FDA reviewers question Humira benefit in UC

FDA reviewers questioned whether Humira adalimumab from Abbott Laboratories (NYSE:ABT) provides a "clinically meaningful benefit" for ulcerative colitis (UC) patients given the drug's "serious" safety risks and the availability of Remicade infliximab for the indication. Reviewers said Humira provides only a "marginal" effect on induction of remission rates compared to placebo, and a lesser effect on sustained remission rates. The reviewers did say that Humira, which is administered subcutaneously, may provide an additional convenience benefit over Remicade, which is given via IV. However, the reviewers cautioned that moving patients from Remicade to the "potentially less effective" Humira, while still exposing them to comparable safety risks, is a "concern." Both products are mAbs against TNF alpha. The comments came in briefing documents released ahead of Tuesday's meeting of the Gastrointestinal Drugs Advisory Committee to discuss an sBLA for Humira.

FDA raised similar concerns in a complete response letter last November. In March, Abbott submitted additional post hoc analyses, but reviewers said Friday that the analyses were of "questionable value" and "difficult to interpret" because the endpoints and comparisons were not prospectively defined. FDA reviewers also said a higher dose should be studied, citing data showing that a higher exposure in Humira resulted in an increased remission rate. Abbott did not conduct Phase II dose-finding studies of Humira in UC patients, but rather used the dose approved for Crohn's disease. Reviewers added that a study demonstrating a benefit in any subgroup of patients "could increase our confidence" that Humira should be approved for UC. ...