Treatment with nusinersen improved motor function up to 5 years in infantile-onset SMA

Treatment with nusinersen led to continued and improved motor function up to 5 years after initial dose in infants with spinal muscular atrophy, according to a poster presented at the International Scientific Congress on Spinal Muscular Atrophy.

“The long-term follow-up in the SHINE study allows us to better understand the new emerging phenotypes in SMA,” Diana Castro, MD, founder and director of the Neurology and Neuromuscular Care Center and the Neurology Rare Disease Center in Dallas, told Healio. “Without a well-designed and controlled study, physicians would not be able to counsel our new patients and their families in what to expect and what is realistic as they navigate life with SMA.”

Castro and colleagues sought to examine the safety and efficacy of nusinersen, an antisense oligonucleotide for adults and children with infantile-onset spinal muscular atrophy, who transitioned from the ENDEAR study into the SHINE study. ENDEAR is a sham-controlled, phase 3 trial lasting up to 394 days of nusinersen in symptomatic infantile-onset patients likely to have SMA Type 1, while SHINE is an ongoing, open-label extension study.

A total of 105 participants were given nusinersen in the SHINE study (80 having started treatment in ENDEAR, 25 started in SHINE) with a median time on study of 5.3 years. Participants were analyzed in three groups by age at first study dose and timing of first dose: Aged younger than 6 months and previously received nusinersen or sham procedure in ENDEAR (n = 51); aged 6 months to younger than 10 months and previously received nusinersen or sham procedure in ENDEAR (n = 29); and aged 10 months to younger than 23 months and started nusinersen in SHINE after receiving sham in ENDEAR (n = 25).

According to results, mean Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores improved from baseline to day 1,538 across all age groups (aged < 6 months, 27 to 48.3; aged 6 to < 10 months, 25.9 to 43.8; aged 10 to < 23 months. 17.4 to 25.2), while Revised Upper Limb Module and Hammersmith Functional Motor Scale Expanded scores also continued to improve within the two youngest groups from baseline to day 1,080.

In addition, no serious adverse events were considered related to treatment as of the data cut-off date. The most common adverse events were pyrexia, pneumonia and upper respiratory tract infections, while the most common serious adverse events included pneumonia, respiratory distress and respiratory failure.

“The SHINE study results show that patients continue gaining motor function and reaching milestones after an average of 5 years of treatment, without significant side effects in up to 7 years of follow-up,” Castro told Healio. “With any therapy, it is important to be able to continue hoping for new motor milestones, even if they may be delayed.”