The European label for Spinraza (nusinersen) has been updated to include longer-term benefits seen in pre-symptomatic treatment of spinal muscular atrophy (SMA), as well as in patients with infantile- and later-onset forms of the disease.
The disease-modifying treatment’s long-term benefits were seen in the Phase 2 studies NURTURE (NCT02386553), in presymptomatic babies, and EMBRACE (NCT02462759), in both infantile and later-onset SMA. The same results were seen across the SHINE Phase 3 trial (NCT02594124), in patients who took part in prior Spinraza investigational studies, and the CS3A Phase 2 study (NCT01839656) of symptomatic children with infantile-onset disease.
“These data confirm the longer-term safety and efficacy profile of nusinersen [Spinraza] and add to the impressive and growing body of clinical evidence including more than 300 patients in a broad range of ages and types of SMA,” Ivana Rubino, Biogen’s executive medical director and global head of neuromuscular medical affairs, said in a press release.
Results from NURTURE, as of March 2019, with a patient median age of approximately three years, show that all 25 children treated were able to sit without support, and most (22) to walk unassisted in a normal timeframe. These children were treated earlier than 6 weeks of age, and were most likely to have SMA type 1 or 2. No toddler has required permanent ventilation.
The SHINE study showed that initiating treatment earlier leads to greater benefits. But it also demonstrates that starting on Spinraza at a later stage still leads to significant improvements in motor function and ability to conduct daily activities. SHINE has been following infantile-onset patients who took part in the ENDEAR Phase 3 study (NCT02193074), and later-onset participants of the Phase 3 CHERISH (NCT02292537) trial.
Data shown at the recent American Academy of Neurology (AAN) 2019 annual meeting, from an October 2018 interim analysis, revealed that starting treatment before an infant was 6 months old led to a greater proportion of children able to sit without support (60% vs. 38%) than first taking Spinraza after this age. Receiving Spinraza in both trials also was associated with longer periods without needing permanent ventilation compared with starting the therapy in SHINE only.
In line with these findings, later-onset patients who had participated in CHERISH — most likely to have type 2 or 3 SMA — had greater motor function benefits if they had been on Spinraza over the two trials, and if they were treated at a younger age.
As of SHINE’s latest review, patients who transitioned from CHERISH had been taking Spinraza for up to 1.2 years, while those from ENDEAR were on the therapy for up to 1.5 years.
The label also addresses findings from EMBRACE, a two-part trial with 21 infants not eligible for ENDEAR and CHERISH. All patients on Spinraza were alive, and did not require permanent ventilation as of the early termination of Part 1. Motor function improvements associated with Spinraza were seen in 7 of 9 children with infantile-onset SMA, and in 4 of 5 participants with the later-onset form of the disease.
Motor benefits also were observed in the CS3A trial, with 12 of 20 children showing significant improvement in the ability to achieve motor milestones — including kicking, grasping, controlling the head, rolling, sitting, crawling, standing, or walking. In addition, 11 patients had an increase in total CHOP-INTEND motor scores of at least 4 points. At the last study visit, 11 patients were alive, and free of permanent ventilation.
Through Spinraza’s commercial use, its Expanded Access Program, and clinical trial participants, more than 7,500 infants, teens, and adults have been treated with the therapy worldwide, Rubino said. The company also is working to create global SMA registries and real world data initiatives, which will provide long-term information on SMA and its treatment, she added.