Arena Obesity Drug Helps Patients Shed a Few Pounds, Lower Risk of Heart Disease

San Diego-based Arena Pharmaceuticals disappointed a lot of investors a couple months ago when its obesity drug didn’t help people shed as many pounds as hoped. But after combing through the data in greater detail, the company says it has evidence that its drug can help many patients lose weight, and that it leads to all sorts of other health benefits, like potentially lowering the risk of cardiovascular disease.

Arena is presenting detailed results today from a clinical trial of 3,200 patients, known as Bloom, which compared its lorcaserin treatment to a placebo. The data being released today show that patients on the Arena drug for a year generally had lower blood pressure, lower cholesterol scores, improved blood sugar levels, and 30 percent lower levels of C-reactive protein in the blood—a marker for inflammation associated with higher risk of heart attacks.

The findings, which are being presented today at the American Diabetes Association annual meeting in New Orleans, could cause some investors to take another look at the prospects for lorcaserin, which was branded as a failure by many when the first hints of data were made public in March. The major finding of the study is 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. The FDA generally considers that a weight loss drug should be five percentage points better than a placebo—so on that score, Arena came up short.

Arena acknowledges that, but it’s trying to draw attention to a second FDA definition that gives the company reason for optimism that it will win approval for lorcaserin. If a drug helps twice as many patients lose 5 percent or 10 percent of their body weight compared to a placebo, that’s another valid definition for success, the FDA has said. On that count, Arena was a winner. About two-thirds of patients who stayed on the 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 triple the rate among those on a placebo.

“This has an opportunity to be the drug of first choice,” says Arena CEO Jack Lief. “Our ability to tie all of these outcome measures together, with a well-tolerated drug, is something no one else has.”

Any drug that can help people lose significant amounts of weight with no serious side effects has a chance to be a big seller. Obesity rates in the U.S. have been skyrocketing for years, with about two-thirds of U.S. adults now considered overweight or obese, putting them at risk for a litany of other conditions like heart disease, diabetes, high blood pressure, and arthritis. The cost to society of all this unhealthy weight gain is hard to measure because it’s intertwined with so many diseases, but a U.S. Surgeon General’s report in 2000 indicates that obesity may be responsible for about 9 percent of national healthcare spending.

Arena has two primary competitors in the race to develop an effective new drug for this epidemic. One is San Diego-based Orexigen Therapeutics , which combines a couple of generic drugs, naltrexone and bupropion, into a long-lasting formulation it hopes to market as Contrave. The other is from Mountain View, CA-based Vivus , developer of Qnexa.

None of those drugs has shown evidence that it can yet “make a dent” in the nation’s obesity problem, says Xavier Pi-Sunyer, the director of obesity research at St. Luke’s-Roosevelt Hospital in New York, a professor of medicine at Columbia University, and an investigator on the clinical trials of all three major obesity drugs in late development from Orexigen, Arena, and Vivus.

A hit drug in this disease would need to help people shed between 10 percent and 15 percent more of their body weight than a placebo, particularly because consumers will have to pay for these drugs out of their own pockets instead of getting insurance to pay, Pi-Sunyer says. Drugs like this will probably cost $150 a month, which will force many patients to really ask whether it’s worth the expense.

“I’m not sure any of the three drugs will make a dent in the problem,” Pi-Sunyer says. “When people have to pay for this out of their own pocket, they want something truly effective.”

Arena’s Lief was more optimistic. The dropout rate was similar for patients on the Arena drug and those who got a placebo. Depression rates were similar for patients on drug and placebo, and there was no increased tendency toward suicidal thinking, which was a rare side effect that ultimately prevented Sanofi-Aventis from winning U.S. approval of an obesity drug a couple years ago.

Importantly, Arena passed a rigorous test that looked at whether its drug might damage heart valves. That has been a concern since the start with this drug, because it is designed to curb appetite by hitting a similar receptor on brain cells that was blocked by Wyeth’s fen-phen drug combination in the 1990s. Fen-phen was pulled off the market because it also damaged heart valves. Arena’s drug was designed to have the same appetite-suppressing effect of fen-phen, without damaging heart valves.

Nonetheless, Wall Street reacted negatively, driving Arena stock down by 28 percent, from $4.50 to $3.23 on March 30, the day it announced that it wasn’t able to produce a 5 percentage point advantage over a placebo in average weight loss. Since then, the stock has recovered some, but not fully, climbing back to $3.92 heading into today’s medical meeting.

“Most investors have not gotten it yet,” Lief says. Many investors don’t appreciate how well-tolerated the Arena drug is, with a dropout rate similar to placebo, which is “unheard of” in the field of obesity drugs. There was also a high degree of variability in how individuals responded to the drug. About one-third of patients lost more than 5 percent of their body weight inside of two months. “Losing 5 percent of your body weight in less than two months is truly a big deal,” Lief says. “Most people don’t like to be on a diet for three to six months.”

A big check from a Big Pharma company that wants a partnership stake would go a long way for Arena in its quest to prove the doubters wrong. The company is having active talks, although Lief says he wouldn’t bet on a deal getting done until after results come out in September from another clinical trial, called Blossom. “If I were a partner, I’d want to see that last bit of data before we file (the application) to the FDA,” he says.

Source : www.xconomy.com

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