Arena Pharmaceuticals Inc. and Eisai Co. said a study showed that concentrations of their weight-loss pill were lower in human brains than in rat models, a finding that may ease concerns that the drug may be linked to brain tumors.
The U.S. Food and Drug Administration last October rejected the medicine, lorcaserin, for marketing approval and requested more data after a rat study showed a possible link to brain tumors. San Diego-based Arena and Tokyo-based Eisai plan to submit the study to the FDA to support an application for approval.
Lorcaserin is one of three experimental medicines competing to become the first obesity drug approved by regulators in more than a decade. Orexigen Therapeutics Inc. of La Jolla, California, said in June that it would stop development of its pill, Contrave, after the FDA asked for a large study on heart risks. Regulators in October also declined to approve Qnexa from Mountain View, California-based Vivus Inc. and asked for more information about potential birth defects.
In the test of lorcaserin patients, an analysis of plasma and cerebrospinal fluid showed human brains had 1.7 times the exposure to the drug found in the plasma, the companies said today in a statement. That compares with a finding in rats at about 24 times plasma exposure. The results suggest that humans are less likely to grow astrocytomas, slow-growing brain tumors seen in rats tested with the drug, said Christen Anderson, Arena’s vice president of development for lorcaserin.
“Previously, when we submitted our application, we estimated a certain level of risk,” Anderson said in an interview. “What we’re now saying is that the risk to humans relative to rats is a lot lower than previously estimated.”
Brain tumors were found in male rats given certain doses of lorcaserin over a two-year study period. Because the drug may enter human brains differently from rat brains, the relationship of plasma concentration to brain concentration was measured in nine healthy obese volunteers in the seven-day study.
“This means of course that we provide a higher safety margin” than was thought earlier, said Jack Lief, the chief executive officer of Arena, in a telephone interview. The companies will submit their response to the FDA by the end of the year, he said.
Regulators also asked the companies to assess the risk of mammary tumors in female rats. More information on that data will be discussed during Arena’s quarterly earnings call scheduled Aug. 9, Lief said.