Spinraza Shows Sustained Efficacy Over Years of Use, SHINE Data Find

Years of treatment with Spinraza (nusinersen) show sustained effectiveness, from motor skill gains to disease stabilization, and continued safety across a broad range of spinal muscular atrophy (SMA) patients, from toddlers to young adults, updated findings from the SHINE study show.

The greatest benefits were among children with infantile-onset SMA who began Spinraza before 7 months old, but some with later-onset SMA and treated as teenagers also acquired an ability to sit or stand during SHINE.

These findings, which reach out to 6.5 years for some patients, were to be presented at the 2020 American Academy of Neurology (AAN) annual meeting in late April. That meeting was canceled due to the COVID-19 pandemic, and abstracts are available online.

Spinraza, developed by Biogen, is an approved therapy for all types of SMA that raises levels of full-length survival motor neuron (SMN) protein — which is largely absent or insufficient in SMA patients due to mutations in the SMN1 gene. SMN is essential for the health of motor neurons, nerve cells that control muscle movement.

“As the first approved treatment for SMA, Spinraza offers a significant data set that allows us to uniquely assess the safety and durability of repeated doses over time … across age groups and varying disease severity,” Alfred Sandrock, Jr., MD, PhD, executive vice president, Research and Development at Biogen, said in a press release.

SHINE (NCT02594124) is an ongoing Phase 3 open-label extension study in a range of SMA patients who participated in five previous Spinraza investigational trials, including the Phase 3 trials ENDEAR (NCT02193074) and CHERISH (NCT02292537).

All enrolled are receiving the active treatment. They initially were treated at doses administered in their original trial, but following a protocol change all in SHINE were placed on the recommended Spinraza dose, 12 mg via intrathecal (spinal cord) injection every four months.

This dose follows an initial loading period of four doses, with the first three given every 14 days and the fourth 30 days later.

An interim analysis covering patients who moved into SHINE from ENDEAR — which assessed Spinraza in infants (under 7 months) likely to have type 1 disease — was detailed in the AAN presentation, “Nusinersen in Infantile-onset Spinal Muscular Atrophy: Results from Longer-term Treatment from the Open-label SHINE Extension Study.”

ENDEAR showed significant benefits in motor milestones and respiratory health with Spinraza’s use; it was so successful the trial was stopped early so all would be treated. Findings from SHINE continued to demonstrate the benefits of early treatment with Spinraza in this infantile-onset SMA population.

Based on the October 2018 cutoff date for this analysis, 89 children moved from ENDEAR to SHINE: 65 from the Spinraza group, and 24 from the placebo group.

At the time the recommended dose’s use stated in SHINE, 36% of children who were on Spinraza treatment since ENDEAR were able to sit without support, 8% could stand with assistance, and 5% were able to walk with assistance.

None of those who started Spinraza later — because they were on placebo during ENDEAR — achieved these motor milestones. These children, however, showed evidence of motor function stabilization.

Data relative to a 2019 cutoff was not specified in the study abstract, but the company noted that the trend was similar, with those who began Spinraza earlier experiencing the greatest benefit, while those who started it later “showed evidence of motor function stabilization or improvement.”

An analysis of SMA patients with later-onset disease, who entered SHINE after being enrolled in CHERISH or in the CS2/12 trial (NCT01703988) was in the study, “Longer-term Treatment With Nusinersen: Results in Later-onset Spinal Muscular Atrophy From the SHINE Study.”

At the time of the analysis (October 2018), 125 patients from CHERISH, including 83 on Spinraza and 42 on placebo, as well as 24 from CS2/12, had transitioned to SHINE. Those on Spinraza during CHERISH and SHINE had better motor function — assessed through  Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM) scores — than those previously on placebo in CHERISH.

Children and adolescents with SMA type 3 originally treated in CS2/12 also showed better motor function than those with type 2 disease.

A later data cutoff, done in 2019, included these patients as well as those who transitioned from the Phase 2 EMBRACE (NCT02462759) trial, but details planned for the AAN discussion were not in the study abstract. Biogen, in its release, noted that HFMSE and RULM scores were stable in these individuals, again demonstrating treatment durability.

Seven young adults with types 2 and 3 SMA, who began treatment as teenagers (ages 13–15) during the CS2 trial and its open-label extension CS12, are also now in SHINE. Some have been under treatment for up to six and a half years, and as of October 2018 ranged in age from 19 to 21.

In “Longer-term Experience with Nusinersen in Teenagers and Young Adults with Spinal Muscular Atrophy: Results from the CS2/CS12 and SHINE Studies,” researchers presented data on five of these patients, two of whom were unable to walk when they entered CS2.

Data from 2018 showed the three patients who could walk continued to do so throughout SHINE, while one of the non-ambulatory patients acquired an ability to stand with assistance and the other to sit with support during this trial.

Later 2019 data reported most of these young people continued to experience either stabilized or improving motor abilities in tests measuring motor function.

Spinraza’s use was also seen here to help those caring for SMA patients. Most caregivers reported stable or improved scores across all seven domains of the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND), a tool that measures how neuromuscular disorders affect patients’ caregivers. Domains include physical, emotional, and financial assessments.

Finally, in the presentation, “Safety Profile of Nusinersen in Presymptomatic and Infantile-Onset Spinal Muscular Atrophy (SMA): Interim Results From the NURTURE and ENDEAR-SHINE Studies,” researchers shared data (cutoff March 2019) regarding the safety of Spinraza across babies enrolled in NURTURE Phase 2 trial (NCT02386553) and in ENDEAR.

NURTURE included presymptomatic newborns up to 6 weeks old, and ENDEAR infants up to age 7 months. After almost four years of treatment, Spinraza’s safety profile was seen to be consistent with previous findings. The most common adverse events were fever, respiratory tract infections, and common cold.