Benzinga | Nov 30, 2021 05:04PM EST

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

Scholar Rock (NASDAQ:SRRK), a clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, today announced the study design for SAPPHIRE, a Phase 3 trial of apitegromab, a selective inhibitor of the activation of latent myostatin. This pivotal trial will evaluate the efficacy and safety of apitegromab in patients with non-ambulatory Type 2 and Type 3 spinal muscular atrophy (SMA), which is estimated to represent approximately two-thirds of the overall SMA patient population. Study start-up activities for SAPPHIRE have commenced.

"Despite the important progress in SMA treatment offered by SMN therapies, there continues to be significant unmet medical need, and we believe that apitegromab has the potential to improve motor function as add-on to background SMN therapy and transform the lives of patients with SMA," said Nagesh Mahanthappa, Ph.D., Interim CEO. "We are excited to advance to the pivotal trial phase of apitegromab development through SAPPHIRE."

SAPPHIRE Trial Design

SAPPHIRE is a randomized, double-blind, placebo-controlled, phase 3 clinical trial. Approximately 156 patients aged 2-12 years old with non-ambulatory Type 2/3 SMA are anticipated to be enrolled in the main efficacy population. Patients will be randomized 1:1:1 to receive for 12 months either apitegromab 10 mg/kg, apitegromab 20 mg/kg, or placebo by intravenous (IV) infusion every 4 weeks added on top of background SMN treatment. Patients receiving the background SMN treatment of nusinersen as well as patients receiving background SMN treatment of risdiplam will both be eligible for enrollment.

Additional key elements of the study design include the following:

* At baseline, all patients will be required to be in the chronic maintenance phase of SMN treatment, corresponding to > 6 months of prior treatment in the case of risdiplam or > 10 months of prior treatment in the case of nusinersen.

* Randomization will be stratified by both the background SMN treatment (nusinersen vs. risdiplam) as well as the age at which SMN treatment had been initiated (< 5 years vs. > 5 years).

* The primary efficacy endpoint will evaluate the mean change from baseline in the Expanded Hammersmith Functional Motor Scale (HFMSE) total score after 12 months of treatment.

* Additional endpoints will evaluate safety, proportion of patients with >3-point HFMSE increase, Revised Upper Limb Module (RULM), and World Health Organization (WHO) motor developmental milestones, pharmacokinetics, pharmacodynamics, anti-drug antibody, and other outcome measures.

In addition, the trial provides the opportunity for an interim analysis when at least 50% of patients in the main efficacy population (age 2-12 years) have completed 12 months of treatment.

Separately from the main efficacy population, an exploratory population of 48 patients aged 13-21 years old with non-ambulatory Type 2/3 SMA will be evaluated. These patients will be randomized 2:1 to receive either apitegromab 20 mg/kg or placebo added to background SMN treatment with nusinersen or risdiplam. In this subpopulation of older individuals with SMA, the safety and tolerability of apitegromab will be characterized, and efficacy will also be evaluated in an exploratory, nonpowered manner.

To further characterize apitegromab in SMA, upon completion of the 12-month treatment period, all patients will be offered the option of enrolling in an open-label extension study. In this open-label extension, the safety and tolerability of apitegromab will be evaluated, along with an exploratory characterization of longer-term efficacy. In addition, the TOPAZ extension continues to follow patients from TOPAZ and evaluate the longer-term efficacy and safety of apitegromab. Among the 57 patients who completed the 12-month TOPAZ treatment period, 55 patients continue to participate in the extension period as of November 30, 2021.

SAPPHIRE is planned to enroll across 55 sites globally, including in the U.S. and Europe, and study start-up activities have commenced. For more information about SAPPHIRE, visit www.clinicaltrials.gov.

"We are encouraged and motivated by the positive results of the TOPAZ Phase 2 proof of concept trial, which informed the design of SAPPHIRE to evaluate the therapeutic potential of apitegromab in SMA," said Yung Chyung, M.D., CMO. "Building on the solid foundation of TOPAZ, our Phase 3 trial and the broader program are aimed at advancing the development of apitegromab towards our aspiration of transforming the lives of patients with SMA."