[Updated: 9:50 am ET] San Diego-based Arena Pharmaceuticals faces a lot of questions that need to be answered before it can hope to win FDA clearance to sell its obesity pill. Now the drug developer says it has at least one piece of the puzzle it hopes will satisfy U.S. drug regulators.
Arena (NASDAQ: [[ticker:ARNA]]) is announcing today that a new study of nine patients shows the obesity drug lorcaserin (Lorqess) enters the cerebrospinal fluid at far lower concentrations in human beings than it does in rats. This latest human trial was designed to answer one of the questions the FDA raised when it turned down Arena’s application last October. The agency, looking at Arena studies that showed an increased risk of brain tumors in male rats on extreme high doses of the drug, raised a theoretical risk that the same might be true in humans, even though it wasn’t observed in clinical trials.
The company suffered a major blow last October when the FDA raised that objection, among others, in turning down Arena’s application. It prevented Arena, and its partner, Eisai Pharmaceuticals, from immediately entering what could be a multi-billion dollar market for a new weight loss pill. The drug passed its clinical trials, which had enrolled more than 7,000 people, although the FDA said Arena’s weight-loss compound offered only “marginal” effectiveness. Besides that, regulators raised questions about the brain tumors in male rats, breast tumors in female rats, and about the compound’s potential for abuse in the marketplace, among other things. Arena has said it is working with the FDA to answer its questions in hopes of re-submitting a revised application by year’s end.
To say a lot is riding on Arena’s re-submission is an understatement. Arena has raised more than $1 billion since its founding in 1997, and it is still hoping that lorcaserin will become its first marketed product.
“This is what the FDA wanted us to do, so we are happy to come out with a win,” says Arena CEO Jack Lief.
[Corrected reference to rat blood concentration.] Here’s what the study was designed to show. It enrolled nine obese patients, who took the Arena drug twice-daily for 7 days, and then they gave blood, and spinal fluid. The drug is designed to stimulate a receptor in the brain that’s thought to make people feel full and stop eating, so researchers believe it has to get into the spinal fluid to work. But too much could be a bad thing. Based on this study, Arena found that about 1.7 times more of the drug gets into the spinal fluid than in the bloodstream. That number gave Arena some comfort, because it is far less than the 24 times greater concentration that was seen in the male rat brains compared with the concentrations seen in rat blood, in rats that had no brain tumor.
Arena’s prior studies of humans only looked at the amount of drug that got into the bloodstream, so it really only had extrapolations of how much of the drug was getting into the spinal fluid. Before this latest study, company estimates were that a higher amount of the drug would get into the human spinal fluid, Lief says.
While Arena says the new study gives it greater confidence that a safe amount of drug is getting into the spinal fluid, it did emphasize that it doesn’t speak for the FDA. In the last line of today’s statement, Arena says, “the FDA also may or may not view the estimates as reliable or predictive of the safety margin.” So this is a story that will take a good while longer to play itself out at the FDA.
