Treatment with Spinraza (nusinersen) results in greater improvements in motor function and continues to improve or stabilize motor function scores in spinal muscular atrophy (SMA) patients, according to recent clinical data.
The findings were presented during the 2019 American Academy of Neurology (AAN) Annual Meeting, being held in Philadelphia.
The open-label SHINE (NCT02594124) trial is primarily assessing Spinraza’s long-term safety and tolerability, while also analyzing improvements in motor function and event-free survival, which included death and length of time with no need for respiratory support. Its participants took part in prior clinical trials of Spinraza.
The study, “Interim Report on the Safety and Efficacy of Longer-Term Treatment With Nusinersen in Infantile-Onset Spinal Muscular Atrophy (SMA): Updated Results From the SHINE Study,” presented by Richard S. Finkel, addressed preliminary results from SHINE in 89 patients with infantile-onset SMA followed for up to four years.
These participants were most likely to develop type 1 disease and transitioned from the double-blind, placebo-controlled ENDEAR Phase 3 study (NCT02193074). Among them, 65 had received Spinraza in both ENDEAR and SHINE and 24 were controls in ENDEAR but received Spinraza in the SHINE trial.
Treatment with Spinraza resulted in additional or new motor function improvements on CHOP INTEND scores, which measure motor skills.
As of Oct. 15, 2018, children who had received Spinraza in both trials increased their average CHOP INTEND score by 16.8 points after almost three years of treatment, while those who received placebo in the ENDEAR trial, and were more advanced in their disease, still increased their scores by 8.2 points after more than 1.5 years of treatment.
“This degree of improvement is remarkable and it really does reflect a very significant improvement in motor function for these infants,” Wildon Farwell, executive director of clinical development at Biogen, said in an interview with SMA News Today.
“To be able to see an eight-point improvement in [patients who began treatment only during SHINE trial], to be able to see continuous, long-standing improvement in the patients who began treatment in ENDEAR, really sets the mark for what Spinraza can achieve,” he said.
As Farwell noted, 8- and 16-point improvements are well above what the field describes as clinically meaningful (4-point improvement). “You’re talking about improvement in multiple domains, you’re talking about improvement in multiple limbs or multiple functions. It’s not that a patient is only improving in one area of their body, they’re improving in different areas. It really is a meaningful improvement.”
Both those who began treatment before and after 6 months of age (younger and older group) were able to sit without support (60% and 38%, respectively). However, those who were younger upon treatment initiation showed greater improvements in CHOP INTEND scores (19.4 vs. 13.8 points in older group).
These children also showed improved event-free survival rates compared to the natural history of the disease. Patients who received Spinraza in both trials had a longer period of survival without need for permanent ventilation (median of 1.4 years) than those who only initiated treatment in the SHINE study (median of 5 months).
Among children who began Spinraza treatment only in SHINE and were alive without permanent ventilation at the beginning of the study, more than half (58%) remained alive without permanent ventilation at the data cutoff.
There were no new safety findings. Levels of liver enzymes remained low, indicative of a favorable liver function. Among the most frequent adverse events were fever and upper respiratory tract infection. However, none were considered related to treatment.
“Each milestone in these studies marks a new chapter in what it means to live with SMA, and the insight provided is invaluable in understanding the long-term experience of this rare disease,” Alfred Sandrock Jr., MD, PhD, executive vice president and chief medical officer at Biogen, said in a press release.
Additionally, the study, “Interim Report on the Safety and Efficacy of Longer-term Treatment With Nusinersen in Later-onset Spinal Muscular Atrophy (SMA): Results From the SHINE Study,” presented as a scientific poster by Basil T. Darras, reported baseline and early findings from patients with later-onset SMA, who were most likely to develop type 2 or 3 SMA and transitioned from the Phase 3 CHERISH (NCT02292537) trial.
In this patient population, changes in motor function were assessed via the achievement of World Health Organization (WHO) milestones, the Hammersmith Functional Motor Scale – Expanded (HFMSE), and the Revised Upper Limb Module.
The median age at first Spinraza dose or sham procedure was 43.3, 58.2, and 49.7 months, and median age at symptom onset was 11, 11, and 10 months in the 42 patients who were controls in CHERISH (50% females), the 42 who were controls but received Spinraza in SHINE (50% females) and the 84 who received the therapy in both trials (55% females), respectively.
At baseline, mean WHO motor milestones score was 1.5, 1.4, and 1.4, while mean HFMSE score was 19.9, 19.8, and 22.4, respectively.
Participants are now being dosed with 12mg of Spinraza every four months and have been followed for up to four years.
As of Oct. 15, 2018, mean change in HFSME score from the beginning of the study was 3.7 for children who were treated with Spinraza in SHINE and CHERISH. This contrasted with a positive 0.4 change among participants in the CHERISH sham-control group and who later on went to receive Spinraza in the SHINE trial.
Participants who did not receive Spinraza in the CHERISH trial saw a 0.4 decline in HFSME scores.
There was a continued benefit, either improvement or stabilization, for Spinraza on motor function scores in most patients, especially those who received the therapy at a younger age (younger than 3.69 years): four children in this group were walking independently at day 690 compared to no patients at baseline.
Motor function improved, then stabilized, in children who received Spinraza at an intermediate age (between 3.69 and 4.92 years) and stabilized in those who were older (older than 4.92 years upon first dose).
Safety findings were consistent with those previously reported for Spinraza and there were no treatment-related serious adverse events and no patient has discontinued treatment due to an adverse event.
“These results confirm previous data from our trials, which demonstrated that early treatment with Spinraza can make a critical difference in survival and achieving motor milestones. The data also demonstrate that improvements in motor milestones were achieved in individuals who began treatment with Spinraza at a later age. This is a powerful development for the SMA community,” Sandrock said.