What Is in the SMA Pipeline?


Small biotech companies such as Scholar Rock and Cytokinetics have treatments in late-stage trials for spinal muscular atrophy. Novartis and Biogen also have products in the pipeline.

Spinal muscular atrophy (SMA) is a rare disease that only a few specialists and affected families knew about till a few years ago. The estimates of its incidence range from four to 10 per 100,000 live births, which would work out to between 150 and 375 cases per year in the U.S.

SMA has become better known because the FDA has approved three therapies for it, starting with Biogen and Ionis’ Spinraza (nusinersen) in December 2016, followed by the approval of

Novartis’ Zolgensma (onasemnogene abeparvovec-xioi) three years later and then Roche’s Evrysdi (risdiplam), an oral treatment, in August 2020. The price tags of the approved SMA drug have garnered a great deal of attention. Zolgensma is a one-time treatment priced at $2.1 million. It is widely referred to as the most expensively priced drug ever sold.

Now a handful of other therapies for SMA are in development, perhaps adding more choice and competition in the treatment of the rare disease. Some of the SMA drug are also being considered and tested as treatments for other diseases, such as Huntington’s disease.

Scholar Rock’s apitegromab is a selective inhibitor of the activation of myostatin. Myostatin is expressed in skeletal muscle cells, and the absence of the gene is associated with an increase in muscle mass and strength.

In June, the Cambridge, Massachusetts, biotech company released data from a phase 2 clinical trial of apitegromab in conjunction with Spinraza in patients with later onset of SMA. In this trial of 31 patients, 74% showed clinical improvement of at least 1 or 2 points in the Hammersmith Functional Motor Scale Expanded (HFMSE), an examination that assesses the muscle tone, motor patterns, reflexes, visual and auditory attention and behavior in patients with SMA.

Some studies have shown that patients treated with Spinraza stabilized or only experienced a small increase in the HFSME score. When apitegromab is added to treatment, some patients experienced a five- or 10-point increase in this score.

A phase 3 trial will begin by the end of 2021 and is expected to evaluate apitegromab as an add-on to Spinraza or Evrysdi in patients with nonambulatory Type 2 and Type 3 SMA.

Reldesemtiv is another SMA therapy in the clinical development part of the pipeline. Developed by Cytokinetics, reldesemtiv slows the rate of calcium release in fast skeletal muscle fibers, which leads to an increase in muscle contraction. In February 2021, investigators published data from a small phase 2 study of reldesemtiv on eight outcome measures in SMA, including the 6-minute walk distance (how far can a person walk in six minutes) and maximum expiratory pressure (MEP). Cytokinetics, a Bay area biotech, has not released information about further trials for this therapy in SMA. The company is conducting a phase 3 trial of reldesemtiv in patients with amyotrophic lateral sclerosis (ALS).

Meanwhile, Novartis is conducting a phase 3 trial to test a different route of administration for Zolgensma. The trial had been on a clinical hold since 2019 but in August, the company announced that the hold had been lifted. Currently, Zolgensma is administered intravenously. This trial is assessing intrathecal administration — an injection into the spinal canal — for Zolgensma for patients between 2- and 18-years-old not previously treated for SMA.

Novartis is also developing branaplam, an oral therapy that might be used for both SMA and Huntington’s disease.Novartis executives have suggested they don’t see a big opportunity in SMA.

Biogen recently announced plans for a phase 3 trial that would test a higher dose of Spinraza in patients who have previously been treated with Evrysdi. The trial is designed to last about two and a half years. The goal is to enroll 135 volunteers. Biogen is also conducting a phase 1 trial of BIIB110, a muscle enhancing agent.

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