RARE Daily

Biogen Reports New Spinraza Data in SMA

April 19, 2021

Rare Daily Staff

Biogen reported initial data from the Spinraza clinical development program that examined using higher doses of the therapy to optimize outcomes for people with the rare neurodegenerative condition spinal muscular atrophy, which supports continued development of the higher dose regimen.

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

Spinal muscular atrophy (SMA) is a rare, genetic, neuromuscular disease that affects individuals of all ages. It is characterized by a loss of motor neurons in the spinal cord and lower brain stem, resulting in progressive muscle atrophy and weakness. SMA is caused by a deficiency in the production of survival motor neuron (SMN) protein due to a damaged or missing SMN1 gene, with a spectrum of disease severity. Some individuals with SMA may never sit; some sit but never walk; and some walk but may lose that ability over time. In the absence of treatment, children with the most severe form of SMA would not be expected to reach their second birthday.

Spinraza is an antisense oligonucleotide (ASO) that targets the root cause of SMA by continuously increasing the amount of full-length survival motor neuron (SMN) protein produced in the body. It is administered directly into the central nervous system, where motor neurons reside, to deliver treatment where the disease starts. Spinraza is approved to treat infants, children, and adults with spinal muscular atrophy and is available in more than 50 countries. 

Building on the efficacy and 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 12-milligram (mg) dose of Spinraza to the higher dose.

An analysis of the higher loading and maintenance dosing regimen in Part A showed no new safety concerns in study participants who were followed for up to approximately five months. There were no adverse events reported that were considered related to the higher dose study drug and there were no severe or serious adverse events. Four patients reported mild or moderate adverse events, including ones considered related to the treatment administration procedure.

The company said this emerging safety profile supports 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 50 mg two weeks apart followed by 28 mg maintenance doses every four months) compared to the approved 12 mg dose of Spinraza: four loading doses, followed by maintenance doses every four months.

The company is also 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 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. Measuring neurofilament levels have been integrated as an exploratory endpoint in the DEVOTE and RESPOND studies.

Biogen also said it has developed a conceptual clinical framework to evaluate the potential value of Konectom, a mobile application, to enable adults living 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.

 “We continue to be driven by the pursuit of better outcomes for patients, including exploring the potential of a higher dose of Spinraza in the DEVOTE study, in addition to initiating the RESPOND study,” said Alfred Sandrock, Jr., head of research and development at Biogen. “We are also evaluating the use of biomarkers and digital tools to supplement traditional clinical assessments for SMA and enhance disease monitoring. Through these collective research efforts, we aim to provide valuable data that may help guide future treatment approaches and decisions for people with SMA.”

Photo: Alfred Sandrock, Jr., head of research and development at Biogen


Stay Connected

Sign up for updates straight to your inbox.