents, or 12 percent, to $4.81 at 4 p.m. New York time in Nasdaq Stock Market composite trading, the biggest single-day percentage decline since May 4, 2009. The stock has fallen 35 percent so far this year. Arena, based in San Diego, gained 3 cents, or 2.2 percent, to $1.42. Vivus, of Mountain View, California, rose 15 cents, or 2.2 percent, to $6.87.
Piros downgraded Orexigen to “market underperform,” from “market perform,” with a target price of $2.
Contrave, Orexigen’s first product, is a combination of two approved drugs that target different parts of the brain that influence appetite and cravings. The pill contains bupropion, an antidepressant also used to quit smoking, and naltrexone, a treatment for alcohol and painkiller addiction.
The safety concerns raised by the FDA are consistent with what is known about the two components of Contrave, said Adam Cutler, an analyst at Canaccord Adams in New York. He said the advisory panel members are likely to vote that a cardiovascular outcomes trial can wait until the drug is on the market.
“If they get a chance to say they want more information but they’re okay getting that after it’s approved, it might make some people more comfortable,” Cutler said in a telephone interview today. “If we were to come out of this panel with a positive recommendation, I think you could see the stock up 200 percent or more.”
Cutler projects Contrave will be approved and bring in $1 billion in peak U.S. sales in 2016.
In terms of effectiveness, the proposed maintenance dose of the drug helped patients lose 4.2 percent more weight than a placebo pill after 56 weeks, short of the FDA recommended benefit of 5 percent, the agency said. The drug met an alternative benchmark that satisfies the FDA’s 2007 guidelines by helping at least 35 percent of patients, twice the proportion of those on placebo, lose at least 5 percent of their weight.
“It is difficult to draw accurate conclusions about the long-term efficacy” of the proposed maintenance dose of Contrave, said Eric Colman, deputy director of the FDA’s Division of Metabolism and Endocrinology Products, in a memo to the advisory panel included in the staff report.
Two-thirds of American adults are overweight, raising their risk of diabetes, heart disease, high blood pressure and cancer, according to the 2008 National Health and Nutrition Examination Survey. More than one-third of American adults are obese, measured as a ratio between height and weight.
“You just have to look around and see the state of the United States to realize this is a very big opportunity,” said Joshua Schimmer, a biotechnology analyst at Leerink Swann in Boston, in a telephone interview today. “It’s a big market.”
While the FDA has urged companies to research new diet pills, safety is critical for weight-loss products because they may be taken by millions of people for a long period of time.
The agency hasn’t approved a prescription weight-loss drug since Basel, Switzerland-based Roche Holding AG’s Xenical in 1999. Safety concerns led to the withdrawal of Wyeth’s fen-phen in 1997 and the rejection of Paris-based Sanofi-Aventis SA’s experimental rimonabant drug in 2007. Wyeth is now owned by New York-based Pfizer Inc.
Sales of prescription weight-loss drugs fell 11 percent last year to $153.7 million, according to IMS Health Inc., a research company in Norwalk, Connecticut. Of the almost 7.5 million prescriptions dispensed, four of every five were for generic phentermine, a short-term appetite suppressant.