SILVER SPRING, Md. -- An independent panel of FDA advisers overwhelmingly rejected AbbVie's bid to gain approval of Humira (adalimumab) for treatment of active nonradiographic axial spondyloarthritis in adults with signs of inflammation by elevated CRP or MRI.
After rejecting adalimumab by a 12-1 vote with one abstention, the Arthritis Advisory Committee split 7-6 with one abstention when polled about recommending approval of UCB's Cimzia (certolizumab) for treatment of active axial spondyloarthritis, including ankylosing spondylitis (AS).
Adalimumab is already approved for treatment of rheumatoid arthritis, plaque psoriasis, ulcerative colitis, ankylosing spondylitis and psoriatic arthritis, and certolizumab is indicated for Crohn's and rheumatoid arthritis.
Members of the advisory committee sided with an FDA review that found the single trial supporting approval enrolled a high proportion of patients with ankylosing spondylitis skewing results. Those AS patients performed better than patients with radiographic evidence of spondyloarthritis.
"This is a trial about subpopulations, so without a clear definition, it's very difficult to judge the current data," Daniel Solomon, MD, MPH, a rheumatologist at Harvard Medical School in Boston, said. Solomon said he would like an additional clinical trial that clearly defined the subpopulation.
In the study, 192 patients were given either adalimumab or placebo, and after 12 weeks, patients taking adalimumab showed significant improvement over placebo, 36% versus 15% (P<0.001).
In a post-hoc breakdown of patients, combining confirmed and nonconfirmed nonradiographic axial spondyloarthritis would increase the treatment difference to 15%.
"I think the criteria were too loose to define a population that will likely benefit," Donald Miller, PharmD, chair of pharmacy practice department at North Dakota State University in Fargo, said.
Nancy Lane, MD, director of the Center for Musculoskeletal Health at the University of California at Davis School of Medicine, noted there was an improvement in symptoms from a certain population group even if it were defined ad hoc.
Patient representative Michael Tracy Smith of New York City was the only panelist who voted for approval.
Committee members voted 10-4 in favor of the safety. The FDA noted the safety profile resembled that of the known profile of the drug approved more than a decade ago.
Members that voted No said it was because the drug -- which carries a boxed warning for certain malignancies and infections -- would be unsafe in a population where it's not effective.
But the panel members said the case was not as clear cut when it considered the certolizumab application.
"I think overall, we agree there is definitely an efficacy signal here, and the question is more about limitation in the real world," committee chair Tuhina Neogi, MD, PhD, professor of epidemiology at Boston University Schools of Medicine and Public Health, said.
As with adalimumab, the panel said different subgroups of patients responded differently to the drug.
In a randomized, controlled trial of more than 300 patients, 58% of patients taking 200 mg of certolizumab showed improvement, compared with 38% of those taking placebo (P=0.004), . For those taking 400 mg of certolizumab, 64% showed improvement (P<0.001).
Several committee members said the FDA could work with the manufacturer, Belgium drugmaker UCB, to create a better definition and label so providers know who is best to receive the drug.
No drug is indicated to treat nonradiographic axial spondyloarthritis. An exact deadline for an FDA decision on either drug isn't known.
The FDA isn't obligated to rely on the opinions of its advisory committees but usually does.