Arena Inc. said lorcaserin, the weight-loss drug rejected last month, boosted the risk in obese diabetics of a heart abnormality that was among the reasons U.S. regulators pulled Wyeth’s fen-phen from the market in 1997.
Patients who took the medication lost an average of 4.5 percent of their body weight, compared with 1.5 percent among those taking placebo, the San Diego-based company said in a statement. At the end of the yearlong study, 2.9 percent of patients had valvulopathy, a heart-valve disorder, compared with 0.5 percent of those taking placebos, Arena said. The side- effect data wasn’t statistically significant, the company said.
Arena is racing Vivus Inc., of Mountain View, California, and Orexigen Therapeutics Inc. of San Diego to introduce the first prescription weight-loss drug in more than a decade. The Food and Drug Administration declined to approve lorcaserin on Oct. 22, asking the company for the results of the diabetes trial and data about cancer in earlier studies of rats. John LeCroy, an analyst at Hapoalim Securities, said the drug won’t gain FDA approval and lowered his target price for Arena.
“In our view, any valvulopathy signal is extremely concerning,” LeCroy said today in a note to investors. “In light of lorcaserin’s limited efficacy, the concerns over rodent mammary tumors and the new numerical increase in valvulopathy seen in the BLOOM DM trial, we are removing lorcaserin from our valuation of Arena as we now assume the drug is unapprovable.”
The study had too few patients to reach conclusions about the heart-valve risk, Jack Lief, Arena’s chief executive officer, said today in a telephone interview. Six patients taking lorcaserin in the trial and one patient on placebo had valvulopathy, as measured by echocardiograms, he said.
The difference in the rate of valve defects was smaller between the groups in studies of about 7,200 patients previously submitted to the FDA, according to briefing documents prepared by the agency’s staff. The agency concluded that the studies showed the increased risk of valvulopathy in patients taking the medicine was about 7 percent.
Steve Yoo, an analyst with Leerink Swann & Co. in New York, said he was “encouraged” by the new data and thought the heart results weren’t a big worry for regulators.
“The FDA did not raise concerns about valvulopathy” in its letter last month describing the reasons it didn’t clear the drug, Yoo said today in a note to investors. “This is unlikely to become an issue.”
Arena, which is developing lorcaserin with Tokyo-based Eisai Co., will meet with the FDA to discuss the diabetes study and the rat cancer issue sometime before year’s end, Lief said.
‘Confident’ About Approval
“We’re confident, and so is Eisai, that lorcaserin is approvable,” Lief said in a telephone interview yesterday. “It’s not a question of if, but when.”
Arena lost 5 cents, or 3.3 percent, to $1.48 at 4 p.m. New York time in Nasdaq Stock Market composite trading. The company declined 59 percent in the past 12 months.
Two-thirds of American adults are overweight, raising their risk of diabetes, heart disease, high blood pressure and cancer, according to the 2008 National Health and Nutrition Examination Survey. Within this group, more than one-third are obese, measured as a ratio between height and weight.
Safety concerns have led to the demise of three weight- loss drugs since fen-phen was withdrawn in 1997. Regulators rejected Sanofi-Aventis SA’s rimonabant in 2007 and asked Abbott Laboratories to remove Meridia on Oct. 8.
In Arena’s study, 604 obese or overweight patients who also had Type 2 diabetes took a placebo or a 10-milligram dose of lorcaserin once or twice a day. After one year, 37.5 percent of the patients taking two doses of the medication daily had lost at least 5 percent of their weight, compared with 16.1 percent of patients taking placebo. A weight loss of 10 percent was achieved by 16.3 percent of those taking the drug and 4.4 percent of those taking a placebo.
The findings released by Arena didn’t include results on 95 patients who took only a single daily dose of lorcaserin.
At the start of the study, patients weighed an average of 228 pounds and had a mean body mass index of 36. Their average HbA1C level, a measure of blood sugar, was 8 percent. By the end of the study, the glucose level of the patients taking lorcaserin declined 0.9 percent, compared with a 0.4 percent drop among those taking placebo.
The company’s initial reading of the development of cancer in some rats suggested they weren’t relevant to humans, Lief said. The company will analyze that data again and present their new findings to FDA officials, he said.
Yoo said the company’s ability to address the rat cancer issue may be the most important step toward gaining FDA approval.
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