By Terri Somers
UNION-TRIBUNE STAFF WRITER
March 18, 2008
Arena Pharmaceuticals said yesterday an independent safety monitoring board found the company's experimental obesity drug, lorcaserin, was safe and did not cause any heart valve problems after 12 months.The second safety review in a year may help San Diego-based Arena attract a commercialization partner for the drug that was discovered in-house and developed alone.
The Echocardiographic Data Safety Monitoring Board had monitored 3,200 clinical trial participants using the drug because it hits the same receptor in the brain as the weight loss drug Fen-phen, which was popular in the 1990s. That receptor affects the feeling of fullness after meals.
But one of the two components of the drug made by Wyeth, fenfluramine, also hit a second target in the heart, which was linked to heart valve problems. The drug was pulled from the market in 1997, costing Wyeth millions of dollars.
The markets responded favorably to the Arena news, at least initially. Shares rose 12 percent to $7.08 early in the day, but closed up 3 percent at $6.50.
This critical milestone assessing month-12 echocardiographic data strongly supports lorcaserin's cardiovascular safety profile, Arena Chief Executive Officer Jack Lief said in a statement.
The echocardiographic safety board previously had given Arena good news after testing patients at six months.
We believe that this exposure duration, even under a conservative interpretation of the literature, would have been sufficient to observe a fenfluramine-like effect on heart valves if present, Lief said.
Literature from previous studies of fenfluramine showed that possible heart valve problems would show up early in the trial, Chief Science Officer Dominic Behan said.
Good safety data can only help Arena attract possible partners in the commercialization of lorcaserin, Behan said.
We've had some high hurdles to overcome, and this is a significant milestone in that regard, Behan said.
The safety board will not meet again on this drug, but Arena will continue to collect heart safety data after 18 months and 24 months of the two-year study known as the Bloom trial.
The primary efficacy goal of the trial is to learn the number of patients with a 5 percent or greater weight reduction from baseline at week 52 as compared to placebo.
We want to establish a very broad and robust safety data set, Behan said.
Banc of America Securities analyst William Ho said in a note to clients that he believes passing the 12-month safety hurdle is significant, as we found the majority of primary care physicians prescribe obesity drugs for a six-to 12-month period according to our June 2007 survey.
Oppenheimer & Co. analyst Bret Holley said the data should place Arena in a stronger position to negotiate a major marketing partnership for the drug, although the timing of such a partnership agreement is uncertain.
Holley said Arena shares are substantially undervalued at a price of less than $12.
Patients in the second of three lorcaserin trials have begun enrollment, Behan said. Known as the Blossom trial, it will be for one year and include people previously diagnosed with valvulopathy, a heart valve disorder, he said.
A third Phase 3 trial for lorcaserin, for people with type 2 diabetes, is now under way.
Final data from the trials are expected in 2009. The company hopes to file a new drug application with the Food and Drug Administration before the end of 2009, Behan said. If approved, lorcaserin would be Arena's first marketable product and has the potential to be a first in its class drug for the treatment of obesity.
Several other companies, including San Diego-based Amylin Pharmaceuticals and Orexigen Therapeutics, are striving to bring obesity drugs to market.
Amylin's obesity therapy, pramlintide, is in midstage clinical trials.
Pramlintide is a synthetic analog of amylin, a neurohormone secreted by the pancreas that plays a role in the regulation of appetite, food intake and glucose concentrations after meals. It is the active ingredient in Symlin, a diabetes drug Amylin has on the market.
Orexigen's experimental therapy, Empatic, is in Phase 3 clinical trials. It is a combination of two drugs the FDA has approved for different uses: zonisamide, an anti-convulsant, and bupropion, an anti-depressant. Orexigen has combined the two in a suspended-release form.
Each drug targets pathways in the brain's hypothalamus that mediate appetite and energy expenditure.
Drug industry experts predict that an effective weight-loss drug could generate more revenue than billion-dollar cholesterol drugs.
The Associated Press contributed to this report.