Elan Corp, plc (DUBLIN, Ireland) and Biogen Idec (CAMBRIDGE, Massachusetts) announced the approval of a supplemental Biologics License Application (sBLA) by the US FDA for Tysabri® (natalizumab) for inducing and maintaining clinical response and remission in adult patients with active moderate-to-severe Crohn's disease, with evidence of inflammation, who have had an inadequate response to, or are unable to tolerate, conventional therapies and TNF-α inhibitors. Tysabri will be available for the treatment of Crohn's upon the completion of key implementation activities related to the approved risk management plan. The companies anticipate the drug will be available to Crohn's patients by the end of February 2008.

The approval is accompanied by "robust labeling with safety warnings," and a Crohn's specific risk management plan (including the mandatory Tysabri Outreach: Unified Commitment to Health Prescribing Program) designed to inform prescribers, patients, and infusion centers about the use of Tysabri and to minimize potential risk of progressive multifocal leukoencephalopathy (PML) and other opportunistic infections. The TOUCHâ„¢ Prescribing Program was developed in conjunction with the FDA to facilitate appropriate use of Tysabri and to assess, on an ongoing basis, the incidence and risk factors for PML and other serious opportunistic infections associated with the treatment. The program already has been implemented for patients receiving the steroid for multiple sclerosis (MS).

Data from the ENCORE trial showed that Tysabri induced response and remission in patients with active moderate-to-severe Crohn's disease, and objective evidence of inflammation, as measured by elevated C-reactive protein. After 12 weeks of therapy, 60% of steroid patients attained response compared with 44% of placebo-treated patients; 48% of steroid-treated patients had sustained response at both weeks 8 and 12 compared with 32% of placebo-treated patients (P <.005 for both). Among those who had inadequate response to prior treatment with TNF-α inhibitors, 38% achieved sustained response at weeks 8 and 12.

Data from ENACT-2 showed that an additional year of Tysabri therapy sustained response and remission rates in patients who had drug response after 3 months in ENACT-1. Steroid responders in ENACT-1 sustained a 61% response rate during ENACT-2 at every visit through an additional 6 months of therapy, compared with 29% for those on placebo. Treatment difference was also sustained through 12 months of additional therapy (54% vs 20%). Remission was sustained at every visit with an additional 6 or 12 months of Tysabri in 45% and 40% of patients, respectively, compared with 26% and 15% of placebo-treated patients (P <.005 for all comparisons). Among patients who had previously failed TNF-inhibitors, response and remission rates were sustained at every visit through an additional 6 months of the drug in 52% and 30% of patients, respectively. Among Tysabri patients achieving a clinical response, approximately two thirds were able to discontinue treatment within 10 weeks of tapering down the drug.

Tysabri increases the risk of PML, an opportunistic viral infection of the brain that usually leads to death or severe disability. Serious opportunistic and other atypical infections have been observed in Tysabri-treated patients, some of whom were receiving concurrent immunosuppressants. Clinically significant liver injury has been reported in patients treated with the drug in the postmarketing setting.

Tysabri has previously been approved for relapsing forms of MS in the US and relapsing-remitting MS in the EU. The drug is also approved for MS in Switzerland, Canada, Australia, New Zealand and Israel; it was discovered by Elan and is codeveloped with Biogen Idec.