Breakthrough Therapies for Spinal Muscular Atrophy: A New Era of Treatment

Spinal muscular atrophy (SMA) treatment has undergone a revolutionary transformation in recent years, with multiple pharmaceutical companies making significant strides in developing innovative therapies. This article explores the latest advancements in SMA treatment, highlighting promising candidates in various stages of clinical development.

Novartis' Intrathecal Zolgensma Shows Promise for Older Patients

Novartis has announced positive safety and efficacy results for OAV101 IT, an intrathecal injection formulation of its gene therapy Zolgensma. The Phase III STEER study demonstrated that OAV101 IT improves motor muscular ability in patients aged 2-17 years, potentially expanding the treatment's reach beyond its current FDA approval for intravenous delivery in children under 2 years old.

The study showed a 2.39-point improvement on the Hammersmith Functional Motor Scale Expanded (HFMSE) for patients treated with OAV101 IT, compared to a 0.51-point improvement in the control arm. Norman Putzki, global development head of neuroscience and gene therapy at Novartis, described the motor gains as "clinically meaningful" and "really exciting."

Novartis plans to file for regulatory approval of OAV101 IT in the first half of 2025, potentially offering a new treatment option for older SMA patients.

Muscle-Targeting Therapies: A New Frontier in SMA Treatment

While many SMA treatments focus on increasing the production of the survival motor neuron (SMN) protein, a new class of therapies is emerging that directly targets muscle function.

Scholar Rock's apitegromab, a myostatin inhibitor, has shown promising results in its Phase III SAPPHIRE trial. Patients aged 2 to 12 years receiving apitegromab experienced clinically meaningful benefits in motor function, with 30% of treated patients seeing at least a 3-point improvement in HFMSE compared to 12.5% in the placebo group. Seth Perlman, a neurologist at Seattle Children's Hospital, suggests that apitegromab could be an effective "add-on" to other therapies, especially for people with SMA who may have already developed muscular weakness.

NMD Pharma is testing NMD670, a small molecule inhibitor of skeletal muscle-specific chloride ion channel 1 (CIC01), in a Phase II trial for SMA. The study, which began in late 2023, is evaluating changes in a 6-minute walk test in ambulatory adults aged 18 to 75. While earlier in development than other candidates, NMD670 has shown promise in early-stage trials for other neuromuscular disorders, such as myasthenia gravis.

Biogen's Dual Approach: Higher-Dose Spinraza and New Antisense Oligonucleotide

Biogen is pursuing two strategies to enhance SMA treatment. The FDA has accepted the company's supplemental new drug application for a higher dose of Spinraza, an antisense oligonucleotide that alters the splicing of the SMN2 gene. The proposed higher-dose regimen comprises a loading regimen of two 50-mg doses 14 days apart, followed by a 28-mg maintenance regimen every four months.

Additionally, Biogen is developing BIIB115, another antisense oligonucleotide licensed from Ionis Pharmaceuticals. BIIB115 is currently in a Phase I trial to assess safety and pharmacokinetic effects in healthy adult male volunteers and pediatric SMA patients previously treated with Zolgensma. The study is expected to conclude in November 2026.

These developments in SMA treatment represent a significant shift in the therapeutic landscape. Dr. Thomas Crawford, co-director of the Muscular Dystrophy Association Clinic at Johns Hopkins Medicine, noted that before 2016, many patients with the most severe form of SMA did not survive past two years of age without respiratory support. Today, the outlook for SMA patients has dramatically improved, with multiple treatment options available and more in development.

As these new therapies progress through clinical trials and regulatory processes, the pharmaceutical industry continues to push the boundaries of SMA treatment, offering hope for improved outcomes and quality of life for patients affected by this rare neuromuscular disease.