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Updates on nusinersen/Spinraza Trials at the World Muscle Society Meeting

15 November 2017

The 22nd International Annual Congress of the World Muscle Society (WMS) was held October 3rd-7th 2017 in Saint Malo, France. While SMA Support UK did not attend, Biogen have uploaded three posters to their repository that were presented at the meeting. The posters all outline recent findings from clinical trials of the clinically approved antisense oligonucleotide gene therapy for SMA, nusinersen. Below we provide summaries of the main findings.

Poster 1: Efficacy and Safety of Nusinersen in Children with Later-Onset SMA: End of Study Results from the Phase 3 CHERISH Study.

The CHERISH trial was the Phase 3 study of nusinersen conducted in parallel with the successful Phase 3 ENDEAR trial, which was halted in late 2016 due to a positive interim analysis, leading to the clinical approval of nusinersen for SMA. Like the ENDEAR trial, the CHERISH study was stopped in early 2017 due to a positive interim analysis, with participants being transitioned onto the open-label extension study called SHINE to receive nusinersen.

The CHERISH trial was a randomised, double-blind, sham-procedure controlled study, which was conducted with non-ambulatory patients with SMA Type 2 or 3, aged 2-12 years with disease onset greater than six months. This trial format means that patients were randomly allocated to either the placebo or treatment group, and that this was concealed from the patients and the people administering the treatment.

Patients receiving nusinersen were given four 12 mg doses of the drug injected directly into the spinal cord over a period of nine months. The effectiveness of nusinersen was measured by assessing muscle function at the start of the trial before treatment and then again at the end, using the Hammersmith Functional Motor Scale Expanded (HFMSE) score. This scale is specifically designed to assess the motor function of children with SMA.

The results presented in Poster 1 are from the CHERISH interim and end of study analyses. The interim analysis was performed when all patients had completed their six month assessment, and more than 38 children had completed the trial. Specified at the start of the trial, an interim analysis is performed before the end of a trial in order to see whether a drug is having a positive effect.

We have reported on some of the initial findings from the CHERISH trial previously (click here for more information), but the end of trial results have not yet been published in a scientific journal.

The findings reported at the WMS meeting (Poster 1) indicate that:

  1. Nusinersen continues to be safe and well-tolerated.
  2. Nusinersen treatment resulted in a significant improvement in motor function at the interim analysis; patients treated with nusinersen showed an average improvement of 4.0 points in the HFMSE score, while patients receiving the placebo displayed a decline of 1.9 points (difference of 5.9 points).
  3. A significant improvement in motor function was also determined in the end of the study analysis, with nusinersen-treated patients displaying a clinically significant improvement of 3.9 points compared to the 1.0 point decline in the placebo group.
  4. Patients in the CHERISH trial have now been moved to the open-label extension study called SHINE, specifically designed for infants and children who have previously participated in the ENDEAR and CHERISH trials.
  5. These results provide additional evidence to support the use of nusinersen as an effective treatment for SMA.

Download Poster 1


Poster 2: Safety and Efficacy of Nusinersen in Infants/Children with SMA: Part 1 of the Phase 2 EMBRACE Study.

EMBRACE is a Phase 2 trial of nusinersen that enrolled a small number of SMA patients that were ineligible for inclusion in the ENDEAR and CHERISH Phase 3 trials.

Like CHERISH, EMBRACE is a randomised, double-blind, sham-procedure controlled study over 14 months designed to test the safety of injections of nusinersen into the spinal cord. Some information on effectiveness can also be determined from the trial, although this was not its primary purpose.

The main findings from this presentation (Poster 2) are as follows:

  1. Nusinersen continues to be safe and well-tolerated.
  2. Upon termination of the ENDEAR trial due to positive interim results, part 1 of the EMBRACE trial was ended, and all patients (20 children) were transferred to the open-label part 2 of the trial.
  3. Before the initiation of EMBRACE part 2, a greater percentage of patients (79%) receiving nusinersen showed attainment of key motor milestones compared to the sham procedure-treated (29%).
  4. While both treatment groups required ventilator use, the nusinersen-treated patients showed smaller increases over the duration of the trial than patients receiving the placebo.
  5. There was no difference in weight gain between the two treatment groups.

Download poster 2


Poster 3: Nusinersen Demonstrates Greater Efficacy in Infants with Shorter Disease Duration: Final Results from the ENDEAR Study in Infants with SMA.

ENDEAR was the first Phase 3 trial of nusinersen conducted with young infants with SMA that was terminated in late 2016 due to positive interim results. The end of trial results from this study were very recently published in the New England Journal of Medicine. SMA Support UK will be providing an update on this scientific publication shortly.

In the meantime, the main findings from the final poster (Poster 3) are as follows:

  1. Nusinersen continues to be safe and well-tolerated.
  2. Compared to the placebo group, nusinersen treatment resulted in a greater percentage of infants with SMA attaining key motor milestones and improved event-free survival and overall survival.
  3. The positive effects of nusinersen were greater in SMA patients that were treated closer in time to the onset of disease, i.e. the earlier that nusinersen was administered, the better the therapeutic effect.

Download Poster 3

Further Information

CHERISH trial site

EMBRACE trial site

ENDEAR trial site

NURTURE trial site

SHINE trial site