Nusinersen Treatment of Spinal Muscular Atrophy Provides Continued Motor Development and Studies Will Evaluate a Higher Dose
Continued development and studies of nusinersen (Spinraza; Biogen, Cambridge, MA), the first of several treatments for spinal muscular atrophy (SMA) developed in just the last 5 years, show sustained survival and improvement in motor function. Studies also suggest a higher dose may be more effective for some people with SMA.
In the NURTURE study (n=25) (NCT02386553), 92% of presymptomatic infants treated with nusinersen maintained the ability to swallow after a median 3.8 years. Participants were consistently rated by their caregiver as having, on average, never-to-rare difficulty with most measures related to feeding, drinking liquids, and eating solid foods. All participants with 3 SMN2 copies and 73% (11 of 15) with 2 SMN2 copies are feeding exclusively by mouth according to caregiver reports.
“Intervention with SPINRAZA can meaningfully impact the trajectory of SMA, and we remain relentless in our aim of improving outcomes for people with SMA. We continue to better understand and explore SPINRAZA’s potential with our new and ongoing global clinical studies,” said Alfred Sandrock, Jr., MD, PhD, Head of Research and Development at Biogen. “The data at Cure SMA 2021 demonstrate the long-term benefits with SPINRAZA as individuals age. Additionally, a new analysis provides further support for the potential for a higher dose of SPINRAZA to offer even greater improvements in motor function for SMA patients.”
Analysis of data from the phase 2 CS3A trial (NCT01839656) and the phase 3 ENDEAR (NCT02193074) study used pharmacokinetic/pharmacodynamic modelling to calculate the possible efficacy of a higher dose of nusinersen. Both studies were done with participants who had infantile-onset SMA. A higher dose of nusinersen may lead to a clinically meaningful increase in the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) score. This is being tested in the DEVOTE study, which has 3 cohorts. The first is an open-lable safety cohort, treated with 28 mg of nusinersen every 4 months after 2 loading doses of 50 mg. This cohort of 6 participants has been treated, and no new safety signals have been observed.
The second cohort is a group of participants who are being randomly assigned to receive 12 or 28 mg of nusinersen every 4 months after 2 loading doses of 50 mg. There is also a third, open-label group of participants who have been receiving 12 mg every 4 months who will be transitioned to 28 mg every 4 months.