ENCORE, the second Phase III induction trial of Tysabri ( Natalizumab ) for the treatment of moderately to severely active Crohn's disease in patients with evidence of active inflammation, met the primary endpoint of clinical response as defined by a 70 point decrease in baseline Crohn's Disease Activity Index ( CDAI ) score at both weeks 8 and 12.

In addition, ENCORE met all of its secondary endpoints including clinical remission at both weeks 8 and 12. Clinical remission was defined as achieving a CDAI score of equal to or less than 150 at both weeks 8 and 12.

There were no notable differences in the overall rates of adverse events or serious adverse events between the Tysabri and placebo treatment groups.
The most common adverse events seen in the trial were headache, nausea, abdominal pain and nasopharyngitis
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On February 28, 2005, Elan Corporation, and Biogen Idec announced that they voluntarily suspended Tysabri from the U.S. market and all ongoing clinical trials.
This decision was based on reports of progressive multifocal leukoencephalopathy ( PML ), a rare and potentially fatal, demyelinating disease of the central nervous system.
Elan and Biogen Idec's comprehensive safety evaluation concerning Tysabri and any possible link to PML is ongoing.
At the time of the dosing suspension, all ENCORE study patients had completed dosing based on the study protocol and collection and analysis of data followed.

"The results of the ENCORE study are encouraging because patients treated with Tysabri achieved a significant improvement in symptoms of this devastating, chronic immune disease," said Lars Ekman, executive vice president and president, Research and Development, Elan. " Patient safety remains our top priority. We plan to share the data from ENCORE and our other Phase III Tysabri Crohn's studies with the FDA and other regulatory agencies to determine the appropriate path forward for Tysabri as a potential new treatment option for this underserved patient population."

"These data provide further evidence of the benefit of Tysabri in treating immune-mediated diseases. We are committed to a thorough safety evaluation so we can better define the benefit-risk profile of Tysabri. We hope to have findings from the evaluation by the end of the summer," said Burt Adelman, executive vice president, Development, Biogen Idec.

ENCORE was a Phase III, international, double-blind, placebo-controlled study of 510 patients at 114 sites to evaluate the safety and efficacy of intravenous Tysabri in patients with moderately to severely active Crohn's disease ( based on a confirmed diagnosis of Crohn’s disease and a CDAI score of >= 220 and <= 450 ) and evidence of active inflammation ( as evidenced by elevated C-reactive protein (CRP) levels of CRP > 2.87 mg/l, the upper limit of normal ).

Patients were randomized 1:1 to treatment with Tysabri ( 300mg ) or placebo infusions at weeks 0, 4, and 8. Efficacy and safety assessments were performed at weeks 4, 8 and 12, and the study remains ongoing for safety follow-up.

Source: Elan Corporation & Biogen Idec, 2005


XagenaMedicine2005