Nusinersen Proven to be Effective in SMA


Nusinersen treatment proven to be efficient in spinal muscular atrophy (SMA).

Yesterday, at the 70th Annual American Academy of Neurology (AAN) Meeting, Biogen presented new data regarding its product nusinersen (SPINRAZA) for the treatment of populations with both infantile- and later-onset spinal muscular atrophy (SMA), including improvement in motor function and increased survival for the most severely affected.

The data come from the SHINE open-label extension (OLE) study and an analysis of the drug’s effects on mobility and fatigability in later-onset participants from the CS2/CS12 studies.2

Nusinersen is an antisense oligonucleotide (ASO). It is engineered to treat SMA caused by mutations or deletions in the SMN1 gene located in chromosome 5q that leads to SMN protein deficiency. Nusinersen alters the splicing of SMN2 pre-mRNA in order to increase production of full-length SMN protein; it has the potential to increase the amount of full-length SMN proteins in individuals with SMA.1

SMA is the result of the loss of motor neurons in the spinal cord and lower brain stem, which can lead to severe and progressive muscular atrophy and weakness. Paralysis and difficulty performing basic life functions, such as breathing and swallowing, characterize the most severe types of SMA.

The SHINE study was designed to evaluate patients (n=89) with infantile-onset SMA (most likely to develop Type 1) who transitioned from the Phase 3 ENDEAR study and either initiated nusinersen treatment in ENDEAR (which was another Phase 3 study that evaluated the efficacy and safety of nusinersen in patients with SMA) and continued treatment through SHINE (n=65) or transitioned from the sham-control arm in ENDEAR to active treatment with nusinersen in SHINE (n=24).3

Interim results from the ENDEAR study showed participants who initiated nusinersen and continued in the SHINE study encountered improvements in HINE-2 motor milestones and general motor function as measured by CHOP INTEND.

Seventy-three weeks was the median time to death or permanent ventilation for participants who initiated nusinersen in ENDEAR. With the ENDEAR study alone, 22.6 weeks was the median time to death or permanent ventilation. For the majority of participants who received sham in ENDEAR and who were alive and did not require permanent ventilation, they remained event-free after receiving nusinersen in SHINE for a median time of 9.2 months.

In an additional analysis led by researchers at Columbia University Medical Center with support from Biogen, data from CS2 and CS12 (two multicenter, open-label clinical trials) were evaluated to assess change in participants’ performance during the Six-Minute Walk Test (6MWT) and measures of fatigue. Walking ability and fatigability of ambulatory participants (n=14) ages 2 to 15 years with SMA Type 2 (n=1) or Type 3 (n=13), at study enrollment, were assessed. Subsequent to nusinersen treatment, walking distance increased (a median increase of 98 meters) in participants while their fatigue level remained stable or decreased (a median decrease of 3.8%) simultaneously over approximately 3 years. The baseline median distance walked was 250.5 meters and baseline median fatigue level was 14.8 % in participants.

Jacqueline Montes, PT, EdD, NCS., Assistant Professor, lead study author, Columbia University Irving Medical Center, New York, commented on the drug’s shown efficacy. “With SPINRAZA [nusinersen] treatment, not only were participants able to walk longer distances but they experienced a stabilization or decrease in fatigue while doing so — both of which are meaningful, real-world benefits for individuals with SMA. Furthermore, the analysis illustrates that SPINRAZA’s [nusinersen’s] benefits continue to grow over time for Type 2 and 3 SMA populations.”

For more on clinical trials in the rare disease community, follow Rare Disease Report on Facebook and Twitter.


  1. New SPINRAZA (nusinersen) Data Unveiled at AAN Annual Meeting Show Continued Improvement in Motor Function for Broad Age Range and Survival Benefit for Infants. Accessed April 24, 2018.
  2. Expanded Access Program (EAP) for Nusinersen in Participants With Infantile-onset (Consistent With Type 1) Spinal Muscular Atrophy (SMA). Accessed April 24, 2018.
  3. A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy (SMA). Accessed April 24, 2018.
Related Videos
How Gene and Cell Therapy Is Developing in Dermatology
Joyce Teng, MD, PhD, discusses how therapeutic advances in fields like epidermolysis bullosa should progress treatment discourse in other rare dermatoses.
The Prospect of Pz-cel in RDEB Treatment, with Peter Marinkovich, MD
Comparing New Therapies for Dystrophic Epidermolysis Bullosa
Reviewing 2023 with FDA Commissioner Robert M. Califf, MD
Dunia Hatabah, MD | Image Credit: HCPLive
Ricky Safer: What Clinicians Need to Know About PSC
Ryan T. Fischer, MD: Long-Term Odevixibat Benefit for Alagille Syndrome
Saeed Mohammad, MD: IBAT Inhibitors for Cholestatic Disease
Mercedes Martinez, MD: Treatment Strategies for Autoimmune Hepatitis
© 2024 MJH Life Sciences

All rights reserved.