Treatment Aids Survival, Motor Milestones in Patients With Infantile-Onset SMA

Nusinersen improved survival and attainment of developmental motor milestones over 3 years in patients with infantile-onset spinal muscular atrophy, according to a study published in The Lancet Child & Adolescent Health.

“Nusinersen showed a favorable benefit–risk profile in participants with infantile-onset spinal muscular atrophy at the interim analysis of a phase 2 clinical study,” researchers explained in the background section of the study, which was funded by Biogen and Ionis Pharmaceuticals. “We present the study’s final analysis, assessing the efficacy and safety of nusinersen over 3 years.”

Twenty infants, between ages 3 weeks to 6 months, with two or three SMN2 gene copies and infantile-onset spinal muscular atrophy were enrolled in the study. Participants in the first cohort received multiple intrathecal loading doses of 6 mg equivalent nusinersen, and those in a second cohort received multiple loading doses of 12 mg dose equivalent. Afterward, both cohorts received maintenance doses of 12 mg equivalent nusinersen.

Among 19 evaluable participants, 63% reach the study’s primary endpoint of incremental improvement in motor milestones assessed using the Hammersmith Infant Neurological Examination section 2 (HINE-2), researchers reported.

Subgroup analyses showed that participants with two SMN2 copies treated with 12 mg nusinersen had a steady increase in HINE-2 motor milestone total score, from a mean 1.46 at baseline to 11.86 at day 1135.

Researchers characterized the 3-year safety profile as favorable.

“At study closure (August 21, 2017), 15 (75%) of 20 participants were alive,” they wrote. “One hundred one serious adverse events were reported in 16 (80%) of 20 participants; all five deaths (one in cohort 1 and four in cohort 2) were likely to be related to spinal muscular atrophy disease progression.”

Reference:
Finkel RS, Chiriboga CA, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: final report of a phase 2, open-label, multicentre, dose-escalation study. The Lancet Child Adolesc Health. 2021;5(7):491-500. doi:10.1016/S2352-4642(21)00100-0