Phase 2 Trial Drug Apitegromab Shows Progress for Spinal Muscular Atrophy Patients


The phase 2 TOPAZ trial demonstrated treatment is safe and improves motor function in patients with SMA.

This article was originally published on NeurologyLive.

Apitegromab (SRK-015; Scholar Rock) has the potential to be the first muscle-directed therapy for patients with spinal muscular atrophy (SMA), according to results from the phase 2 TOPAZ trial.

The trial (NCT03921528) demonstrated treatment is safe and improves motor function in patients with SMA.

Data from the trial was presented at Muscular Dystrophy Association (MDA) Clinical and Scientific Conference 2021, March 15–18, by Amy Place, PhD, senior director, global medical affairs, Scholar Rock. These are the first clinical data showing the potential therapeutic benefits of Scholar Rock’s novel scientific platform of inhibiting the activation of latent myostatin. Topline results are expected to be announced in the second quarter of 2021.

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.

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.

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