Arena Reloads for Round 2 with FDA, With More Data on Weight Loss Drug in Diabetes Patients

11/9/10Follow @xconomy

Arena Pharmaceuticals is getting ready to make another run for U.S. regulatory approval of its obesity drug, and now it has some clinical trial data that the FDA has said it wants to see.

The San Diego-based biotech company (NASDAQ: ARNA) is announcing today that its experimental weight loss treatment, lorcaserin (Lorqess), reached all three of its main goals in a clinical trial called Bloom-DM, which enrolled 604 overweight or obese patients who also have Type 2 diabetes. The study essentially showed that these patients, who are generally tougher to treat than other overweight and obese patients, had a similar experience to more than 7,000 patients who participated in the last two pivotal trials, Bloom and Blossom. Some details are being released today to investors, while more details are expected to come out later at a medical meeting and peer-reviewed scientific journal.

Today’s data release represents Arena’s hope for redemption after what has been a brutal couple of months. The company’s application to market its treatment was ripped by FDA staff in September over some concern about tumors in rats, and then the agency formally turned down Arena’s application to start selling lorcaserin, saying it offered only “marginal” ability to help people lose weight. The FDA, in its complete response letter to the company, recommended that the company turn in detailed reports on this other study, Bloom-DM, to provide more evidence that the drug helps people who face the doubly whammy of obesity and diabetes. An estimated two-thirds of people in the U.S. are considered overweight or obese, which puts them at risk for a slew of other chronic, and costly, ailments like cardiovascular disease, arthritis, and depression.

So while the potential benefit—and market—for an effective weight loss would be huge, the FDA has also made clear through its actions this fall against both Arena and one of its competitors, Mountain View, CA-based Vivus (NASDAQ: VVUS), that any new drug developer must clear an extremely high bar for safety and effectiveness if it wants to start selling a new product to millions of people in need. San Diego-based Orexigen Therapeutics (NASDAQ: OREX), the next obesity drug developer in line at the FDA, will either learn from these lessons and advance onto the market, or step into yet another buzz saw when it appears before an FDA advisory panel on December 7.

Arena CEO Jack Lief wasn’t making any predictions about whether the Bloom-DM study will put his company over the top, but he expressed his usual confidence, and how this latest study will help buttress his argument that lorcaserin deserves a spot in the U.S. market.

Jack Lief

Jack Lief

“Patients with type 2 diabetes have much more difficulty losing weight than other patients. And although we believed they would benefit, you have to demonstrate that. This study has demonstrated they benefit as well,” Lief says.

Arena plans to crunch the numbers on this latest study, and discuss the new evidence with the FDA before the end of the year, Lief says. Arena’s partner, Japan-based Eisai Pharmaceuticals, remains committed to pushing forward with the program, a spokesman said.

OK, for the stat nerds out there who want to want to dig into what we’ve learned here, now you can get your hands dirty.

Patients who entered this study had an average body mass index of 36, Lief says. People with a body mass index of 30 or greater—which translates to 5-foot-10 and 209 pounds—are considered obese, according to the National Heart, Lung, and Blood Institute. They also entered the study with an average score of 8.0 on their hemoglobin A1c counts—an important measurement of blood sugar control. People are generally considered normal at an A1c score of 7.0, according to the American Diabetes Association guidelines.

Nothing really surprising stands out about the new set of data on weight loss for lorcaserin patients. A little more than one-third (37.5 percent) of patients on a twice-daily dose of the treatment lost at least 5 percent of their body weight after a year, which was more than double the rate of people who did that well on placebo (16.1 percent), Arena said.

While that satisfies one of the FDA’s standards for effectiveness in a weight loss drug, Arena once again showed that not every individual responds so well to the treatment. The median person in the trial lost 10.3 pounds (4.5 percent of body weight) after a year, compared with 3.5 pounds (1.5 percent of body weight) for those who got a placebo. The FDA has said it likes to see a new weight loss drug beat placebo by at least 5 percentage points on median weight loss, and lorcaserin in this case, only showed it was about 3 percentage points better—a consistent finding with the earlier studies of 7,000 patients.

As Lief points out, the FDA has said in its written guidelines that an obesity drug only needs to clear one of the two thresholds, but then again, the FDA did say lorcaserin offered “marginal” benefit on effectiveness. And today’s Bloom-DM result doesn’t appear on the surface to change the picture very much.

Still, Lief found reason for optimism in what the drug appeared to do for the symptoms of diabetes. Patients on lorcaserin had, on average, a 0.9 percentage point reduction in their hemoglobin A1c scores, which brought the average score down to 7.1—right on the edge of normal according to the American Diabetes Association’s guidelines. Half of the patients on the Arena treatment were able to reach the ADA blood sugar control goals.

“That’s a big deal,” Lief says.

About 8.6 percent of patients on the Arena drug dropped out because of side effects, compared with 4.3 percent of those on placebo. The most common adverse events were low blood sugar (hypoglycemia), headache, upper respiratory infections, and back pain. None of the reports of hypoglycemia were considered severe, Arena said.

One last thing in today’s statement has to make Arena followers pause, though. The Arena drug, which is designed to block a receptor in the brain that controls feelings of fullness, has always been closely monitored for safety because of the similarity of this target to a related receptor found on heart valves. Scientists say that the old fen-phen combination from the ’90s was sunk because it failed to distinguish specifically enough between these two receptors, which created a multi-billion legal liability when patients on the drug reported cases of damaged heart valves.

Arena, based on pooled data from 7,000 patients in its previous studies, showed a 2.3 percent rate of patients with heart valve damage (known as valvulopathy) on its drug, compared with 2.2 percent for those on placebo. The Bloom-DM study showed at the 24-week analysis point that 2.5 percent of lorcaserin patients had new cases of valvulopathy, while 1.9 percent on placebo had the condition. At the full-year follow-up point 2.9 percent of lorcaserin patients had new cases of valvulopathy, compared with 0.5 percent on placebo.

Lief dismissed the significance of this finding, saying the Bloom-DM study was so small that it wasn’t designed to detect any differences in valvulopathy that might be statistically significant. Since the overall number of patients in the study was small, one case of valvulopathy equals 0.5 percentage points, meaning that one or two cases can create the appearance of a difference that may not actually be real.

Even so, the FDA has shown that safety is paramount with any new drug that has potential to be taken by millions of people. History has shown that unpredictable things can start happening then, and when they do, the FDA gets raked over the coals by indignant Congressmen in televised hearings. The safer thing to do, for regulators, is to keep asking for more trials, more proof. It will be fascinating to see if Arena and its partner have the money, the guile, and the willpower to beat the odds and win the blessing of a very cautious FDA.

Arena plans to discuss the results and take questions from investors on a conference call at 8:30 am Eastern/5:30 am Pacific time today.

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