Nusinersen-Treated Patients With SMA Experience Unprecedented Survival

Kathryn Swoboda, MD

New results from the phase 2, open-label NURTURE study (NCT02386553) of nusinersen (Spinraza; Biogen) suggest that in infants with genetically diagnosed spinal muscular atrophy (SMA) experienced unprecedented survival rates with treatment up to 4.8 years, with patients continuing to maintain and achieve gains in motor function compared to SMA natural history.¹

As of February 2020, 100% of patients treated in the study were alive and free of the need for permanent ventilation. The study data, which included 25 patients (median age, 3.8 years) over the longest assessment period of pre-symptomatic patients, are expected to be presented at the virtual Cure SMA Research and Clinical Care Meeting.

“The impact of early and sustained Spinraza treatment on these infants and their families is remarkable. I’ve had the privilege to watch them grow into active young children, many of whom have experienced progress in motor function consistent with children their age who do not have SMA,” Kathryn Swoboda, MD, Katherine B. Sims Endowed Chair in Neurogenetics, and director, Neurogenetics Program, Massachusetts General Hospital, said in a statement. “The new results from NURTURE continue to bolster the substantial benefit of both prompt diagnosis and early and longer-term treatment with Spinraza.”

In addition to the aforementioned achievements, the updated analysis showed that all study participants who were previously able to walk with assistance (92%) and walk independently (88%) maintained that ability over the 11 months since the last data cut. As well, over 11 months of follow-up, 1 child gained the ability to walk with assistance—pushing the mark to 96%of all study participants—and also reached the maximum score on the Children’s Hospital of Pennsylvania Infant Test of Neuromuscular Disorders (CHOP-INTEND) scale, thus increasing the total number of study participants who achieved the maximum score to 84% (n = 21).

READ MORE: Cure SMA Announces New Funding for Network of SMA Research and Treatment Centers

Those with 2 copies of SMN2 were also observed to be able to score and advance on the Hammersmith Functional Motor Scale Expanded scale (HFMSE), inconsistent with natural history.

Overall, the Biogen therapy was considered well-tolerated, and no new safety concerns were identified, nor have any children discontinued the study due to adverse events (AEs) associated with treatment. NURTURE is still ongoing, and has been extended by an additional 3 years, allowing Biogen to evaluate the longer-term efficacy and safety through 8 years of age and further understand the impact of early treatment.

Earlier this year, results from 2 datasets from the open-label SHINE extension study (NCT02594124) of nusinersen revealed that treatment with the agent results in sustained efficacy and long-term safety in 2 other subgroups of patients with SMA—infantile-onset and later-onset. Those data were accepted to the American Academy of Neurology (AAN) 2020 Annual Meeting.^2,3

The first dataset included 83 participants from the CHERISH study (NCT02292537) who received nusinersen and 42 from the sham-procedure group who transitioned to SHINE, as well as 24 from the CS2/12 study (NCT01703988). The analysis was conducted by Claudia A. Chiriboga, MD, MPH, professor of neurology, Columbia University Irving Medical Center, and colleagues.²

Using October 15, 2018, interim data cut from SHINE, HFMSE score at the modified maintenance dosing regimen (MMDR) Day 1 for patients with later-onset SMA (MMDR Day 240 visit) was 26.0 (standard deviation [SD], 11.01) for those who received nusinersen in CHERISH/SHINE (n = 61) and 21.2 (SD, 7.75) for those randomized to sham-procedure in CHERISH and then nusinersen in SHINE (n = 36).

The mean Revised Upper Limb Module (RULM) scores at MMDR Day 1 for these groups were 23.4 (SD, 5.54), and 21.2 (SD, 4.31) for the nusinersen-nusinersen and sham/nusinersen group, respectively. Additionally, the mean HFMSE at MMDR Day 1 was 33.2 (SD, 12.26) for those with SMA type II who transitioned from CS2/12 (n = 9) and 56.2 (SD, 6.85) for those with SMA type III (n = 13). The study also revealed the mean RULM scores at MMDR Day 1 were 26.4 (SD, 4.81) for the type II patients (n = 8) and 36.7 (SD, 0.58) for the type III patients (n = 3), respectively.

In the second dataset, 36% of patients (21 of 59) with infantile-onset SMA who received nusinersen in ENDEAR/SHINE achieved the World Health Organization (WHO) motor milestone of sitting without support. Of the 59 patients included in the study, 8% (n =5) achieved standing without assistance and 5% (n = 3) were walking with assistance at MMDR Day 1. Results showed that no patients who were randomized to the sham-procedure in ENDEAR and nusinersen in SHINE (n = 22) achieved any of these milestones.³

That set included 65 participants from the ENDEAR nusinersen-treated study and 24 from the sham-procedure group who transitioned to SHINE. Participants from CS3A, ENDEAR and EMBRASE could transition to SHINE. Those from CS3A and EMBRACE directly entered the MMDR period or transitioned to the MMDR at their next study visit if they were already participating in SHINE. Mean HMFSE at MMDR day 1 was 7.3 (SD, 6.82) for patients who received nusinersen in ENDEAR/SHINE (n = 50) and 0 for patients randomized to the sham-procedure in ENDEAR/nusinersen in SHINE (n = 17).

In a recent NeurologyLive Cure Connections segment, Crystal Proud, MD, considered the possibility of incorporating neuromuscular treatments for SMA with Philippa Cheetham MBChB, MRCS, MD, and a patient, Sebastian Mills. Watch her discuss the impacts that trials such as NUTURE have had below.

REFERENCES

1. New Results From Landmark NURTURE Study Show That Pre-Symptomatic SMA Patients Treated With SPINRAZA® (nusinersen) Continue to Demonstrate Sustained Benefit From Treatment [press release]. Cambridge, MA: Biogen; Published June 10, 2020. Accessed June 10, 2020. globenewswire.com/news-release/2020/06/10/2046158/0/en/New-Results-From-Landmark-NURTURE-Study-Show-That-Pre-Symptomatic-SMA-Patients-Treated-With-SPINRAZA-nusinersen-Continue-to-Demonstrate-Sustained-Benefit-From-Treatment.html

2. Chirboga CA, Darras BT, Farrara MA, et al. Longer-term treatment with nusinersen: results in later-onset spinal muscular atrophy from the SHINE study. Neurology. 2020;94(15 Suppl):166

3. Castro D, Finkel RS, Farrar MA, et al. Nusinersen in infantile-onset spinal muscular atrophy: results from longer-term treatment from the open-label SHINE extension study. Neurology. 2020;94(15 Suppl):1640.