6 Therapies on the Horizon for Spinal Muscular Atrophy
The final decade has basically modified how clinicians deal with spinal muscular atrophy. In 2016, Biogen’s Spinraza grew to become the FDA-approved remedy for SMA, providing new hope for sufferers with the uncommon, neuromuscular illness. Since then, two extra medicines—Novartis’ gene remedy Zolgensma and Roche’s SMN2 splicing modifier Evrysdi—have hit the market, and plenty of extra are in varied phases of growth.
Earlier than 2016, with out remedy, many sufferers with probably the most extreme type of SMA didn’t survive previous two years of age with out respiratory assist, in keeping with Biogen.
“The panorama of SMA has modified drastically for the higher,” Seth Perlman, a neurologist at Seattle Kids’s Hospital, advised BioSpace. “It’s a fully totally different world. We’re not anticipating to see kids die earlier than age two.”
SMA is brought on by a dysfunction within the survival motor neuron (SMN) protein, usually on account of a mutation within the SMN1 gene. The SMN protein is important for cell survival. It repairs DNA, manages mobile stress and preserves general neuromuscular well being. With out it, motor neurons waste away. Most investigational medicine search to spice up the quantity of practical protein or ship a practical copy of the SMN1 gene, however latest improvements on this area additionally goal muscle mass instantly.
Right here, BioSpace seems at six SMA therapies and novel formulations to look at in 2025 and past.
Novartis’ IT Zolgensma (OAV101 IT)
Final week, Novartis introduced constructive security and efficacy readouts for OAV101 IT, an investigational intrathecal injection of its landmark gene remedy, Zolgensma (onasemnogene abeparvovec). The one gene remedy for SMA on the U.S. market, Zolgensma is presently FDA-approved for intravenous supply in kids beneath 2 years of age.
Information from the Part III STEER research, introduced March 19 on the Muscular Dystrophy Affiliation’s Medical & Scientific Convention in Dallas, confirmed that remedy with OAV101 IT improves motor muscular capacity in sufferers 2–17 years of age, doubtlessly increasing the cohort of sufferers who can profit from this remedy. OAV101 IT differs from the accepted formulation of Zolgensma in that it’s delivered instantly into the spinal fluid, which Norman Putzki, world growth head of neuroscience and gene remedy at Novartis, mentioned permits for safer supply of the drug within the greater doses required to successfully deal with older sufferers.
In STEER, OAV101 IT elicited a 2.39-point enchancment on the Hammersmith Useful Motor Scale Expanded (HFMSE)—a gold normal SMA evaluation software, in keeping with Novartis’ press launch—in comparison with 0.51 factors within the management arm. “We’ve seen motor positive aspects which might be clinically significant,” Putzki advised BioSpace. “It’s actually thrilling.”
Novartis plans to file for approval of OAV101 IT with regulators within the first half of 2025.
Scholar Rock’s Apitegromab
Scholar Rock’s apitegromab, a myostatin inhibitor, sailed by means of Part III testing with flying colours.
Within the Part III SAPPHIRE trial, reported by Scholar Rock in October 2024, sufferers aged 2 to 12 years receiving apitegromab skilled clinically significant advantages in motor perform, with the remedy group seeing a minimum of a 1.8-point enchancment on the HFMSE in comparison with placebo. As well as, 30% of apitegromab-treated sufferers noticed a minimum of a 3-point enchancment in HFMSE in comparison with 12.5% within the placebo group.
In contrast to different medicine, apitegromab instantly targets muscle mass, selectively inhibiting the activation of myostatin. Perlman mentioned apitegromab could possibly be an efficient “add-on” to different therapies, particularly for folks with SMA who might have already developed muscular weak spot.
NMD Pharma’s NMD670
NMD Pharma is testing NMD670, a small molecule inhibitor of skeletal muscle-specific chloride ion channel 1 (CIC01), in a Part II trial for SMA. The primary affected person on this trial, which is evaluating adjustments in a 6-minute stroll check in ambulatory adults aged 18 to 75, dosed its first affected person in late 2023, in keeping with a firm press launch.
The research is estimated to wrap up in January 2026, in keeping with ClinicalTrials.gov.
Whereas earlier in growth than different medicine on this checklist, NMD670 has proven promise in early-stage trials of different neuromuscular issues. In a Part I medical trial, sufferers with myasthenia gravis skilled clinically significant enhancements within the Quantitative Myasthenia Gravis (QMG) rating—which assesses muscle management and performance—and electrophysiological assessments. The drug is assumed to reinforce muscle excitability, amplifying responses to motor instructions from the mind.
Biogen’s Greater Dose Spinraza and BIIB115
In January, the FDA accepted Biogen’s supplemental new drug software for the next dose of its Ionis-partnered Spinraza, an antisense oligonucleotide that alters the splicing of SMN2, a “backup” gene for SMN1 that produces a truncated model of the SMN protein. The drug, which is injected into the spinal fluid, allows the SMN2 gene to make full-length SMN protein, rising its manufacturing in sufferers with SMA.
The upper-dose routine, which includes a loading routine of two 50-mg doses 14 days aside, adopted by a 28-mg upkeep routine each 4 months, may “allow significant medical advantages whereas sustaining a security profile broadly in line with the accepted 12-mg routine,” Thomas Crawford, co-director of the Muscular Dystrophy Affiliation Clinic at Johns Hopkins Drugs, mentioned in Biogen’s acceptance announcement.
However Biogen isn’t resting on the success of Spinraza. In January 2022, the large biotech exercised an choice from Ionis for an unique world license for an additional antisense oligonucleotide, BIIB115, which in keeping with Ionis gives the potential for prolonged dosing intervals.
Biogen is presently testing BIIB115 in a Part I trial supposed to establish security and pharmacokinetic results in wholesome grownup male volunteers and pediatric SMA sufferers who had been beforehand handled with Zolgensma. The research is predicted to learn out in November 2026, in keeping with Clinicaltrials.gov.
Biohaven’s Taldefgrobep Alfa
Biohaven’s investigational myostatin and activin receptor blocker, taldefgrobep alfa, missed the mark in a latest Part III trial, however the Connecticut-based biotech hasn’t given up on the drug but. In Biohaven’s RESILIENT SMA research, taldefgrobep alfa failed to enhance motor perform in sufferers with SMA as in contrast with placebo, in keeping with a November 2024 press launch. Biohaven famous, nevertheless, that in Caucasian sufferers, the drug confirmed a statistically vital enchancment. Sufferers on this subset handled with taldefgrobep alfa confirmed a statistically vital 2.2-point enchancment within the Motor Perform Measurement-32 (MFM-32) scale at 48 weeks. Non-Caucasian sufferers, nevertheless, confirmed a higher-than-average response to the placebo, Biohaven mentioned.
The corporate struck an optimistic tone relating to the drug’s efficacy and plans “to have interaction the FDA relating to potential steps ahead” for the candidate.
Biohaven additionally found that remedy with taldefgrobep alfa resulted in a discount of physique fats and enhancements in lean muscle mass and bone density. Primarily based on these findings, the corporate said plans to launch a Part II trial in weight problems in This fall, 2024.
