Clinical Research and Drug Development Session Highlights from 2023 SMA Research & Clinical Care Meeting

1. Assessing Perceived Fatigability in Adolescents and Adults with SMA: Results from a Pilot Study

Rafael Rodriguez-Torres, DPT ~ Columbia University Irving Medical Center

Main Points:

• Although there are tools for measuring how much muscle fatigue is caused by specific activities, a scale for measuring whole-body, perceived fatigue felt by individuals with SMA has not been established.

• In this study, the researchers tested a patient-reported outcome measure for quantifying perceived fatigue in teens and adults with SMA.

2. Muscle Ultrasound in Children with SMA Treated with Early Mono- or Dual Therapy

Susan E. Matesanz, MD ~ University of Pennsylvania Perelman School of Medicine

Main Points:

• Biomarkers are needed to help SMA healthcare providers make informed decisions about how and when to offer treatment to patients.
• In children with SMA who had been treated by one or two disease modifying therapies, Dr. Matesanz’s group tested the effectiveness of a non-invasive tool called muscle ultrasound (MUS) in evaluating muscle health. Their findings suggest that MUS may be a useful biomarker for predicting SMA treatment outcomes.

3. Serum Neurofilament Levels and Maximum Ulnar CMAP in the Real-World Setting to Monitor Impact of Molecular Therapies on Clinical Outcomes in Infants with SMA Indicate a Potential Protective Effect of Nusinersen Dosing Prior to IV Onasemnogene Dosing in Vulnerable SMA Infants

Kathryn Swoboda, MD ~ Massachusetts General Hospital and Harvard Medical School

Main Points:

• In some individuals with SMA, treatment with more than one FDA-approved, disease-modifying drug may achieve the best health outcomes.
• By using compound muscle action potential (CMAP) and a protein called neurofilament (NF) as biomarkers, Dr. Swoboda and her colleagues found that treating some infants with nusinersen followed by onasemnogene abeparvovec may achieve better results than treating them with onasemnogene abeparvovec alone.

4. Preliminary Results from an Ongoing Pilot Clinical Trial Testing the Effects of Spinal Cord Stimulation on Motor Function in Humans with Type 3 SMA

Marco Capogrosso, PhD ~ University of Pittsburgh

Main Points:

• In SMA, motor neuron dysfunction may result in part from reduced excitatory input.
• Capogrosso’s research group used spinal cord stimulation (SCS) to increase excitatory input to affected motor neurons in people with Type 3 SMA. Their findings suggest that 4 weeks of SCS therapy may have improved motor neuron function.

5. Risdiplam Experience Following Onasemnogene Abeparvovec in Individuals with Spinal Muscular Atrophy: A Multicenter Case Series

Melissa D Svoboda, MD ~ The Children's Hospital of San Antonio/Baylor College of Medicine

Main Points:

• Individuals with SMA and their caregivers are becoming more interested in combination treatment, but information on combination treatment outcomes is limited.
• Svoboda and her fellow researchers combined and analyzed real-world data from six neuromuscular centers across the United States to identify trends in outcomes for children with SMA who are treated with onasemnogene abeparvovec followed by risdiplam.

6. Evaluation of Molecular Response to Risdiplam in SMA Patients through the Analysis of SMN2 Transcript Levels in Peripheral Blood

Emanuela Abiusi, MD ~ Università Cattolica del Sacro Cuore, Rome, Italy

Main Points:

• Risdiplam works by increasing levels of full length SMN2 RNA that is translated into functional SMN protein.
• In this study, Dr. Abiusi’s group measured levels of full length SMN2 RNA in the blood of adults with SMA who were treated with risdiplam. They studied how changes in SMN2 RNA levels related to clinical outcome measures in the adults whose blood was analyzed.

1. Interim Results from the Ongoing Respond Study Evaluating Nusinersen in Children with Spinal Muscular Atrophy Previously Treated with Onasemnogene Abeparvovec

Crystal Proud, MD ~ Children's Hospital of The King's Daughters, Norfolk, VA

Main Points:

• RESPOND is an open-label clinical trial designed to determine if treatment with nusinersen results in additional gains in health and function for children who have previously been treated with onasemnogene abeparvovec.
• Proud and her colleagues have enrolled into the RESPOND trial 38 children with SMA who are three years old or younger. RESPOND clinical trial enrollment is ongoing.
• For more information on these trial results, click here.

2. FIREFISH Parts 1 and 2: 4-Year Efficacy and Safety of Risdiplam in Type 1 Spinal Muscular Atrophy

Giovanni Baranello, MD ~ Great Ormond Street Hospital Biomedical Research Centre, London, UK

& Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

Main Points:

• Parts 1 and 2 of the FIREFISH clinical trial were continued in a three-year open-label extension phase to determine the long-term safety and efficacy of risdiplam when treating infants with SMA Type 1.
• Baranello’s group found that enrolled infants who were treated with risdiplam continued to maintain or improve motor skills for up to 3 years.
• Click here to learn more about these findings.

3. SUNFISH Parts 1 and 2: 4-Year Efficacy and Safety Data of Risdiplam in Types 2 and 3 Spinal Muscular Atrophy

John W. Day, MD, PhD ~ Stanford University

Main Points:

• Parts 1 and 2 of the SUNFISH clinical trial determined the safety and effectiveness of risdiplam in people who had SMA Type 2 or non-ambulatory SMA Type 3 and were between the ages of 2-25 years old. At the end of Part 2, participants could enroll in an open-label extension trial.
• Day and his colleagues determined that participants who received risdiplam in SUNFISH Part 2 experienced motor function increases that were sustained through the third year of treatment.

4. Effect of Apitegromab on Pedi-CAT and PROMIS-Fatigue Questionnaire at 36-Months in Patients with Type 2 and Non-ambulatory Type 3 Spinal Muscular Atrophy

Thomas O. Crawford, MD ~ Johns Hopkins Medical

Main Points:

• In the TOPAZ open-label extension study, participants with Type 2 and non-ambulatory Type 3 SMA received Apitegromab is a molecule that works by reducing the activity of a protein called myostatin that limits muscle growth.
• Crawford’s group found that when apitegromab treatment was given alongside nusinersen for 3 years, patients and caregivers participating in the TOPAZ extension study reported sustained improvements in function and fatigue.

5. Effect of Apitegromab on Motor Function at 36-Months in Patients

with Type 2 and Non-ambulatory Type 3 Spinal Muscular Atrophy

Thomas O. Crawford, MD ~ Johns Hopkins Medical

Main Points:

• In clinical trials for SMA drugs, several measurement scales can be used by clinicians to gather information about how well the treatment is working.
• Using three separate scales to measure changes in motor function and quality of life for TOPAZ extension study participants, Dr. Crawford and his colleagues determined that participants experienced sustained benefit from apitegromab treatment for the 3-year duration of the trial.
• For more information about this study, click here.