Nusinersen Shows Efficacy in Infantile- and Late-Onset Spinal Muscular Atrophy


The new data further cemented the therapy’s consistent safety profile from previous studies as well as demonstrated a newfound durability in patients with later-onset spinal muscular atrophy.

Claudia Chirboga, MD, MPH

Claudia Chirboga, MD, MPH

Results from 2 datasets from the open-label SHINE extension study (NCT02594124) of nusinersen (Spinraza; Biogen) revealed that treatment with the agent results in sustained efficacy and long-term safety in patients with both infantile-onset and later-onset spinal muscular atrophy (SMA).

The first dataset that was accepted to the American Academy of Neurology (AAN) 2020 Annual Meeting 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.

Using the October 15, 2018, interim data cut from SHINE, Hammersmith Functional Motor Scale-Expanded (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).1

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.

As for the other data subset that was accepted to AAN 2020 Annual Meeting, 21 of 59 (36%) patients 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, 5 (8%) achieved standing without assistance and 3 (5%) 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.2

The study 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 each of the 2 datasets from SHINE, patients received the MMDR of nusinersen 12 mg every 4 months. Participants initiated the MMDR at the end of the SHINE blinded loading dose period or 120 days after date of last loading period dose.

Nusinersen became the first FDA approved drug for the treatment of SMA in pediatric and adult patients in December 2016. The approved recommended dosage of the injection is 12 mg per intrathecal administration.3

Biogen recently announced that the first patient had been treated in the DEVOTE global clinical study (NCT04089566). Researchers will test the effects of nusinersen in a broad range of patients with SMA while exploring a higher maintenance dose of 28 mg. NeurologyLive caught up with Richard Finkel, MD, principal investigator of the study to provide further details.


1. 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

2. 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.

3. FDA approves spinraza (nusinersen) for the treatment of spinal muscular atrophy in pediatric and adult patients [news release]. Silver Spring, MD: FDA; Published December 23, 2016. Accessed May 18, 2020.

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