AAN 2017; Spinraza Data for SMA Continues to Impress

by Jim Radke | April 26, 2017 | Rare Disease Report

One of the best Christmas presents ever given was last December 23rd when the FDA approved Spinraza (nusinersen) for the treatment of spinal muscular atrophy (SMA) based on interim analysis of a phase 3 study.

For the approval, the FDA looked at data from 82 of the 122 infants enrolled in the study and that was enough to convince them that the drug was effective. This week at the AAN Annual Meeting, results from all of the children in that study – the ENDEAR study — were presented and continued to show the remarkable effects this drug can have on this very vulnerable population.

Spinraza (nusinersen) in Early-Onset SMA

ENDEAR was a phase 3, randomized, double-blind, sham-procedure controlled 13-month study in which infants (< 7 months of age) with SMA were given intrathecal nusinersen (12-mg scaled equivalent dose), or sham-procedure. Primary endpoints included proportion of modified section 2 Hammersmith Infant Neurological Examination (HINE) motor milestone responders (more categories improving [≥2-point increase or maximal score in kicking ability, or ≥1-point increase in head control, rolling, sitting, crawling, standing, or walking] than worsening) and event-free survival (time to death or permanent ventilation).

At the end of the study, there was a significantly greater proportion of nusinersen-treated motor milestone responders versus sham-control (51% versus 0%; P <.0001) demonstrating continued improvement over the previous interim analysis that led to the FDA approval (41% versus 0%; P<0.0001), and significantly greater nusinersen treatment benefit in event-free survival (hazard ratio=0.530; P= .0046).

Nusinersen demonstrated a favorable safety profile and the study confirmed that the FDA approved drug is an effective treatment option for these infants.

Spinraza (nusinersen) in Later-Onset SMA

In addition to the ENDEAR study, the drug was tested in a phase 3 study involving children, aged 2-12 years of age with later-onset SMA. The CHERISH study is a phase 3, global, multicenter, randomized, double-blind, sham-procedure controlled study in which patients were given Nusinersen [ 4 intrathecal injections (totaling 12mg non-scaled)] and a sham procedure. Patients were monitored over 15 months, with a primary endpoint of change in Hammersmith Functional Motor Scale–Expanded (HFMSE) score at month 15.

Eugenio Mercuri, MD, of Catholic University and Centro Clinico Nemo in Rome presented findings from the CHERISH trial during the Emerging Science session at the AAN meeting.

So far, the study has shown that the efficacy trends of nusinersun in the later-onset SMA children are similar to that observed in early-onset SMA children—namely that the drug is effective. In the data, available, Dr. Mercuri noted that in more than 57% of the treated patients, HFMSE scores improved by 3 or more points at month 15, compared to about 20% of the controls. The trial reported a “favorable safety profile” with no withdrawals due to adverse events.

What is Spinal Muscular Atrophy?

SMA is a genetic condition that leads to a deficiency in the spinal motor neuron (SMN) protein as a result of mutations of the survival motor neuron 1 (SMN1) gene. The severity of SMA correlates with the amount of SMN protein. Generally, the muscles most affected are those near the shoulders, hips, thighs and upper back. Muscles used for breathing and swallowing may also be affected. Infants with Type I SMA produce very little SMN protein and have a life expectancy of less than two years. Children with Type II have greater amounts of SMN protein but still have a shortened lifespan and are never able to stand independently. Children with Type III have a normal lifespan but accumulate life-long physical disabilities as they grow.

Nusinersen is an antisense oligonucleotide (ASO) that is designed to alter the splicing of pre-mRNA from the SMN2 gene in order to increase production of fully functional SMN protein.  Nusinersen is being investigated in Type I, II, and III SMA population.


Kuntz N, Farwell W, Zhong ZJ, et al. Nusinersen in Infants Diagnosed with Spinal Muscular Atrophy (SMA): Study Design and Initial Interim Efficacy and Safety Findings from the Phase 3 International ENDEAR Study. Presented at the AAN 2017 Annual Meeting; Boston, MA; April 22-28, 2017. Abstract 002.

Schneider E, Mignon L, Su J, et al. Nusinersen in Symptomatic Children with Later-onset Spinal Muscular Atrophy (SMA): Design of the Phase 3 CHERISH Study. Presented at the AAN 2017 Annual Meeting; Boston, MA; April 22-28, 2017. Abstract 184.

Mercuri E, Finkel R, Kirschner J, et al.  Efficacy and safety of nusinersen in children with later-onset spinal muscular atrophy (SMA): interim results of the phase 3 CHERISH study. Presented at the AAN 2017 Annual Meeting; Boston, MA; April 22-28, 2017.

TRNDS 2017

University of Rochester
Saunders Research Building
Helen Wood Hall Auditorium
255 Crittenden Blvd
Rochester, NY 14642

Date: Friday, May 12, 2017
Time: 7:30am – 3:45pm

TRNDS Speakers

Plan Your Stay

Hilton Garden Inn
Medical Center

30 Celebration Drive
Rochester, NY 14620

Phone: 585-424-4404


  • New Grants will Accelerate Clinical Trials in Rare Neurological Disorders
  • Neurogene Offers Access to Genetic Testing for Lysosomal Storage Disease
  • NIH launches 5-year, $10 million study on acute flaccid myelitis
  • Study refines ALS risk among first-degree relatives of patients with disease
  • NCATS Director Warns of 'Poorly Understood Public Health Implications of Rare Diseases'
  • Speeding Up Drug Discovery for Brain Diseases
  • NIH-Funded Project Aims to Build a ‘Google’ for Biomedical Data
  • Rare Disease Groups Seek Public Support to Renew Newborn Screening Act in Senate
  • Jsyne Gershkowitz, Amicus Therapeutics, TRNDS 2019
    (Podcast) Get to know Jayne Gershkowitz, Chief Patient Advocate at Amicus Therapeutics
  • PJ Brooks, NCATS, NIH, TRNDS
    Meet TRNDS 2019 Speaker PJ Brooks
  • Rare Pediatric Disease PRVs: FDA Updates Guidance
  • Batten Disease Study
    Neurogene Opens Natural History Study of CLN7, CLN5 Diseases at UT Southwestern
  • C-Path and NORD Collaborate to Launch Rare Disease Data Platform
  • TRNDS 2019 speaker Tauna Batiste, BDSRA
    Meet TRNDS Speaker Tauna Batiste
  • HD Patients Prefer Less Invasive, No-Placebo Gene Therapy Trials
  • Evidation & Eli Lilly Study Uses Apple Devices, Apps to Predict Cognitive Impairment
  • 'Dr. Google' Helps Some Patients Diagnose a Rare Disease
  • Antisense Drugs for HD, ALS & Prion Could Meet the Need for Brain Treatments
  • Ultragenyx Partners with GeneTx to Advance Treatment for Angelman Syndrome
  • Netflix's Medical Investigation Docuseries 'Diagnosis'
  • NIH All of Us Project Tops 270,000 Sign-ups
  • FDA Cancer Office Taps Syapse for Real-world Evidence Development