SMA is a neurodegenerative disease caused by mutations in the SMN1 gene, which provides instructions to make the survival motor neuron (SMN) protein. Although humans have another gene — SMN2 — capable of producing SMN, a slight difference in its DNA sequence results in 90 percent of these proteins being shorter and nonfunctional.
Spinraza, developed by Biogen, is the only approved treatment for all types of SMA in countries that include the U.S., the European Union, Brazil, Japan, Switzerland, Australia, South Korea, Canada and Chile. It increases the ability of the SMN2 gene to produce a full-length SMN protein, restoring its levels and function.
Results from part 1 of the EMBRACE clinical trial (NCT02462759), titled “Safety and Efficacy of Nusinersen in Infants/Children with Spinal Muscular Atrophy (SMA): Part 1 of the Phase 2 EMBRACE Study,” will be shown as a scientific poster on April 23.
EMBRACE is a randomized, double-blind Phase 2 study evaluating Spinraza’s safety and tolerability in 21 infants/children with SMA who didn’t qualify to participate in the ENDEAR (NCT02193074) or CHERISH (NCT02292537) trials.
Exploratory goals included achievement of motor milestones — based on the Hammersmith Infant Neurological Examination (HINE) Section 2 — reduction in ventilator use, and changes in growth parameters.
Participants were randomized to receive 12 mg of Spinraza (14 patients) or a placebo (seven patients), and divided according to age at onset: 6 months old or younger, and older than 6 months.
Results showed that Spinraza continued to be safe and well-tolerated, with a similar safety profile to the ones observed in previous studies.
Seventy-nine percent of patients receiving Spinraza achieved key motor milestones, compared with 29% of patients in the placebo group. Spinraza-treated patients had smaller increases in the hours of ventilator use over the course of the study than patients receiving placebo.
No differences in weight gain and body length increase were found between the two groups.
Part 1 of the EMBRACE trial was ended early after the ENDEAR study showed strong positive results, and all participants, including those in the placebo group, were able to transition to the open-label, Phase 3 SHINE study (NCT02594124), where all patients receive Spinraza.
Another study, “Ambulatory function and fatigue in nusinersen-treated children with spinal muscular atrophy,” to be shown as a scientific poster on April 23, evaluated the effects of Spinraza in the walking ability and fatigue of children with SMA type 2 and type 3.
Researchers analyzed the data of patients who participated in a Phase 1/2 trial (NCT01703988) evaluating the safety profile of escalating doses (3 mg, 6 mg, 9 mg, and 12 mg) of Spinraza for 85 days, who were later enrolled in an ongoing Phase 1 extension study (NCT02052791) evaluating a 12 mg dose of Spinraza for 533 days.
Walking ability and fatigue were assessed based on the six-minute walk test in the 14 patients who were able to walk during both trials. The test was taken at the beginning of the first study, after 253 days and again after 1,050 days.
Patients’ mean age of symptom onset was 23.9 months and 8.6 years at the time of screening for the study. Participants increased their median distance walked by 17 meters at day 253, and by 99 meters at day 1,050. This was accompanied by a reduction in mean fatigue of 0.1% at day 253 and 3.8% at day 1,050.