Nusinersen's Long-Term Success in SMA Lends Support to Higher Dose Trial


Further analysis of the SHINE trial suggest nusinersen is linked to 6-year maintained improvement in patients with SMA. Biogen has announced a new global trial of a 50 mg loading dose in a broader cohort.

Dr Basil Darras

Basil Darras, MD, director, Neuromuscular Center and Spinal Muscular Atrophy Program, Boston Childrens Hospital

Basil T. Darras, MD

New data from the SHINE trial, an open-label extension study of nusinersen (Spinraza, Biogen) for patients with spinal muscular atrophy (SMA) suggest that the antisense oligonucleotide is associated to improvements or stabilization in ≥1 measures of motor function for up to nearly 6 years of treatment, in contrast to the expected decline observed in natural history of the disease.1

“These findings are important in understanding the need for long-term treatment in individuals with SMA,” said lead study author Basil T. Darras, MD, director, Neuromuscular Center and Spinal Muscular Atrophy Program, Boston Children’s Hospital, and professor of neurology, Harvard Medical School, in a statement. “These data reinforce the long-term safety and durability of SPINRAZA to improve or stabilize motor function in individuals with later-onset SMA.”

SHINE (NCT02594124) included 24 patients with SMA type 2 (n = 10) and type 3 (n = 14) who transitioned from the CS2/CS12 studies. Measures of motor function in the SHINE study analysis consisted of the Hammersmith Functional Motor Scale—Expanded (HFMSE), the Upper Limb Module (ULM), and the 6-Minute Walk Test (6MWT). Notably, there were no discontinuations due to adverse events (AEs), and no additional safety concerns were identified during almost 6 years of follow-up.

New data demonstrating the safety and efficacy of treatment with the Biogen therapy in those with later-onset SMA will be featured in a podium presentation at the 13th Congress of the European Pediatric Neurology Society in Athens, Greece, from September 17-21, 2019.

Additionally, Biogen announced that it will initiate a new global trial of a higher dose of nusinersen across a broader population of patients with SMA. Dubbed DEVOTE (NCT04089566), the trial will feature a 3-part assessment—a randomized phase, an open-label phase, and an open-label dose transition phase.

The phase 2/3 DEVOTE study will be conducted at 50 sites worldwide and is aiming to enroll 126 individuals with SMA. It will explore 2 loading doses of 50 mg nusinersen, administered 15 days apart, followed by a maintenance dose of 28 mg every 4 months (equally 4 quarterly loading doses with 12 mg maintenance doses).

“Spinraza has fundamentally changed the natural history of SMA,” said Alfred Sandrock, Jr., MD, PhD, executive vice president, and chief medical officer, Biogen. “Antisense oligonucleotides directly intervene at the origin of disease providing a transformative therapeutic option. Spinraza’s highly targeted approach and well-characterized safety profile allows us to continue exploring ways to potentially address the remaining medical needs in the SMA community.”

In May, data from the CS2/CS12 studies were published, suggesting that of the 11 patients with SMA type 2 and 17 with SMA type 3, all measures of motor function improved by day 1150. HFMSE scores improved by 10.8 points and 1.8 points for type 2 and type 3 patients, respectively, while ULM scores improved by 4 points for the type 2 patients and 6MWT distance improved by 92 m in type 3 patients.2

Additionally, results from additional analysis of the NURTURE study, presented at the Cure SMA Annual SMA Conference and the 5th Congress of the European Academy of Neurology suggested nusinersen shows prolonged efficacy and safety in presymptomatic pediatric patients with SMA after 45 months. The findings ultimately showed that 100% of the infants treated with nusinersen were able to sit without support while 88% were able to walk independently—milestones which are not documented in the natural history of SMA.3


1. Biogen Advances Spinal Muscular Atrophy (SMA) Clinical Research with New Study Evaluating a Higher Dose of SPINRAZA® (nusinersen) and Additional Data in a Broad Range of Patients [press release]. Cambridge, MA: Biogen; Published September 18, 2019. Accessed September 18, 2019.

2. Darras BT, Chiriboga CA, Iannaccone ST, et al. Nusinersen in later-onset spinal muscular atrophy: Long-term results from the phase 1/2 studies. Neurology. 2019;92(21). doi: 10.1212/WNL.0000000000007527.

3. Biogen Announces New Data Further Establishing SPINRAZA® (nusinersen) as a Foundation of Care in Spinal Muscular Atrophy for a Broad Range of Patients [press release]. Cambridge, MA: Biogen; Published July 1, 2019. Accessed September 18, 2019.

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