RARE Daily

Scholar Rock Reports Positive Topline Results from Therapy for SMA Types 2 and 3

April 6, 2021

Rare Daily Staff

Scholar Rock reported positive top-line data from the TOPAZ phase 2 clinical trial evaluating its experimental therapy apitegromab in patients with type 2 and type 3 spinal muscular atrophy, a rare neuromuscular condition.

Spinal muscular atrophy (SMA) is a rare, and often fatal, genetic disorder that typically manifests in young children. An estimated 30,000 to 35,000 patients are afflicted with SMA in the United States and Europe. It is characterized by the loss of motor neurons, atrophy of the voluntary muscles of the limbs and trunk, and progressive muscle weakness. The underlying pathology of SMA is caused by insufficient production of the SMN (survival of motor neuron) protein, essential for the survival of motor neurons, and is encoded by two genes, SMN1 and SMN2. While there has been progress in the development of therapeutics that address the underlying SMA genetic defect, there continues to be a high unmet need for therapeutics that directly address muscle atrophy.

Apitegromab (SRK-015) is a selective inhibitor of the activation of latent myostatin and is an investigational product candidate for the treatment of patients with spinal muscular atrophy (SMA). Myostatin, a member of the TGFβ superfamily of growth factors, is expressed primarily by skeletal muscle cells, and the absence of its gene is associated with an increase in muscle mass and strength in multiple animal species. Scholar Rock believes the inhibition of the activation of latent myostatin with apitegromab may promote a clinically meaningful improvement in motor function.

The TOPAZ phase 2 clinical trial in patients with type 2 and type 3 SMA is ongoing in the extension phase. The U.S. Food and Drug Administration has granted Orphan Drug designation and Rare Pediatric Disease designation, and the European Medicines Agency has granted Priority Medicines (PRIME) designation and Orphan Medicinal Product designation, to apitegromab for the treatment of SMA.

The study included three cohorts and used the Hammersmith scale, a standardized test of function in patients with SMA. The first cohort involved patients 5 to 21 years of age, ambulatory type 3, 20 mg/kg dose monotherapy and in conjunction with nusinersen. They had a mean change from baseline in Revised Hammersmith Scale of a 0.3-point decline. Cohort 2 included patients 5-21 years of age with type 2 and non-ambulatory type 3 who initiated nusinersen at or before age 5 20 mg/kg dose. Those patients had a mean change from baseline in Hammersmith Functional Motor Scale Expanded of a 0.6-point improvement. Cohort 3 included patients 2 years of age or older with type 2 SMA who initiated nusinersen before age 5. They had a mean change of 7.1-point improvement in the 20 mg/kg dose and a 5.3-point improvement in the 2 mg/kg dose arms.

“These top-line 12-month data provide further support towards establishing apitegromab as a potential first muscle-directed therapy for patients with SMA,” said Yung Chyung, chief medical officer of Scholar Rock. “The findings also offer important insights into myostatin biology and our scientific approach of targeting the latent forms of growth factors.

Incidence and severity of adverse events were consistent with the underlying patient population and background therapy. Five most frequently reported treatment-emergent adverse events included headache (24 percent), fever (22 percent), upper respiratory tract infection (22 percent), cough (22 percent), and nasopharyngitis (21 percent).

The company plans to initiate a pivotal trial in SMA by the end of 2021 and explore its potential in additional disease areas.


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