Arena Obesity Drug Fails to Win FDA Approval, May Need More Clinical Testing

10/25/10Follow @xconomy

Arena Pharmaceuticals (NASDAQ: ARNA) sent out some devastating news around midnight Pacific time on Friday. The San Diego-based biotech company, after about a dozen years of effort and $1 billion of investment, said the FDA had turned down its application to market a new drug to help people in the U.S. lose weight.

Arena cited a complete response letter from the FDA, which said it could not approve the current application for the drug, lorcaserin (Lorqess) partly because it had “marginal” effectiveness in clinical trials, and because studies in rats showed that extreme high doses of the drug were linked to higher rates of cancer. If Arena is unable to prove the rat studies are irrelevant to human use, it may have to run more clinical trials to lay that concern to rest, the company said in the statement.

The application’s rejection is a painful setback for Arena, although it’s no surprise. FDA staff raised the concerns about rat tumors in public briefing documents last month, and an expert panel of advisors said in a 9-5 vote that the new weight loss drug shouldn’t be cleared for sale in the U.S. Still, Arena and its partner, Japan-based Eisai Pharmaceuticals, said they plan to meet with regulators to talk about next steps to see if they can resolve the stumbling blocks in their application. A huge amount is riding on this drug for Arena—it has no other drugs on the market, and nothing else close to reaching the U.S. market.

“While the complete response letter provides us with recommendations from the agency, we intend to meet with the FDA to obtain further clarity on the approval path and timeline,” said Jack Lief, Arena’s CEO, in a statement. “We will work with the agency to address the issues with our new drug application as quickly as possible.”

Anyone daring to develop obesity drugs in the past decade has been signing up for a perilous journey. Wyeth (now Pfizer) had to set aside $22 billion for legal settlements related to the fen-phen obesity drug debacle of the 1990s, after patients on the drug suffered damaged heart valves. Sanofi-Aventis stumbled a few years ago when a few cases of suicidal thinking derailed one of its weight loss candidates, rimonabant (Acomplia). And Abbott Laboratories voluntarily withdrew sibutramine (Meridia) at the request of the FDA earlier this month after a clinical trial raised concerns about cardiovascular risk.

This ought to be foreboding news for a couple other companies pinning their future on obesity drugs—San Diego-based Orexigen Therapeutics (NASDAQ: OREX) and Mountain View, CA-based Vivus (NASDAQ: VVUS). They are all vying for one of the biggest potential pharmaceutical markets ever. An estimated two-thirds of people in the U.S. are overweight or obese, although it’s unclear how many would opt to buy a new drug.

The Arena drug candidate has already been subjected to extraordinary safety scrutiny, because of its potential to treat millions of people with a chronic condition and because of the way it works in the brain. Patients were followed for two years to see whether the Arena drug caused any damage to the heart. The aggressive monitoring was required by the FDA because Arena’s drug is designed to work in a similar way as Wyeth’s fen-phen combination did in the 1990s. Arena’s candidate was designed to be more specific—to interact with an enzyme in the brain that controls feelings of fullness, without hitting the enzyme in the heart that derailed fen-phen.

Arena’s application was built on a pair of clinical trials that enrolled more than 7,000 people. The major finding of one of those studies, called Bloom, was that patients lost an average of 5.8 percent of their body weight on the drug, compared with 2.2 percent body weight loss in the placebo group. A second trial, Blossom, showed a similar result.

The FDA generally considers that a weight loss drug should be five percentage points better than a placebo—meaning that Arena wasn’t effective enough on that count. But the FDA has said there’s another way an obesity drug can be considered effective, if twice as many patients lose 5 or 10 percent of their body weight on a new drug, compared to a placebo. About two-thirds of patients who stayed in the Bloom trial a full year lost 5 percent of their body weight, compared with one-third who did as well on a placebo. More than one-third of the patients on the drug lost 10 percent of their body weight, which was almost three times the rate among those on a placebo. So that was the data Arena used to argue its drug was effective enough to deserve a spot on the market.

Many investors had already written off Arena’s chances of winning FDA approval based on the negative feedback of the advisory panel in September. So it will be interesting to see if and how Arena thinks it can rebound from this setback with the FDA. Arena plans to hold a webcast conference call with investors at 8:30 am Eastern time/5:30 am Pacific today to provide an update.

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