Scholar Rock reported positive data from a six-month interim analysis of the ongoing phase 2 TOPAZ clinical trial. The open label trial is evaluating SRK-015 across three cohorts of patients with type 2 and type 3 Spinal Muscular Atrophy (SMA). According to the data, administration of SRK-015 every four weeks (Q4W) led to improvements in Hammersmith scale scores in all three cohorts, meeting the primary efficacy endpoint. Top-line data from the 12-month treatment period are anticipated in the second quarter of 2021.
TOPAZ enrolled 58 patients with Type 2 and Type 3 SMA across 16 study sites in the U.S. and Europe. The patients ranged in age from 2 to 21 years old and were placed in one of three cohorts: Ambulatory Type 3 SMA (cohort 1), Type 2 SMA / Non-Ambulatory Type 3 SMA (cohort 2) or Type 2 SMA (cohort 3). All patient cohorts received 20 mg/kg of SRK-015 Q4W either as a monotherapy or in conjunction with an approved SMN upregulator therapy (nusinersen). In cohort 3, a low dose was added (2 mg /kg SRK-015 Q4W). The primary endpoint for Cohort 1 is change from baseline up to 12 months in the Revised Hammersmith Scale (RHS). The primary endpoint for Cohorts 2 and 3 is change from baseline up to 12 months in Hammersmith Functional Motor Scale Expanded (HFMSE).
The pre-planned interim analysis was conducted following a six-month treatment period across all three study cohorts. Three patients (one in Cohort 2 and two in Cohort 3) each missed three doses of SRK-015 and the six-month interim analysis timepoint due to COVID-19-related site access restrictions; the six-month timepoint from these patients was not included in the interim analysis.
At the six-month interim analysis timepoint mean increases from baseline in Hammersmith scale scores were observed in all three cohorts. 67% of total patients achieved ≥1 point improvement in Hammersmith scores and 35% of total patients achieved ≥3 point increase in Hammersmith scores.
In Cohort 3 dose response in the primary efficacy endpoint was observed across all evaluated timepoints. The high-dose arm of Cohort 3 attained a 5.6 point mean improvement from baseline in the Hammersmith Functional Motor Scale Expanded (HFMSE) as compared to the low dose arm, which attained a 2.4 point mean improvement at the six-month interim analysis timepoint.
No safety signals were identified. The most frequently reported adverse reactions included headache, upper respiratory tract infection, pyrexia, nasopharyngitis, and cough.
SRK-015 is a selective inhibitor of the activation of myostatin. 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 myostatin with SRK-015 may promote a clinically meaningful increase in muscle strength.
The U.S. FDA has granted Orphan Drug Designation (ODD) and Rare Pediatric Disease (RPD) designation, and the European Commission (EC) has granted Orphan Medicinal Product Designation, to SRK-015 for the treatment of SMA.
About Spinal Muscular Atrophy
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.