The phase 3 ASCEND study investigating Natalizumab ( Tysabri ) in the treatment of secondary progressive multiple sclerosis ( SPMS ) did not achieve its primary and secondary endpoints. During the study, Natalizumab was generally well tolerated and adverse events were consistent with its known safety profile.
ASCEND evaluated the efficacy and safety of Natalizumab to slow the accumulation of disability progression unrelated to relapse in SPMS patients, an unmet medical need. The majority of study participants had EDSS scores of 6.0 to 6.5 ( walking aid required ) and were non-relapsing for two years prior to enrollment in the study.
The study’s composite primary endpoint evaluated the percentage of patients whose disability had progressed on one or more of three disability measurements comprising the composite endpoint.
Natalizumab demonstrated a statistically significant effect on upper limb function ( one of the three components of the primary composite endpoint ) unrelated to relapses. Consistent with the established effects of Natalizumab in relapsing multiple sclerosis, analyses of exploratory endpoints suggest that some patients received a benefit from treatment, including reduction of relapses and new MRI lesions.
Secondary progressive multiple sclerosis is characterized by ongoing nerve damage or loss and patients experience disability progression with increasingly less frequent relapses. Despite extensive clinical research, treatment options for patients with SPMS are extremely limited and none have demonstrated efficacy in slowing the progression of disability unrelated to relapse.
In the United States, Tysabri is indicated as monotherapy for the treatment of patients with relapsing forms of multiple sclerosis. In the European Union, it is indicated as a single DMT in highly active relapsing-remitting multiple sclerosis for adult patients who have high disease activity despite treatment with a beta-Interferon or Glatiramer acetate or patients with rapidly evolving severe RRMS. ( Xagena )
Source: Biogen, 2015