Apitegromab Demonstrates Safety, Efficacy in Spinal Muscular Atrophy
Scholar Rock noted that the topline results from the 52-week treatment period are expected to be announced in the second quarter of 2021.
Interim results from the phase 2 TOPAZ trial (NCT03921528) demonstrated that treatment with apitegromab (SRK-015; Scholar Rock) is safe and improves motor function in patients with spinal muscular atrophy (SMA). The data also suggest that apitegromab has the potential to be the first muscle-directed therapy for patients with SMA.1
The data was presented at
Apitegromab, a fully human monoclonal antibody, binds to both proMyostatin and latent myostatin and inhibits tolloid-mediated cleavage of latent myostatin, thereby preventing the release of the mature, active myostatin.
Treatment with apitegromab resulted in 67% of total patients achieving greater than 1 point improvement In Hammersmith Functional Motor Scale (HFMSE) scores at 6 months. Furthermore, 35% of the total population of 55 patients achieved a greater than 3-point increase in HFMSE scores as well.
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The drug was administered by intravenous (IV) infusion every 4 weeks in subjects with SMA type 2 and type 3 across 3 study cohorts. Subjects in cohort 1 (ambulatory Type 3; n = 23) who received 20 mg of the drug as monotherapy or as adjunctive treatment to nusinersen (Spinraza; Biogen), had a pooled mean changed in baseline Revised Hammersmith Scale (RHS) scores of 0.5 (95% CI, –1.1 to 2.2).
Cohort 2 (n = 14) and 3 (n = 18) included type 2 and non-ambulatory type 3 subjects, who received apitegromab (Cohort 2: 20mg/kg; Cohort 3: 2mg/kg or 20mg/kg) as an adjunctive treatment to nusinersen. At the end of the study period, those in Cohort 2 achieved a mean change in HFMSE scores of 1.4 (95% CI, 0.1-2.7).
Dose response in primary efficacy end point, or change in Hammersmith scale scores, were observed in Cohort 3, with the high dose attaining a 5.6-point mean improvement over baseline at 6-months compared to the low dose (2.4-point mean).
Incidence and severity of adverse events (AEs) were consistent with underlying patient population and background therapy. Treatment-emergent AEs (TEAEs) were common in most subjects across all 3 cohorts, with headache being the most common, followed by upper respiratory tract infection, pyrexia, nasopharyngitis, cough, and vomiting.
Previously, early-phase data suggest that the investigational agent has sustained and robust target engagement. Pharmacokinetic data revealed that drug exposure was dose-proportional and SRK-015’s serum half-life was 23 to 33 days across the different dose cohorts. The pharmacokinetic profile displayed by SRK-015 was consistent with what is regularly observed for monoclonal antibodies.2
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REFERENCES
1. Place A, et al. Apitegromab, a novel high-affinity anti-proMyostatin monoclonal antibody for treating spinal muscular atrophy: results of a phase 2 interim analysis. Presented at MDA Clinical and Scientific Conference 2021; March 15-18.
2. Scholar Rock Announces Positive Final Results from Phase 1 Clinical Trial of SRK-015 in Healthy Volunteers. News release. June 5, 2019. Accessed March 16, 2021. apnews.com/Globe%20Newswire/cffc9244c4efe20ea3ca3091ec2c12a5.
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