FDA questions the safety of Takeda's blockbuster-hopeful bowel disease drug

FDA staff has taken issue with Takeda Pharmaceutical's vedolizumab, warning that the treatment for inflammatory bowel diseases could put patients at risk for a rare but deadly brain infection, possibly outweighing its benefits.

According to an FDA review, Takeda's drug had positive effects on ulcerative colitis and Crohn's disease but carries the risk of progressive multifocal leukoencephalopathy (PML), an often fatal brain virus that afflicts patients with immune deficiency. An agency advisory panel is set to rule on vedolizumab on Dec. 9, and, in documents released ahead of the meeting, FDA staff asks the committee to take a hard look at whether the drug's benefits excuse its risks.

But the agency's safety concerns amount to a sort of guilt by association: None of the patients in Takeda's pivotal trial came down with the disease, but vedolizumab works similarly to Biogen Idec's ($BIIB) Tysabri, an anti-inflammatory that carries a black-box label tied to PML, and that's enough to alarm the FDA. Takeda claims that mechanistic differences between the two drugs make vedolizumab safer, but agency staff isn't convinced that's borne out in the data.

On the efficacy side, the drug nailed its primary and secondary endpoints for ulcerative colitis, and while it beat out placebo in a second trial on Crohn's disease after flunking a prior study, it still missed its secondary goals for that indication. The FDA took little issue with vedolizumab's ulcerative colitis results but questions whether the drug has proven itself in Crohn's, and, worst-case scenario, the agency could restrict its indications and demand Takeda undergo a costly premarket safety study to hammer out the PML risk.

However, FDA staff reviews tend to err on the side of harshness, and the panel is not beholden to agree with its briefing documents, much as the agency is not required to follow the recommendations of its advisers. Regulators are expected to make a final ruling on vedolizumab by Feb. 18.

The drug, a holdover from the Millennium buyout, is targeted at patients for whom TNF-alpha blockers like Remicade and Humira have failed. It's one of 6 drugs Takeda expects to get approved next year, and the company is counting on its leukocyte-targeting antibody to snag a sizeable share of the inflammatory bowel disease market.

- read the briefing (PDF)

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