The annual SMA Researcher Meeting is the largest research meeting in the world specifically focused on SMA. This year, we had a record setting 735 attendees join together in Anaheim, CA. The goal of the meeting is to create open communication of early, unpublished data, accelerating the pace of research. The meeting also furthers research by building collaborations—including cross-disciplinary dialogue, partnerships, integration of new researchers and drug companies, and educational opportunities for junior researchers.

This is the fourth in a series of summaries from our 2019 researcher meeting, highlighting the most interesting new discoveries presented there. This update covers the highly anticipated closing session on SMA Therapies, where ten talks were given on drugs in pre-clinical or clinical development. This session was moderated by Dr. Stephen Kolb (Ohio State University).

The session began with three talks on the AveXis gene-replacement therapy trials. The first talk, given by Dr. Kevin Strauss (Clinic for Special Children), proved an update on the SPR1NT trial in presymptomatic infants. SPR1NT is an open label phase 3 study that enrolled infants 6 weeks of age or younger for a one-time intravenous AVXS-101 infusion. Preliminary data from SPR1NT show rapid motor function improvements in presymptomatic SMA patients as assessed by CHOP INTEND. The next talk, given by Dr. John Day (Stanford University), provided an update on STR1VE, a phase 3 study of intravenous AVXS-101 in patients with 2 copies of SMN2 less than 6 months of age. Data from this study show rapid motor function improvements in treated patients as assessed by CHOP INTEND with 18/21 patients needing no non-invasive ventilation support. Dr. Richard Finkel (Nemours Children’s Hospital) spoke about the STRONG trial, an open-label study of patient with SMA type 2 (3 copies of SMN2) who could sit but not stand or walk at ages 6-60 months receiving a one-time intrathecal dose of AVXS-101. Results from the STRONG data thus far show that intrathecal delivery of AVXS-101 in patients of this age range is feasible, well tolerated, and safe at the doses described in patients treated at the time of this presentation. For more information about the AveXis trials, please see here.

The next two talks highlighted studies of the safety and efficacy of Spinraza. Dr. Julie Parsons (Children’s Hospital of Colorado) presented interim results of the NURTURE study assessing the safety and efficacy of Spinraza in infants treated prior to symptom onset with 2 or 3 copies of SMN. There were no new safety concerns identified and there was continued benefit to infants who initiated Spinraza prior to symptom onset, emphasizing the value of early treatment and newborn screening. Next Dr. Basil Darras (Boston Children’s Hospital) gave an update on SHINE, an open-label extension for participants in previous Nusinersen studies. Data showed improvements in motor function among patients who started treatment in CHERISH and there were no new safety concerns. For more information about these trials, please see here.

Dr. Giovanni Baranello (Dubowitz Neuromuscular Centre, London) provided 1- year results of FIREFISH Part 1, an ongoing open-label study of Risdiplam in infants aged 1-7 months at enrollment with 2 copies of SMN2. FIREFISH is a two-part study of Risdiplam: part 1 assesses the safety and tolerability of different doses and confirmatory part 2 assesses the safety and efficacy of Risdiplam. To date, no drug-related safety findings have led to withdrawal of any infants from the study. Despite not being designed to detect efficacy, Risdiplam improved motor function infants in part 1. The next talk, given by Dr. Basil Darras (Boston Children’s Hospital), provided an update on survival, ventilation, and swallowing ability in FIREFISH part 1. No infant has lost the ability to swallow during the study, and no infant has required tracheostomy or permanent ventilation. Event-free survival rates were improved in infants receiving Risdiplam compared with infants of the same age in natural history studies. Dr. Laurent Servais (Institute of Myology, Paris) spoke about SUNFISH Part 1 which was designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and provide exploratory efficacy data in patients with Type 2 or 3 SMA, aged 2-25 years receiving Risdiplam. To date, no drug-related safety findings have led to withdrawal and Risdiplam had led to sustained increases in SMN protein.  Despite part 1 not being designed to test efficacy, patients on Risdiplam showed improvement over 12 months in motor function measures when compared with natural history data. For more information, please see here.

The next speaker, Dr. Ying Chyung (Scholar Rock) presented interim results from the phase 1 study of SRK-015, an antibody that inhibits myostatin activation in muscle. Phase 1 tested the safety of SRK-015 in healthy volunteers. To date, no safety signals for SRK-015 have been observed and SRK-015 displays confirmed target engagement. The data from phase 1 support investigating safety and efficacy of SRK-015 in the phase 2 trial in patients with SMA, TOPAZ. For more information, please see here.

The final speaker of the session, Dr. Marloes Stam, discussed the SPACE trial, a phase 2, placebo-controlled cross-over trial to assess efficacy of Pyridostigmine in patients with SMA types 2,3, and 4. Data from the trial show that Pyridostigmine reduced fatigability in patients, shown by decreased dropout in endurance tests and that there were no serious adverse effects.

Advancing Our Therapy Development Goals

The drug programs described in this session include both SMN-enhancing and non-SMN approaches. As the drug programs continue to move forward and as we continue to work through issues surrounding access to approved therapies, we also remain focused on continued growth of the SMA drug pipeline to allow for maximally effective treatment options for SMA patients of all types, ages, and stages.

2019 Researcher Meeting Summaries

Clinical Research Studies for SMA

Basic Research Podium Presentations

Special Session on Spinal and Neuromuscular Circuitry: Exploring Defects in SMA and Potential Therapeutic Targets