NewsSpeak: natalizumab SPMS trial is negative

We need to learn why the ASCEND trial was negative; we owe it SPMSers! #NewsSpeak #MSBlog #MSResearch

"Biogen have just made a press release stating that the natalizumab in SPMS or ASCEND trial was negative. I predicted based on the length-dependent axonopathy hypothesis that this trial would be negative in relation to lower limb function, but not upper limb function. This prediction was based on the short duration of this trial (24 months)."

"I am very interested in doing a post-hoc analysis of this study. Could it be positive if early lower limb progressions (EDSS and timed-25ft walk progressions within the first 12 months), which are pre-programmed by previous damage, are excluded from the analysis; i.e. these study subjects are kept in the study looking for second progressions? However, the limiting factor is this study was its duration; it was simply too short. It is a great pity it was not an adaptive, event-driven, stydy that ran for 36+ months. I suspect the open cheque-book associated with these event-driven trials makes it too expensive and risky for Pharma."

"I really feel for all the SPMSers who were hoping for this study to be positive. The fact that this study delayed disease progression in the upper limbs is excellent news. It means inflammation is alive and kicking in the SPMS phase of  the disease and that it is worthwhile continuing to look for effective treatments to target this phase of the disease. Don't forget upper limb function is as important, if not more important than lower limb function, to preserve if you have SP or PPMS."

"I would like to thank Biogen for taking on the challenge of SPMS. I hope your next SPMS trial is designed differently to learn the lessons of the ASCEND trial." 


Secondary Progressive Multiple Sclerosis from Gavin Giovannoni

Excerpts Businesswire

.... The Phase 3 ASCEND study investigating natalizumab in the treatment of secondary progressive multiple sclerosis (SPMS) did not achieve its primary and secondary endpoints...


.... Given the challenges of treating this advanced stage of MS, these results underscore the importance of treatment early in the course of disease with effective disease-modifying therapies before a patient advances to SPMS....

.... 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 .....


..... SPMS 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..... 


CoI: multiple

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