For the past few months, Arena Pharmaceuticals ceo Jack Lief has been at the center of controversy over the extent to which the drugmaker’s Lorqess diet pill may have links to tumors in rats and, more specifically, whether data about this possibility was disclosed correctly. Last September, he was chastised for not conveying any info prior to disclosure that was made publicly by FDA staffers, who discussed the data in documents submitted for an FDA advisory panel.

After the panel voted down the drug, he argued that “we believe that (Lorqess) does not pose a cancer risk to humans at the recommended therapeutic dose…There is an immense amount of data generated in drug development. We did not, and still do not believe that the data’s relevant to humans and, as such, did not believe it was material to investors.” He made those remarks in a conference call with investors and maintained the FDA panel simply did not understand the data (back story).

Maybe not, but the agency made an issue of tumors and rats when a Complete Response Letter was issued (see this). This, of course, forced Arena to acknowledge the concern (see here). And as we now know, the FDA wants Arena to conduct several analyses to clarify any links between tumors and rats (background here).

But there is a disconnect. In a meeting last month with analysts, Lief maintained Arena could resubmit its filing with the FDA by the end of 2011 (read here). And in a statement late last week in which plans were disclosed to eliminate 25 percent of its workforce, Arena reiterated that pledge (read it here). Yet the same statement noted the FDA wants the drugmaker to “consider performing a separate 12-month study in female rats” to determine ties to mammory tumors. So how can the 2011 target date be met?

And last November, a trial in 604 patients with diabetes indicated 2.9 percent of the people on Lorqess developed valvulopathy, which is heart-valve damage, compared with just 0.5 percent on a placebo. This raised separate concerns because Lorquess is designed to hit one of the same receptors as fen-phen, the notorious diet-pill combo that was withdrawn in 1997 over heart damage. One component, fenfluramine, and Lorqess are designed to hit the same 5-HT2B receptor class in the brain, although each was conceived to hit different receptors.

But the issue for the agency is whether this is too close for comfort, which is why Arena last week acknowledged that receptor studies will be expanded to “more fully characterize” how Lorqess interacts with the 5-HT2B receptor in order to determine the risk of valvulopathy. However, as the Forbes Medicine Show notes, Arena had insisted back in November that valvulopathy was already addressed, even though the trial for diabetes patients was not powered to “detect meaningful differences in the incidence of valvulopathy.”

All of which is to say that Arena, which is led by Lief, of course, seems to have a difficult time gauging the extent to which there are concerns that must be addressed in order for the FDA to approve Lorqess. There may be a difference of opinion over data, but it is generally not debatable that satisfying the agency is necessary to obtain approval. And being clear with investors is part of the process, which led the Medicine Show to ask whether Lief should go. What do you think?

 Loading ...