Biogen Ends Testing of Tysabri to Treat Strokes After Study Failure

MS drug did not improve patient outcomes compared with placebo

Biogen Inc. says it will not develop natalizumab (Tysabri) for the treatment of acute ischemic stroke after the medication failed a phase 2b trial.

Natalizumab, which made nearly $2 billion in 2017 sales, is part of Biogen’s franchise of multiple sclerosis (MS) drugs, a Reuters report noted. Biogen’s MS portfolio, which is led by top-selling drug dimethyl fumarate (Tecfidera), faces mounting competition from other treatments.

Analysts had viewed Biogen’s plans to develop natalizumab for stroke as risky, and they were unsurprised by the trial’s failure. It is “likely to have limited impact, as our sense had been that expectations were quite low,” said RBC Capital Markets analyst Brian Abrahams.

Ischemic strokes require immediate medical attention and occur when blood supply is cut off to part of the brain.

In the phase 2b, dose-ranging ACTION 2 study in individuals with acute ischemic stroke, Biogen said, natalizumab did not demonstrate improvement in clinical outcomes compared to placebo. Both doses of natalizumab were generally well tolerated and no new or important safety signals were observed. The results of the study do not impact the benefit-risk profile of natalizumab in approved indications, including MS.

ACTION 2 was a multicenter, double-blind, placebo-controlled, randomized study with a 90-day follow-up to evaluate the safety and efficacy of natalizumab primarily in patients with moderate-severity acute ischemic stroke (AIS). The study investigated natalizumab versus placebo in approximately 270 individuals who had a clinical diagnosis of AIS with last known normal (LKN) no more than 24 hours prior to treatment initiation. The study evaluated a 300-mg dose and a 600-mg dose versus placebo, both either within nine hours of LKN or between nine and 24 hours after LKN.

The primary objective of ACTION 2 was to assess the effects of natalizumab compared with placebo on clinical measures of independence and activities of daily living. The primary endpoint was a composite global measure of functional disability based on a score of 0 to 1 on a modified Rankin scale (mRS) and a score of at least 95 on the Barthel Index (BI) at Day 90. The mRS measures independence with specific tasks pre- and post-stroke. BI is a scale that consists of 10 items that measure activities of daily living and mobility.

Detailed phase 2b ACTION 2 study findings will be made available in a future scientific forum.

Natalizumab was previously evaluated in AIS in the phase 2a ACTION study. In this study, although natalizumab did not significantly decrease the primary endpoint of infarct volume at day 5, secondary and exploratory endpoints suggested natalizumab treatment improved clinical outcomes compared with placebo, which warranted further evaluation.

Sources: Reuters; February 7, 2018; Biogen; February 7, 2018.