Scholar Rock Announces Initiation of Patient Dosing in Phase 2 Trial of SRK-015 in Spinal Muscular Atrophy
09 May 2019 - 6:05AM
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 the initiation of patient dosing in the Phase 2
clinical trial of SRK-015, a highly specific inhibitor of myostatin
activation, in Type 2 and Type 3 Spinal Muscular Atrophy (SMA).
All patients will receive SRK-015 once every four weeks
either as a monotherapy or in conjunction with an approved SMN
upregulator therapy. This Phase 2 trial is supported by
interim results from the Phase 1 trial in healthy volunteers that
showed favorable safety and tolerability, pharmacodynamic (PD), and
pharmacokinetic (PK) results as well as preclinical data that
highlight the promising potential of myostatin as a drug target in
SMA.
“Despite real advances improving upon the natural history of SMA
with therapies that increase levels of the deficient SMN protein,
individuals with SMA nonetheless experience a range of weakness
from mild to profound,” said Thomas Crawford, M.D., Professor of
Neurology at Johns Hopkins and Lead Principal Investigator of the
TOPAZ trial. “Muscle-directed therapy is the next step
towards addressing residual weakness in individuals with SMA. I
believe SRK-015 holds real promise to potentially improve their
overall motor function.”
“The initiation of patient dosing in our Phase 2 TOPAZ study
marks an important milestone towards our goal of establishing
SRK-015 as the first muscle-directed therapy to help address the
functional deficits that continue to affect patients with SMA
despite available therapies,” said Yung Chyung, M.D., Chief Medical
Officer of Scholar Rock. “Results from this Phase 2 trial
will further our understanding on the potential clinical benefits
of targeting the latent form of myostatin and open up the
possibility of investigating other neuromuscular disorders.”
TOPAZ Phase 2 Trial Design
The Phase 2 proof-of-concept trial will evaluate the safety and
efficacy of SRK-015 dosed intravenously every four weeks (Q4W) over
a 12-month treatment period. The trial is anticipated to
enroll approximately 55 patients with Type 2 or Type 3 SMA in the
U.S., Canada, and Europe across three distinct and parallel
cohorts.
- Cohort 1 has an open-label, single-arm design
and will enroll approximately 20 patients ages 5 through 21 with
ambulatory Type 3 SMA. Patients will be treated with 20 mg/kg
of SRK-015 Q4W as monotherapy or in conjunction with an approved
SMN upregulator therapy. The primary objectives of the cohort
are to assess safety and the mean change from baseline in Revised
Hammersmith Scale (RHS) over 12 months of treatment. Key
secondary assessments include the proportion of patients attaining
various thresholds of change from baseline in RHS and change from
baseline in 6-minute walk test (6MWT).
- Cohort 2 has an open-label, single-arm design
and will enroll approximately 15 patients ages 5 through 21 with
Type 2 or non-ambulatory Type 3 SMA and who are already receiving
treatment with an approved SMN upregulator. Patients will be
treated with 20 mg/kg of SRK-015 Q4W in conjunction with an
approved SMN upregulator therapy. The primary objectives of
the cohort are to assess safety and the mean change from baseline
in Hammersmith Functional Motor Scale Expanded (HFMSE) over 12
months of treatment. Key secondary assessments include the
proportion of patients attaining various thresholds of change from
baseline in HFMSE and change from baseline in Revised Upper Limb
Module (RULM).
- Cohort 3 has a randomized, double-blind,
parallel arm design and will evaluate the effects of SRK-015 in the
setting of early intervention with an SMN upregulator therapy.
This cohort will enroll approximately 20 patients with Type 2
SMA who are at least two years of age and initiated treatment with
an approved SMN upregulator before five years of age.
Patients will be randomized 1:1 to be treated with either 2 mg/kg
or 20 mg/kg of SRK-015 Q4W. The primary objectives of the
cohort are to assess safety and the mean change from baseline in
HFMSE over 12 months of treatment. Key secondary measures
include the proportion of patients attaining various thresholds of
change from baseline in HFMSE and change from baseline in RULM.In
cohort 3, a low dose arm of 2 mg/kg has been included for dose
exploration purposes. The relationship between drug exposure and
therapeutic effect over time may be evaluated by characterizing and
comparing the time course of clinical effect for the 2 mg/kg and 20
mg/kg arms.
An interim analysis is planned for each cohort, encompassing a
subset of patients with at least six 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 pharmacokinetic (PK) and pharmacodynamic
(PD) data from a subset of patients are planned by the end of
2019.
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 muscle mass and strength. 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 Annual Report on Form 10-K for the
quarter and full year ended December 31, 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.
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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