Spinal muscular atrophy treatment Zolgensma was found to be safe and effective for long-term use and use in presymptomatic patients, according to posters presented at the 2021 MDA Virtual Clinical & Scientific Conference.
Studies presented at the 2021 MDA Virtual Clinical & Scientific Conference demonstrated positive safety and efficacy results for gene therapy onasemnogene abeparvovec-xioi (Zolgensma) used long term and in patients with presymptomatic spinal muscular atrophy (SMA).
Investigators for the SP1NT trial, an ongoing multicenter, open-label phase 3 study, presented some early safety and efficacy results for 2 presymptomatic patient cohorts: a group of patients with 2 copies1 of the survival motor neuron 2 (SMN2) gene and a cohort of patients with 3 copies2.
SMA type 1, a form of the disease in which patients can’t sit up without support, presents during infancy in about 97% of patients with 2 copies of SMN2, which leads to death in a median of 13.6 months if left untreated. Similarly, 85% of patients with 3 copies of SMN2 have SMA symptom onset during infancy and often are unable to walk without support.
In the group of patients with 2 copies of SMN2, asymptomatic patients anticipated to develop SMA received the 1-time therapy intravenously and will be evaluated through 18 months.
As of June 11, 2020, 14 patients were enrolled. At their most recent visit, the median age of the patients was 15.60 months and the median time to follow-up was 14.85 months. No patients died and none have required ventilatory or feeding tube support as of their last visit.
Eleven patients achieved the primary endpoint of sitting up without support for 30 seconds or longer. In addition, 10 of the 11 were developing at a normal rate, similarly to patients who do not have SMA. All patients achieved motor function improvement scores of 50 or greater.
Every patient experienced at least 1 adverse event, with131 in total; 22 were treatment related in 10 patients. While 5 patients experienced a serious adverse event (AEs), accounting for 7 in total, all serious AEs eventually resolved and were deemed unrelated to the treatment. No AEs resulted in study discontinuation.
The cohort of patients with 3 copies of SMN2 includes 15 patients who will be evaluated through 24 months after receiving treatment. At the time of their most recent visit (June 11, 2020), no deaths or use of ventilatory or feeding tube support had occurred. At the time of the visit, their median age was 15.20 months and the follow-up visit was occurring at a median of 14.50 months.
Eight patients achieved the primary endpoint of standing unassisted for 3 seconds or longer within the normal developmental window of 16.90 months. The remaining 7 patients were all younger than 16.90 months at their last visit.
Further, 6 patients were able to walk alone within the normal development window of 17.6 months; the other patients were all under 17.6 months of age at their last visit.
AEs were experienced by all patients, amounting to 120 in total. Seven patients had a combined 26 treatment-related AEs and 2 patients experienced 1 serious AE each. Both serious AEs resolved and were determined to be unrelated to treatment. No AEs resulted in study discontinuation.
The START trial3 is a phase 1 study evaluating the long-term safety and efficacy outcomes of onasemnogene abeparvin 13 patients with SMA type 1. The oldest patients (n = 3) received a low dose of the drug. The youngest patients (n = 10) received a therapeutic dose of the drug.
Overall, 8 patients experienced serious AEs. All serious AEs were considered unrelated to treatment and did not result in study discontinuation.
Patients who received a therapeutic dose survived and did not require permanent ventilation. The patients in this group either maintained all of the milestones they attained previously or achieved new milestones. Two patients advanced to achieve standing with assistance without requiring concomitant nusinersen (Spinraza) at any point.
Additionally, after 4 years after dosing, 6 patients in this group did not need to receive daily respiratory support. Nusinersen therapy was still present in 7 out of 13 patients.
As of June 11, 2020, 6 patients were enrolled in another related study evaluating long-term outcomes that will be completed in 2035.