Sma - Treatment

Abstract

Neuromuscular Disorders 31 (2021) S47-S162 treatment was ongoing in 7/13 patients. As of November 12, 2020, 31 patients (IV cohort, n = 23; IT cohort, n = 8) were enrolled in LT-002. One patient in each cohort reported SAEs, and one AESI was reported in the IV cohort (treatment-unrelated). None required permanent ventilation and 9 patients reported baseline respiratory support. Among patients for whom motor milestone data are available from baseline visits as of the data cutoff, 11 new milestones that were not achieved in the parent study were achieved for 4 patients, all in the IV cohort. The highest new milestone achieved in the 4 IV cohort patients was sitting without support. Enrollment is ongoing in LT-002. A single IV administration of onasemnogene abeparvovec at the therapeutic dose provided a sustained, durable response for up to 5.6 years since dosing for patients up to 6.1 years of age. There have been no reported treatment-related SAEs or AESIs, supporting a favorable benefit-risk profile.

The impact of three SMN2 gene copies on clinical characteristics and effect of disease-modifying treatment in patients with spinal muscular atrophy: a systematic literature review

“…Similar primary endpoint results were seen in the patients with two SMN2 copies, with 14/14 of these patients (100%) achieving independent sitting at any visit up to 18 months of age (90). However, while 93% of patients with three SMN2 copies achieved independent standing within the World Health Organization (WHO) developmental window (87), this endpoint was achieved by 50% of patients with two SMN2 copies (90), and the median time to independent walking was 422 days in those with three copies vs. 493 days in those with two copies (87, 90). All 15 of the patients with three SMN2 copies treated with onasemnogene abeparvovec were alive and free from permanent ventilation at the end of the study (87).…”

“…Strauss and colleagues reported a subgroup analysis from the phase 3 SPR1NT study in presymptomatic infants at risk of developing SMA who had three SMN2 copies (n = 15) (87). They did not directly compare outcomes in treated patients with three vs. two SMN2 copies, because the primary study endpoint was different between groups (independent sitting at any visit up to 18 months of age in those with two SMN2 copies vs. independent standing within 24 months of age in those with three SMN2 copies) (90). All 15 infants with three SMN2 copies achieved the primary endpoint (independent standing for ≥3 s at any visit up to 24 months of age); the median time to this milestone was 377 days, and 14/15 (93%) achieved independent standing within the normal developmental window, compared with 24% in the Pediatric Neuromuscular Clinical Research (PNCR) natural history study (p < 0.0001).…”

Diving into progress: a review on current therapeutic advancements in spinal muscular atrophy

“…The key clinical manifestations include muscle weakness, atrophy, and hypotonia. Patients with SMA may also exhibit respiratory difficulties, joint contractures, and scoliosis (42). It is essential to recognize these clinical signs early, as timely intervention can significantly impact the prognosis and quality of life for affected individuals.…”

Sleep and sleep-related breathing disorders in patients with spinal muscular atrophy: a changing perspective from novel treatments?

“…In the STR1VE study, 20 out of 22 patients were free of permanent ventilation at the age of 14 months, while in the START study all patients in the therapeutic-dose cohort were free of permanent ventilation at the age of 24 months, in striking contrast with natural history studies. Initiating treatment in presymptomatic patients has demonstrated the potential to yield a more favorable prognosis of both motor development and respiratory function (92). Real-world and extension studies evidence showed favorable respiratory outcomes (93)(94)(95)(96)(97).…”