Letter to provincial governments regarding SMA therapy outcome measures

The landscape of disease-modifying therapies for spinal muscular atrophy (SMA) in Canada is rapidly changing. Nusinursen (Spinraza), an antisense oligonucleotide, is currently approved for children and, more recently, adults. Two others are currently under review by Health Canada: onasemnogene abeparvovec-xioi (Zolgensma), a gene replacement for children under age 2, and RG 7916 (Risdiplam), a splice modifier.

With these new therapies coming on the scene, it is important to monitor their effectiveness and to collect evidence to help determine which therapy should be chosen for any given patient. However, the current provincial government monitoring requirements are too frequent and there is significant variability between the provinces.

A group of Canadian neuromuscular disease specialists, most of whom are involved in NMD4C, have written a letter to the provincial governments outlining their concerns and recommending an alternative timeline for outcome measurements in patients receiving the therapies.

 

The full letter is not yet available; it will be published in the Canadian Journal of Neurological Sciences HERE. In the meantime, you can read our summary below.

 

Written by: Victoria Hodgkinson (NMD4C collaborator) and Kerri Schellenberg (NMD4C member)

Reviewed and approved by: Kristine Chapman, Aaron Izenberg (NMD4C member), Hanns Lochmüller (NMD4C lead investigator), Colleen O’Connell, Erin K. O’Ferrall, Maryam Oskoui (NMD4C investigator), Gerald Pfeffer (NMD4C member), Stephanie Plamondon (NMD4C member), Xavier Rodrigue (NMD4C member), Christen Shoesmith, Jodi Warman Chardon (NMD4C steering committee member), Bernard Brais (NMD4C investigator), and Lawrence Korngut (NMD4C investigator)

 

Frequency of monitoring

The natural history of SMA is a slowly progressive functional decline. Patients’ function decreases by a statistically significant amount in the matter of years, not months. As such, any decline in outcome measure scores in the span of months is more likely to be due to to inter- or intra-examiner variability (i.e., the normal statistical range of error) or variability in patient effort (i.e., SMA patients have “off days” and “good days” just like anyone else) than due to a true effect of the therapy. This potential artificial decline in outcome measure scores could lead to inappropriate termination of therapy provision.

Human resource strain and patient burden

Motor outcome assessments are time-consuming and personnel-intensive, requiring significant time from physical therapists and/or respiratory therapists with specialized training. As such, there are ethical concerns around mandating that these scarce resources be utilized to provide frequent monitoring for largely stable patients for whom such frequent monitoring is not clinically relevant or evidence-based. Frequent clinic visits can also be fatiguing, time-consuming, and costly for patients.

Collection of real-world evidence and proposition for appropriate monitoring

The Canadian Neuromuscular Disease Registry (CNDR) has a clear plan to assess the effectiveness of novel therapies in a broad population. The CNDR’s SMA working group of expert investigators is currently evaluating specific outcome assessments by way of a Delphi model to determine best practices (manuscript in preparation). They recently agreed that the best timing for outcome measurements is: at baseline, 6 months later, then annually thereafter. This timing is appropriate for clinical monitoring, congruent with available evidence in treated adults, and does not put undue burden on provincial and clinical resources or on patients and families.

The shared goal of the health care system is to provide a standard of care which is acceptable for patients, maintains appropriate resource allocation for all populations, and is feasible for the clinics. The proposed monitoring system achieves these goals.

writing-1149962_1920

Read next...

poster congratulating King's Medal Recipient

King’s Medal Awarded to Canadian Neuromuscular Clinicans and Researchers

Several NMD4C investigators and collaborators from the Canadian neuromuscular community have been awarded a King Charles III’s Coronation Medal in recognition of their outstanding contributions and service.

Announcement poster reading: New home online for NMD4C community of practice

New Home on NMD4C Website for Community of Practice

Check out the new home for the NMD4C community of practice (CoP), now live on the NMD4C website!

announcement text reading: New NMD4C Collaborative Research Training Awards, launching May 7 2025

New NMD4C Collaborative Research Training Awards Launching May 2025

The NMD4C is excited to announce a new program for neuromuscular research trainees that will support collaboration opportunities between Canadian research labs.

Neuromuscular research funding opportunities

Neuromuscular Research Grant Competitions from Defeat Duchenne Canada and Myotonic Dystrophy Foundation You Can Apply For Today!

Applications are open for Defeat Duchenne Canada’s research grant cycle, and Myotonic Dystrophy Canada’s fellowship and scholar grant programs.

NMD4C Reaches 800-Member Milestone!

NMD4C Reaches 800 Member Milestone

We are thrilled to announce that the NMD4C has reached the milestone of 800 members! This incredible number shows the strength and engagement of the diverse neuromuscular community in Canada.

Text reading NMD4C joins bluesky - We're now active on Bluesky! We invite you to follow us at @nmd4c.ca to stay updated on news from our Canadian neuromuscular network. NMD4C and bluesky logo, with an image of the NMD4C bluesky feed.

You Can Now Find NMD4C on Bluesky

We’re moving to Bluesky! The NMD4C will now share updates on Bluesky instead of X. Please consider following us at @nmd4c.ca to stay connected!