The SMA Researcher Meeting is the largest research meeting in the world specifically focused on SMA and seeks to create open communication of early, unpublished data to accelerate the pace of research.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 year, 530 researchers attended the meeting—a record number!
To highlight the most interesting new discoveries presented, we’ve posted a series of summaries from the 2018 Researcher Meeting. This update covers the highly anticipated closing session on SMA Therapies, where nine talks were given on drugs in preclinical or clinical development. This session was moderated by Katherine Klinger, PhD.
Effective Treatments for All Ages, Stages and Types of SMA
In December 2016, the approval of Spinraza marked the first-ever FDA approval of a treatment for SMA. Like Spinraza, many of the other programs in the drug pipeline work to address the loss of SMN protein by replacing SMN1 or by modulating SMN2, the low-functioning SMA “backup gene.” These are called “SMN-based” or “SMN-enhancing” approaches. There are also a number of systems, pathways and processes that are affected in SMA, and there may be additional ways to treat SMA in these other areas—collectively referred to as “non-SMN” approaches. These non-SMN approaches include drugs that work on the muscles and nerves. Research strongly suggests that a combination of SMN-enhancing and non-SMN approaches is the best route to treat all ages, stages, and types of SMA. During the SMA Therapy Development Session, nine talks were given on the most advanced of these approaches.
Summary of Session Talks
The session began with two talks focused on assessment of the experience of adults and children treated with Spinraza, developed by Biogen. The first talk, given by Bakri Elsheikh, MD, detailed the Ohio State University Wexner Medial Center experience in treating adults with SMA with Spinraza. Dr. Elsheikh described patient rationale for electing to undergo or not undergo treatment as well as a cervical spinal cord injection approach for patients with scoliosis and spinal fusion. Dr. Jacqueline Montes, DPT, gave the next talk regarding ambulatory function and fatigue in children with SMA treated with Spinraza. She explained that children with SMA who were ambulatory at the start of their Spinraza dosing where able to demonstrate improvements in ambulatory function, as determined by the 6-minute walk test, with increases in walking distances and decreases in fatigue.
The next two talks highlighted studies of the safety and efficacy of Spinraza. Dr. Michelle Farrar, MD, presented an interim analysis of the SHINE study assessing longer-term safety and efficacy of Spinraza in infantile-onset SMA. SHINE is an open-label extension study for infants and children who participated in the ENDEAR and CHERISH trials. Data showed improvements in motor function and event-free survival continued among patients who started treatment in ENDEAR and motor function improved among those who started treatment in SHINE. The next talk, given by Dr. Darryl De Vivo, MD, focused on the phase 2 NURTURE study. Data showed that Spinraza continued to be benefit infants who initiated treatment in a presymptomatic stage of SMA; all were alive, none required permanent ventilation, and most were attaining motor milestones inconsistent with SMN Type I and some inconsistent with SMA Type II. Spinraza was well tolerated and no new safety concerns were identified.
The next talk by Dr. John Day, MD, PhD, was an update on CY5021: a phase 2 clinical trial of Reldesemtiv, a fast-skeletal muscle troponin activator, for the treatment of SMA in development by Cytokinetics. Treatment with reldesemtiv showed potentially clinically beneficial effects in adolescent and adult patients with SMA as evidenced by dose-dependent increases vs. placebo in Six Minute Walk and Maximal Expiratory Pressure. More information about this data can be found here.
Dr. Richard Shell, MD, described improvements in respiratory and bulbar function in patients with SMA Type I in the Avexis phase one trial of AVXS-101. These improvements lead to fewer and less lengthy hospitalizations compared to the natural history of SMA. These reductions in hospitalizations are thought to improve both the child and caregiver’s quality of life.
The next three talks were about RG7916, an oral SMN2 splicing modulator developed by Genentech/Roche and PTC Therapeutics . Dr. Ksenija Gorni, MD, PhD, described that in SUNFISH Part 1, RG7916 treatment modulated SMN2 mRNA and increased SMN protein in a dose-dependent manner. The clinical benefit of the selected dose level is being assessed in SUNFISH Part 2, which is currently recruiting globally. Next was a presentation of updated interim clinical data from Part 1 of the FIREFISH study investigating Risdiplam (RG7916) in babies with Type 1 SMA. The data presented by Dr. Baranello demonstrated that RG7916 significantly increase SMN protein in infants with type I SMA. Furthermore, at Day 182, over 90% of the babies achieved a greater than 4-point increase in CHOP-INTEND score compared to baseline. More information about RG7916 can be found here. Concluding the session was a talk by Dr. Enrico Bertini about a long-term, open-label follow-up study of Olesoxime, developed by Roche, in patients with type 2 or non-ambulatory type 3 SMA who participated in a placebo-controlled trial. Data from this study showed the Olesoxime maintained motor function over 12 months in treated patients, but this was not sustained at 18 months. More information about Olesoxime can be found in our news section.
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.