GAITHERSBURG, Md. -- FDA advisers have recommended approval of the problem-ridden multiple sclerosis drug natalizumab (Tysabri) for treatment of moderate to severe Crohn's disease, but only with extensive safety monitoring.
GAITHERSBURG, Md., Aug. 2 -- FDA advisers have recommended approval of the problem-ridden multiple sclerosis drug natalizumab (Tysabri) for treatment of moderate to severe Crohn's disease.
The advisers said, however, that the drug should be subject to "strict post marketing surveillance." The FDA is not obligated to follow the advisers' recommendations, although it often does.
The approval recommendation, which came in a 12-to-three vote with two abstentions, was at odds with a review by FDA staffers.
In briefing documents, staff analysts questioned the efficacy of the drug, noting that clinical trial data suggested that natalizumab added no benefit beyond currently available Crohn's treatments.
In addition to the negative review from FDA staff, the European Union had previously rejected the drug as a Crohn's treatment, concluding that the drug's benefits did not outweigh its risks.
Nonetheless, advisory panel chair David Sachar, M.D., of Mount Sinai School of Medicine in New York, was unambiguous in his support of natalizumab, pointing out that fewer than 30% of Crohn's disease patients achieve adequate control with available drugs.
Moreover, Dr. Sacher said, testimony from Crohn's patients and treating physicians along with quantitative quality of life data and objective risk assessment data provided evidence of benefits "that I think transcend simple p-values."
But Judith Kramer, M.D., M.S., of Duke University, challenged Dr. Sacher, noting that her reading of the data suggested there was no evidence of efficacy of natalizumab as induction therapy and only one trial that offered "statistically significant" evidence of benefit.
Data from that trial, she pointed out, were difficult to interpret because 30% of the patients were on concomitant immunosuppressive therapy.
Natalizumab was approved for treatment of relapsing multiple sclerosis in November, 2004. But in February 2005 it was withdrawn by its maker, Biogen Idec, and distributor, Elan, after three patients in clinical trials developed progressive multifocal leukoencephalopathy (PML), a rare viral infection of the brain. Two of the cases were fatal. At the same time, the FDA stopped clinical trials of the drug.
The drug was returned to the market in June 2006 under a strict risk management program. (See Tysabri (natalizumab) Allowed Back to Market with Restrictions)
There were no cases of progressive multifocal leukoencephalopathy reported in the Crohn's trials, but the FDA staff reviewers pointed out that because the disease presents with neurological signs and symptoms, it might be less readily identified by gastroenterologists.
The FDA staff analysts said natalizumab was also "associated with an increased incidence of atypical and serious infections; these included viral meningitis, herpes infections, and atypical pulmonary and gastrointestinal infections."