Reeling from setbacks in obtaining approval for its Lorqess diet pill, Arena Pharmaceutical is laying off 66 employees - about 25 percent of its workforce - and continues to maintain that a resubmission can be filed with the FDA by the end of the year. However, the drugmaker could not guarantee the deadline can be met and offered a laundry list of issues to first resolve with FDA staffers.
The list includes what the drugmaker deemed as "non-clinical issues" involving ties between Lorqess and tumors in rats, a notion that has plagued Arena executives for months, especially after Arena ceo Jack Lief was criticized for failing to more thoroughly vet the topic with investors prior to the rejection by the FDA advisory panel last September (see this).
In a statement, Arena says five independent pathologists were retained to relates to review "the diagnostic uncertainty" in classifying mammary masses in female rats. The next involves demonstrating a mechanism for mammary adenocarcinoma in female rats that "is reasonably irrelevant to human risk," which requires experiments "to further test the theory" that Lorqess causes mammary tumors in rats by increasing prolactin. The FDA suggested Arena consider a 12-month study.
The third issue concerns the unidentified method of action and unclear safety margin for brain astrocytoma in male rats. To satisfy the FDA, Arena plans what it calls a small clinical study and "non-clincal" experiments. Interestingly, the drugmaker will also expand the study to further assess the risk of valvulopathy, which is heart-valve disease.
You may recall that the mechanism in Lorqess is similar to the mechanism in fenfluramine. Both are designed to block appetite signals in the brain. And this was the half of the fen-phen weight-loss cocktail that Pfizer’s Wyeth recalled in 1997 - along with a chemically similar pill called Redux - due to a fatal lung disease and heart-valve problems (read more here).
Arena has a lot of work to do and, now, fewer people to help meet its deadlines. The layoffs should save $13 million in annual costs, but Lief is under pressure to salvage its deal with Eisai, which paid $50 million for the rights to sell Lorqess in the US; another $160 million based on development and approval milestones, and a $1.16 billion, one-time payment that may follow based on annual sales. Can Arena pull it off or is it just another fat chance?
pic thx to alan cleaver on flickr