Scholar Rock Announces Positive Final Results from Phase 1 Clinical Trial of SRK-015 in Healthy Volunteers
June 03 2019 - 3:05PM
Scholar Rock Holding Corporation (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 positive final top-line results from the Phase 1
clinical trial of its product candidate, SRK-015, a highly specific
inhibitor of myostatin activation, in healthy adult volunteers.
Consistent with previously announced interim findings, the
final results showed robust and sustained target engagement and no
apparent safety signals were observed across all tested
doses. Detailed results from the Phase 1 trial will be
presented at the Cure SMA Annual Conference being held June 28-July
1, 2019 in Anaheim, CA.
“We are pleased to be presenting the Phase 1 SRK-015 trial
results at the upcoming Cure SMA annual conference as these data
provide initial safety and mechanistic insights for SRK-015 and
support our Phase 2 program,” said Yung Chyung, M.D., Chief Medical
Officer of Scholar Rock. “With the recent initiation of dosing in
the TOPAZ Phase 2 clinical trial, we are now evaluating SRK-015’s
potential to address motor functional impairment in patients with
spinal muscular atrophy.”
“The pharmacodynamic results from the Phase 1 trial offer
initial proof-of-mechanism for Scholar Rock’s unique therapeutic
approach of targeting the latent form of growth factors,” said
Nagesh Mahanthappa, Ph.D., President and CEO of Scholar Rock. “We
have advanced the SRK-015 Phase 2 program in patients with SMA and
look forward to the interim safety and efficacy results as well as
continuing to progress our robust pipeline of highly specific
growth factor modulators across a diverse range of therapeutic
areas.”
Phase 1 Final Top-line Results
Safety and Immunogenicity Data. SRK-015 was
observed to be well-tolerated in the Phase 1 trial with no
dose-limiting toxicities identified up to the highest evaluated
dose of 30 mg/kg.
- In the single-ascending dose (SAD) portion of the trial,
adverse events (AEs) were observed in 30 percent (9/30) of
SRK-015-treated subjects and 50 percent (5/10) of placebo-treated
subjects.
- In the multiple-ascending dose (MAD) portion of the trial, AEs
were observed in 35 percent (7/20) of SRK-015-treated subjects and
67 percent (4/6) of placebo-treated subjects.
- There were no discontinuations due to a treatment-related AE,
no hypersensitivity reactions, and no deaths. A single
serious AE (SAE) of gallstone-induced pancreatitis was observed in
an SRK-015-treated subject and was assessed by the trial
investigator as unrelated to treatment.
- Immunogenicity as evaluated by anti-drug antibody testing was
negative for all SRK-015 treated subjects in the trial.
Biomarker/Pharmacodynamic (PD) Data.
Target engagement was shown in the Phase 1 trial
through increases from baseline in levels of latent
myostatin.
- The levels of target engagement attained a plateau after a
single dose of SRK-015 at 3 mg/kg or greater, suggesting target
saturation. This plateau was sustained up to Day 84 after a
single dose at 20 mg/kg.
- This durability of effect was further shown in the MAD portion
of the trial, during which the plateau was sustained up to at least
Day 140 after three doses given once every two weeks at 20 mg/kg or
30 mg/kg.
- In contrast, no meaningful change was observed in the latent
myostatin biomarker concentrations in subjects who received
placebo.
PD was evaluated through a proprietary, exploratory biomarker
assay developed by Scholar Rock that measures serum concentrations
of latent myostatin. This assay was used previously to
measure target engagement in preclinical studies in healthy animals
and a mouse model of SMA.
Pharmacokinetic (PK) Data. Drug exposure to
SRK-015 was dose-proportional and SRK-015’s serum half-life was
23-33 days across dose cohorts. In these respects, SRK-015
displayed a PK profile consistent with what is commonly observed
for monoclonal antibodies.
Phase 1 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 and PD
profile, and inform dosing for the Phase 2 trial.
- Single-Ascending Dose: 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: 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.
About SRK-015 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 motor function. A Phase 2 clinical
trial in patients with Type 2 and Type 3 SMA is ongoing. The
U.S. Food and Drug Administration (FDA) has granted Orphan Drug
Designation (ODD), and the European Commission (EC) has granted
Orphan Medicinal Product Designation, to SRK-015 for the treatment
of SMA. The effectiveness and safety of SRK-015 have not been
established and SRK-015 has not been approved for any use by the
FDA or any other regulatory agency.
About SMASpinal 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 the United States and Europe. It is
characterized by the loss of motor neurons, atrophy of the
voluntary muscles of the limbs and trunk and progressive muscle
weakness. The underlying pathology of SMA is caused by insufficient
production of the SMN (survival of motor neuron) protein, essential
for the survival of motor neurons, and is encoded by two genes,
SMN1 and SMN2. While there has been progress in the
development of therapeutics that address the underlying SMA genetic
defect, there continues to be a high unmet need for therapeutics
that directly address muscle atrophy.
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 believes its focus on biologically validated growth factors
may facilitate a more efficient development path. For more
information, please visit www.ScholarRock.com or
follow Scholar Rock on Twitter (@ScholarRock) and
LinkedIn (https://www.linkedin.com/company/scholar-rock/).
Scholar Rock® is a registered trademark of Scholar Rock,
Inc.
Forward-Looking StatementsThis 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 future expectations, plans and
prospects, including without limitation, 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 the risks that earlier
preclinical and clinical data and testing of SRK-015 may not be
predictive of the results or success of additional clinical trials,
the development of SRK-015 will take longer and/or cost more than
planned, SRK-015 will not receive regulatory approval
and 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 March 31, 2019, 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.
Scholar Rock Contact:
Investors/Media
Catherine Hu, 917-601-1649
chu@scholarrock.com
Media Contact:
The Yates Network
Kathryn Morris, 914-204-6412
kathryn@theyatesnetwork.com
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