The new phase 3 trial called SAPPHIRE will investigate the safety and efficacy of apitegromab as an add-on treatment to background survival motor neuron therapy for patients with spinal muscular atrophy (SMA) type 2 or 3 who are not able to walk, according to a press release by Scholar Rock.

This randomized, double-blind, placebo-controlled study aims to enroll around 156 patients aged 2 to 12 years. Participants will be treated with 10 mg per kg of apitegromab, 20 mg per kg of apitegromab, or a placebo intravenously on top of their background nusinersen or risdiplam treatment every 4 weeks for 1 year.

Apitegromab is a selective myostatin activation inhibitor. Myostatin is a protein that inhibits muscle growth, and inhibiting its activation may improve muscle function. It has already been evaluated in a phase 2 proof of concept trial called TOPAZ, which informed the design of SAPPHIRE.

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The primary endpoint of the trial will be the mean change in the Expanded Hammersmith Functional Motor Scale (HFMSE) score from baseline after 12 months. Secondary endpoints will include the proportion of patients with an increase of more than 3 points in the HFMSE score. Motor developmental milestones, pharmacokinetics, pharmacodynamics, and antidrug antibody formations will also be evaluated.

The trial will investigate the safety, tolerability, and efficacy of apitegromab in an exploratory population of 48 patients aged 13 to 21 years who will receive either 20 mg per kg of apitegromab or a placebo.

At the end of the 12 month period, all patients will have the opportunity to enroll in an open-label extension study that will further investigate the safety and tolerability of apitegromab as well as to characterize its long-term efficacy in an exploratory manner.

“We are excited to advance to the pivotal trial phase of apitegromab development through SAPPHIRE,” Nagesh Mahanthappa, PhD, interim chief executive officer of Scholar Rock said.


Scholar Rock announces design of phase 3 SAPPHIRE clinical trial evaluating apitegromab in non-ambulatory patients with type 2 and type 3 spinal muscular atrophy (SMA). News release. Scholar Rock; November 30, 2021.