Fen-phen was the wonder drug for weight loss in the 1990s, until it was found to damage heart valves and yanked off the market. Now the folks at San Diego-based Arena Pharmaceuticals are eagerly waiting clinical trial results that will show whether they have learned something profitable from that colossal failure.
Arena is developing a drug, lorcaserin, which it says should have the same appetite-suppressing ability of fen-phen, without the nasty side effect. Next month, Arena is expected to lift the veil on a pivotal study of 3,182 patients, which it hopes will show its drug can cause weight loss without any damage to heart valves after two years of follow-up.
This is a critical moment for Arena (NASDAQ: ARNA). The company, founded in 1997, has no products on the market yet and has run up an accumulated deficit of $656 million. The risks are huge: Madison, NJ-based Wyeth has coughed up a staggering $21.1 billion and counting in legal liability settlements to date from the fen-phen debacle. Of course, if Arena’s drug is safe and effective, the returns could also be enormous. About two-thirds of U.S. adults in the U.S. are overweight or obese, which makes them more likely to get a litany of other conditions like heart disease, diabetes, high blood pressure, and arthritis. The cost of all this excess poundage is hard to measure because it is so intertwined with other diseases, but a U.S. Surgeon General’s report pegged it at $117 billion in 2000, or about 9 percent of national health care spending.
So, naturally, any drug that helps people lose more than the FDA’s guideline of 5 percent of body weight, can be taken as a convenient oral pill, and have minimal side effects, is going to be big. The opportunity is probably worth $5 billion to $10 billion a year in sales, according to various analyst reports.
“Everybody here is very excited about it, this is a big event for us,” says Dominic Behan, Arena’s chief scientific officer.
Arena has been trying for years to assure investors that lorcaserin is safe for the heart. The Bloom study, which began in June 2006, has already passed a pair of interim analyses by independent safety monitors, who said it appeared safe after six months, and after a year of follow-up, Arena has said. The safety monitors were looking at high-resolution images taken by echocardiograms.
The study was designed to follow these patients for a full two years, and these results from the echocardiograms will be analyzed next month, Behan says. The company will also say whether the drug hit its all-important goal of producing at least a 5 percent loss of body weight for patients on the drug, compared with those on the placebo, after one year of follow-up, Behan says.
If this data turns out positive, a lot of dominos could fall into place. The company will seek to present full data in a prominent journal, or at a medical meeting. It will almost surely heat up negotiations with potential Big Pharma partners. And it will provide part of an application—along with a 7,000-patient trial called Blossom—that the company hopes to put together for the FDA by the end of this year.
Arena has gotten as far as it has because it has passed animal studies showing its drug can specifically stimulate a serotonin receptor in the brain called 5-HT2c, which is associated with sending signals to tell the body it’s full and to stop eating. There are 14 receptors in this family of serotonin receptor subtypes, which are structurally similar, Behan says.
One of those members of the family is 5-HT2b, a receptor found on heart valves that Arena most definitely wants its drug to avoid. “It’s very important to develop a drug that’s specific to the 2c receptor, and that can avoid other receptors,” Behan says.
The Bloom study will provide the most thorough evidence to date on whether lorcaserin works, but data from smaller trials so far have shown encouraging signs. A mid-stage study of 469 patients found that patients lost more weight on progressively higher doses. Patients on the highest dose, a 10 milligram, twice-daily pill, lost 7.9 pounds after 12 weeks, compared with 0.7 pounds for placebo patients. More than 90 percent of patients on the high dose had some degree of weight loss, and about one-third reached the FDA guidelines by losing 5 percent of their body weight, according to research published in Obesity, the peer-reviewed journal of The Obesity Society.
Still, any obesity drug is going to have to pass much more rigorous long-term safety studies before it catches on. Investors have fresh memories of another obesity drug that was shot down by an FDA advisory panel in June 2007. French drugmaker Sanofi-Aventis gave up on the weight loss drug Acomplia shortly after an FDA advisory panel recommended it be kept off the U.S. market because of studies that suggested it was linked with a higher risk of psychiatric side effects, like depression, anxiety, and suicide risk.
One key difference is that Acomplia is designed to hit a different target on cells, the cannabanoid receptors, specifically CB-1, Behan says. “It’s a completely different mechanism,” Behan says.
Even so, many Big Pharma companies, probably remembering the fen-phen debacle quite well, have chosen to sit on the sidelines with obesity drugs, Behan says. Many decided to scrap their drugs in development against the CB-1 receptor after the Acomplia failure. That’s left three small U.S. biotech companies in the hunt with drugs in late-stage development—Arena, San Diego-based Orexigen Therapeutics (NASDAQ: OREX), and Mountain View, CA-based Vivus (NASDAQ: VVUS). NeuroSearch, a Scandinavian company, also has a drug in late-stage development called tesofensine.
Arena doesn’t see itself being hemmed in by competitors so much as coming up with a great drug that can capture a sizable chunk of such a big market opportunity. “This is such a big problem, it’s not like this is some big race to the market. There’s really very few players,” Behan says. By the end of next month, Arena will have a much clearer idea of whether it’s still in the game.
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