Biogen has shared new data from the Spinraza (nusinersen) clinical development program aimed at optimizing outcomes for people with SMA and advancing understanding of the disease.

Exploring Opportunities to Optimize Treatment in SMA
Building on the proven efficacy and well-established safety of Spinraza in a broad range of patients with SMA, the Phase 2/3 DEVOTE study is evaluating the safety, tolerability, and potential for even greater efficacy of Spinraza when administered at a higher dose than currently approved. The three-part study includes an open-label safety evaluation cohort (Part A), a pivotal, double-blind, active control randomized treatment cohort (Part B), and an open-label cohort (Part C) transitioning from the approved 12mg dose of Spinraza to the higher dose.

An analysis of the higher loading and maintenance dosing regimen in Part A (n=6; 28mg) showed no new safety concerns in study participants who were followed for up to approximately five months (64-158 days). There were no adverse events (AEs) reported that were considered related to the higher dose study drug and there were no severe or serious AEs. Four patients reported mild or moderate AEs, including AEs considered related to the treatment administration procedure. This emerging safety profile supports Biogen’s continued development of a higher dose of Spinraza, including ongoing enrollment of patients in the pivotal Part B of the DEVOTE study. This part will evaluate the higher-dose regimen (2 loading doses of 50mg two weeks apart followed by 28mg maintenance doses every four months) compared to the approved 12mg dose of Spinraza: four loading doses, followed by maintenance doses every four months. More information about DEVOTE is available at ClinicalTrials.gov (NCT04089566).

Using Biomarkers and Digital Tools to Enhance Disease Monitoring
Biogen is advancing research to evaluate biomarkers and digital tools that expand on traditional clinical assessments and incorporate more sensitive measures to help better predict and monitor the course of SMA.

New data in patients (n=75) from the CHERISH/SHINE studies build upon the body of evidence suggesting neurofilament levels—an indicator of ongoing biological disease activity—warrant further evaluation as a biomarker for treatment response in SMA. Data show that higher neurofilament levels at baseline were, on average, associated with greater improvements in motor function scores among Spinraza-treated individuals with later-onset SMA over a median of approximately four years. The use of biomarkers could improve the understanding of disease mechanisms and interventions for SMA and other neurological diseases. Therefore, measuring neurofilament levels have been integrated as an exploratory endpoint in the DEVOTE and RESPOND (NCT04488133) studies.

Additionally, in consultation with SMA experts, Biogen has developed a conceptual clinical framework to evaluate the potential value of Konectom™, a mobile application, to enable adults with SMA to quantitatively and remotely self-assess motor function in their daily lives. Currently used only in research settings, Konectom leverages smart sensing technologies like touchscreen and accelerometry to capture tangible data in studying neurological diseases. In SMA, monitoring fatigue and smartphone typing skills may be useful to assess functional impact across a broad range of patients with varying levels of disease severity. Biogen is also studying Konectom’s potential utility in multiple sclerosis and other neurological diseases, with the goal of providing a more accurate and complete picture of how neurological diseases impact a person’s daily life.

These data are being presented at the American Academy of Neurology (AAN) 2021 Virtual Annual Meeting, April 17-22.