Crohn’s Disease Drug Safety Review by FDA, WASHINGTON The investigational biologic vedolizumab being submitted for the treatment of Crohn’s disease and ulcerative colitis comes with safety concerns, FDA reviewers said.
In a briefing document released Thursday in advance of Monday’s joint FDA advisory committee meeting to consider whether to recommend approval of the drug, reviewers said their primary safety concern with both indications for the drug is risk of PML [progressive multifocal leukoencephalopathy], noting that there is uncertainty about the adequacy of the safety database to provide an acceptable pre-marketing assessment of the risk of PML.
The Gastrointestinal Drugs and Drug Safety and Risk Management advisory committees will consider applications by vedolizumab’s manufacturer, Takeda Pharmaceuticals, for two different indications: one for adult patients with moderately to severely active ulcerative colitis who are inadequately treated with, do not respond to, or are intolerant to conventional therapy or a tumor necrosis factor-alpha antagonist; and a second for adults with moderately to severely active Crohn’s disease with the same contraindications for tumor necrosis factor-alpha antagonists.
Currently approved treatments for ulcerative colitis include 5-aminosalicylates such as mesalamine (Canasa, Pentasa) and sulfazine (Azulfidine), immunomodulators such as azathioprine (Azasan, Imuran) and 6-mercaptopurine (Purinethol), corticosteroids such as prednisone (Cortan, Deltasone) and methylprednisolone (Medrol), and the biologic agent infliximab (Remicade), as well as surgical interventions.
Approved treatments for Crohn’s disease include fiber supplements, acetaminophen (Tylenol), 6-aminosalicylates, corticosteroids, azathioprine, 6-mercaptopurine, antibiotics, and biologics such as certolizumab (Cimzia), adalimumab (Humira), and natalizumab (Tysabri). Crohn’s disease can also be treated with bowel resection and other surgical interventions.
“We question if, given the potential risk of PML, the appropriate indicated population should be patients that have been tried on steroids only or patients that have been tried on at least immunosuppressants,” FDA reviewers wrote.
The reviewers also questioned the drug’s efficacy in Crohn’s disease, specifically whether “substantial evidence of efficacy has been established for induction of clinical remission.” They noted that only one of the two trials for the indication met its primary endpoint.
In two of the phase III trials, the drug was significantly associated with clinical remission of ulcerative colitis and Crohn’s disease at week six (P
The advisory panel will vote on whether to recommend the drug for approval for either indication, in addition to several other topics.
The FDA is not obligated to follow the recommendations of its advisory committees, but often does.