Panel Backs Approval of Second Biologic for Ulcerative Colitis

In the second study, which followed patients for 1 year and included some who had been treated with infliximab (40%), the clinical remission rate at 8 weeks was 16.5% among those on adalimumab, vs. 9.3% among those on placebo, a 7.2% difference that was statistically significant. At 52 weeks, the remission rate was 17.3% among those on adalimumab, vs. 8.5% among those on placebo, an 8.8% difference that also was statistically significant.

In different votes, the panel nearly unanimously agreed that the 8 week and 52 week clinical remission rates in the studies represented "clinically meaningful benefits."

However, in the second study, 8.5% of the patients on adalimumab were in clinical remission at both weeks 8 and 52, vs. 4.1% among those on placebo. The panel was less unanimous about whether the 4.4% difference between the two groups represented a clinically meaningful benefit of treatment, voting 10-6 with 1 abstention on this question.

Other findings in the 52-week study included a higher steroid discontinuation rate among those on adalimumab, a secondary endpoint: About 13% of those on adalimumab were able to go off steroid treatment before the 52nd week of treatment and had achieved a clinical remission, compared with 5.7% of those on placebo, a statistically significant difference. In addition, the patients on azathioprine or 6-MP at baseline in this study did not appear to benefit from adalimumab: In this subgroup, the remission rate at week 8 among those on adalimumab (12.9%) was similar to the rate among those on placebo (15%). But for those who were not on the immunomodulatory drugs at baseline, the remission rate was nearly 19% among those on adalimumab vs. 6.6% of those on placebo, the FDA reviewer pointed out. In the studies, the safety profile of adalimumab was similar to the placebo, other than a higher rate of injection site reactions among those on adalimumab, and no new safety signals for adalimumab were identified in the trials, according to Abbott.

If the FDA grants approval, adalimumab will be the only self-administered biologic therapy available for patients with UC, the company pointed out. In April 2012, adalimumab was approved in the European Union for treating adults with moderately to severely active UC who have had an inadequate response to conventional therapy, based on the same data submitted to the FDA for the UC indication, according to Abbott.

The company is planning an international registry of patients with UC treated with adalimumab in typical clinical settings to collect long-term safety data, which will include patients in the EU, and, if approved, in the United States. The FDA usually follows the recommendations of its advisory panels, which are not binding. The company expects a decision on approval by the end of the year, according to an Abbott spokesperson.

Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.