Scholar Rock Announces Positive Interim Results from Phase 1 Trial of SRK-015 in Healthy Volunteers and Updates on Future Development Plans
- Favorable Safety Profile Across All Tested Doses Supports Initiation of a Phase 2 Trial in Patients with Spinal Muscular Atrophy (SMA)
- Pharmacodynamic Results Demonstrate Robust and Sustained Target Engagement of Latent Myostatin
- Phase 2 Trial Initiation Expected by the End of 1Q19 with Interim Safety and Efficacy Analysis Following Six Months of Treatment Expected in 1H20
- Company to Host Conference Call and Webcast on
February 26, 2019at 8:00 a.m. ET
“We are very excited with the progress to date in the Phase 1 trial of SRK-015 as we continue to work towards developing our lead antibody candidate as a potential first muscle-directed therapy for the treatment of SMA,” said
Phase 1 Trial Design and Interim Results
Trial Design. The randomized, double-blind, placebo-controlled Phase 1 clinical trial was designed to evaluate the safety and tolerability of intravenously administered SRK-015, assess the PK/PD profile, and inform dosing for the Phase 2 trial.
- Single-Ascending Dose (SAD): Enrolled 40 adult healthy volunteers, randomized 3:1 to receive a single dose of SRK-015 or placebo, and evaluated doses of 1, 3, 10, 20 and 30 mg/kg.
- Multiple-Ascending Dose (MAD): Enrolled 26 adult healthy volunteers, randomized 3:1 to receive SRK-015 or placebo every two weeks for a total of three doses (Day 0, 14 and 28). The MAD portion of the trial evaluated doses of 10, 20 and 30 mg/kg.
The interim analysis was conducted with data from all subjects in the completed SAD portion of the trial and available data for all subjects in the MAD portion of the trial, including through Day 35 for the highest 30 mg/kg dose cohort and longer follow-up for the 10 and 20 mg/kg dose cohorts. Follow-up in the MAD portion of the trial is ongoing and full clinical results from the Phase 1 trial will be presented at a scientific conference this year.
Safety and Immunogenicity Data. SRK-015 was observed to be well tolerated with no dose-limiting toxicities identified up to the highest evaluated dose of 30 mg/kg. There were no deaths, no discontinuations due to a treatment-related adverse event (AE), no treatment-related serious AEs (SAE), and no hypersensitivity reactions. In the SAD portion of the trial, AEs were observed in 30% (9/30) of SRK-015-treated subjects and 50% (5/10) of placebo-treated subjects. In the MAD portion of the trial, AEs were observed in 30% (6/20) of SRK-015-treated subjects and 67% (4/6) of placebo-treated subjects. A single SAE (gallstone-induced pancreatitis) was observed and assessed by the trial investigator as unrelated to SRK-015 treatment. Immunogenicity as evaluated by anti-drug antibody testing was negative for all subjects in the SAD portion of the trial and data for subjects in the MAD portion of the trial are pending completion of the Phase 1 trial.
Biomarker/Pharmacodynamic Data. PD was evaluated through a proprietary, exploratory biomarker assay developed by
Pharmacokinetic Data. Based on data from the SAD, SRK-015 displayed a PK profile consistent with what is generally observed for monoclonal antibodies. Drug exposure was dose-proportional and the serum half-life was 23-33 days across the SRK-015 dose groups, supporting the investigation of a once every four-week dosing regimen in the Phase 2 trial.
“These interim Phase 1 data provide initial proof-of-mechanism for the pharmacologic potential of SRK-015, and more broadly, Scholar Rock’s therapeutic approach of specifically targeting the latent forms of growth factors,” said Nagesh Mahanthappa, Ph.D, President and CEO of Scholar Rock. “Through our discovery efforts, we have built a robust pipeline of highly specific growth factor modulators across a diverse range of therapeutic areas and are eagerly working to advance these potential therapies to serve patients with unmet medical needs.”
Phase 2 (TOPAZ) Trial Overview
Scholar Rock’s preclinical data and translational insights highlight the promising potential of myostatin as a drug target in SMA, and positive interim results from the Phase 1 study demonstrate that SRK-015 may have the necessary pharmacologic profile to modulate this pathway.
An interim analysis assessing safety and efficacy is planned for each cohort of the Phase 2 trial, encompassing a subset of patients with at least 6 months of treatment exposure. These interim results by cohort are expected in the first half of 2020. Top-line results for the full 12-month treatment period are expected starting in the fourth quarter of 2020 and through the first quarter of 2021. In addition, analyses of preliminary PK and PD data are planned by the end of 2019.
Conference Call Information
SRK-015 is a selective inhibitor of the activation of myostatin and is an investigational product candidate for the treatment of patients with spinal muscular atrophy (SMA). Myostatin, a member of the TGF-beta 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 mass and strength. A Phase 1 clinical trial in healthy volunteers is ongoing and a Phase 2 trial is expected to initiate by the end of the first quarter of 2019. The U.S. Food and Drug Administration (
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
About Scholar Rock
Scholar Rock is a clinical-stage biopharmaceutical company focused on the discovery and development of innovative medicines for the treatment of serious diseases in which signaling by protein growth factors plays a fundamental role. Scholar Rock is creating a pipeline of novel product candidates with the potential to transform the lives of patients suffering from a wide range of serious diseases, including neuromuscular disorders, cancer, fibrosis and anemia. Scholar Rock’s newly elucidated understanding of the molecular mechanisms of growth factor activation enabled it to develop a proprietary platform for the discovery and development of monoclonal antibodies that locally and selectively target these signaling proteins at the cellular level. By developing product candidates that act in the disease microenvironment, the Company intends to avoid the historical challenges associated with inhibiting growth factors for therapeutic effect.
Scholar Rock® is a registered trademark of
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Scholar Rock’s future expectations, plans and prospects, including without limitation, Scholar Rock’s expectations regarding the potential of SRK-015 as a therapy in SMA and the timeline for and progress in developing SRK-015. The use of words such as “may,” “might,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “potential,” or “continue,” and other similar expressions are intended to identify such forward-looking statements. All such forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include those risks more fully discussed in the section entitled "Risk Factors" in Scholar Rock’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2018, as well as discussions of potential risks, uncertainties, and other important factors in Scholar Rock’s subsequent filings with the Securities and Exchange Commission. Any forward-looking statements represent Scholar Rock’s views only as of today and should not be relied upon as representing its views as of any subsequent date. All information in this press release is as of the date of the release, and Scholar Rock undertakes no duty to update this information unless required by law.
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