FDA questions safety of potential Crohn’s disease, colitis treatment

The FDA’s Center for Drug Evaluation and Research focused on potential risks related to vedolizumab in a document released in advance of the drug being considered by a joint meeting of the Gastrointestinal Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee Monday in Washington.

The panels will discuss the biologics license applications for vedolizumab (Entyvio, Takeda Pharmaceuticals) as therapy for adult patients with moderately to severely active ulcerative colitis and/or Crohn’s disease who have had insufficient response to or were intolerant to conventional therapy or a tumor necrosis factor-alpha antagonist.

“The key safety issue is the risk of progressive multifocal leukoencephalopathy (PML), which could potentially be caused by vedolizumab,” the Center for Drug Evaluation and Research briefing document said. “There is uncertainty about the adequacy of the safety database to provide an acceptable pre-marketing assessment of this risk of PML.”

PML is a rare, usually fatal, viral brain disease that tends to attack people with depressed immune systems.

There were no cases of PML during the development of vedolizumab, the briefing said, but vedolizumab’s function is similar to that of natalizumab (Tysabri, Biogen Idec), which has been associated with PML.

“The applicant asserts that vedolizumab does not have the same risk of PML as natalizumab because of mechanistic differences between the two products (mainly differences in receptor binding targets), and that in vitro activity data, animal models and human pharmacodynamic data suggest a lower PML risk than for natalizumab,” the document said. “FDA reviewers have questioned if this data provide sufficient evidence of less risk of PML than natalizumab.”

Healio.com will cover the meeting Monday.