- Sizable and
sustained improvement in Hammersmith Functional Motor
Scale-Expanded (HFMSE) scores observed at 24 months
- Substantial
increase in Revised Upper Limb Module (RULM) scores observed at 24
months
- No serious
safety risks identified over 24 months
- Enrollment
progressing in pivotal Phase 3 SAPPHIRE registrational trial
- Scholar
Rock to host webcast today at 8:30 a.m. ET
Scholar Rock (NASDAQ: SRRK), a Phase 3, clinical-stage
biopharmaceutical company focused on the treatment of serious
diseases in which protein growth factors play a fundamental role,
today announced new data from the Phase 2 TOPAZ trial extension
period evaluating patient outcomes after 24-months of treatment,
which support sustained and continued improvement with apitegromab
for non-ambulatory patients with Types 2 and 3 SMA receiving an SMN
therapy. Detailed results are being presented by Thomas Crawford,
M.D. of Johns Hopkins Medicine and the lead principal investigator
of the TOPAZ trial, during a podium presentation at the Cure SMA
Research & Clinical Care Meeting today at 11:20 a.m. PST.
"The 24-month results provide long-term data and evidence,
underscoring the findings of the 12-month primary treatment period
of the TOPAZ trial in which patients receiving apitegromab
experienced sizable motor function gains,” said George Nomikos,
M.D., Ph.D., Senior Vice President of Clinical Sciences, Head of
Muscle Therapeutic Area of Scholar Rock. “This durability and
continued increase in motor function support the transformative
potential of apitegromab for patients suffering with SMA.”
“These data support apitegromab’s potential to meaningfully
improve the lives of non-ambulatory patients with Types 2 and 3
SMA,” said Nagesh Mahanthappa, Ph.D., Founding Chief Executive
Officer & President of Scholar Rock. “As a company, we are
dedicated to the SMA community and are urgently enrolling patients
in our ongoing pivotal Phase 3 SAPPHIRE trial.”
TOPAZ evaluated apitegromab across a broad age range (2-21
years) of patients with Types 2 and 3 SMA. All 35 non-ambulatory
patients (Cohorts 2 and 3) and 12 of 23 ambulatory patients (Cohort
1) were receiving nusinersen maintenance therapy. The primary
efficacy endpoint for the non-ambulatory population was mean change
from baseline in HFMSE. Additional endpoints included mean change
from baseline in RULM, an assessment specifically designed for
upper limb function in patients with SMA. The HFMSE is a validated
measure for the assessment of gross motor function in SMA, while
the RULM is validated to evaluate upper limb motor performance by
evaluating tasks which correspond to the ability to perform various
everyday activities with their hands and arms.
For this 24-month evaluation, an observed case analysis was
conducted, which pooled all the non-ambulatory patients (Cohorts 2
and 3) and was based upon the available data for given timepoints.
This analysis population included patients receiving either low
dose (2 mg/kg) or high dose (20 mg/kg) apitegromab (inclusive of
patients in Cohort 3 who switched from 2 mg/kg to 20 mg/kg in Year
2) and did not exclude any patients who had missed apitegromab
doses due to study site access restrictions from COVID-19.
Non-ambulatory patients (age range of 2 to 21 years old)
with valid HFMSE assessments had sizable, sustained gains in HFMSE
scores at 24 months from baseline (prior to first dose of
apitegromab), while RULM scores continued to increase at 24 months.
The mean change from baseline results for non-ambulatory patients
showed:
12-Month Data
24-Month Data
Pooled non-ambulatory
pts
24-Month Data
*excluding pts w/scoliosis
surgery
Mean Change from Baseline in
HFMSE (95% CI)
3.6 points
(95% CI: 1.2, 6.0)
N=32
4.0 points
(95% CI: 1.5, 6.5)
N=29
4.4 points
(95% CI: 2.0, 6.9)
N=28
Mean Change from Baseline in
RULM (95% CI)
1.3 points
(95% CI: 0.2, 2.3)
N=31
1.9 points
(95% CI: 0.8, 3.0)
N=33
2.3 points
(95% CI: 1.2, 3.4)
N=30
*Three patients in the non-ambulatory group underwent scoliosis
surgery in year 2, which has been reported to negatively impact
HFMSE scores for a considerable period afterwards1. This
analysis excluded post-surgery data of these patients.
Dose response continued to be observed across the 24 months of
apitegromab administration based upon HFMSE scores and
pharmacodynamic data (target engagement as measured by serum latent
myostatin concentrations), with signs that there may be further
HFMSE increases as non-ambulatory patients originally receiving the
low dose switched to the high dose treatment.
Data at 24-months for ambulatory patients with Type 3 SMA
(Cohort 1) suggest stability of Revised Hammersmith Scale (RHS)
scores in patients receiving 20 mg/kg of apitegromab and
nusinersen. The mean RHS change from baseline at 24-months was ‑0.7
points (95% CI: -3.1, 1.7) for the apitegromab and nusinersen
subgroup (n=10) and ‑2.8 points (95% CI: -8.4, 2.8) for the
apitegromab monotherapy subgroup (n=11). A subset of individuals in
Cohort 1(n=21) had RHS improvements, as reflected by 42.9% (9/21)
and 23.8% (5/21) of patients having ≥1-point and ≥3-point RHS
increases from baseline at 24 months respectively.
Of the 55 patients who completed the 24-month TOPAZ extension
period, 54 have opted to continue treatment in the 36-month
extension period.
Consistent with the 12-month safety data, no serious safety
risks were identified as part of the analysis of the cumulative
24-month data. The incidence and severity of adverse events were
consistent with the underlying patient population and background
therapy. The five most common treatment-emergent adverse events
(TEAEs) were headache, pyrexia, upper respiratory tract infection,
cough, and nasopharyngitis. No deaths or serious adverse reactions
have been observed with apitegromab. A total of 14 serious TEAEs
have been reported over the 24-month treatment period, all assessed
by the respective trial investigator as unrelated to
apitegromab.
Details of the podium presentation at SMA Research &
Clinical Care Meeting are as follows:
Title: TOPAZ Extension: 24-Month Efficacy and Safety of
Apitegromab in Patients with Later-Onset Spinal Muscular Atrophy
(Type 2 and Type 3 SMA)
Presenter: Thomas Crawford, M.D., lead principal
investigator of the TOPAZ trial and Professor of Neurology and
Pediatrics; Johns Hopkins University.
Clinical Drug Development Session: June 17 at 11:20 -
11:40 a.m. PST (Abstract #28)
Conference Call/Webcast:
Scholar Rock will host a conference call and audio webcast to
discuss topline 24-month data from the Phase 2 TOPAZ clinical trial
on June 17, 2022 at 8:30 a.m. Eastern Time. To participate in the
call, please dial 833-519-1308 (domestic) or 914-800-3874
(international) and refer to conference ID: 6495684. A webcast of
the call will also be available on the Investors & Media
section of the Scholar Rock website at
http://investors.scholarrock.com. An archived replay of the webcast
will be available on Scholar Rock’s website at:
https://scholarrock.com/ for approximately 180 days following the
presentation.
About the Phase 2 TOPAZ Trial
The TOPAZ trial is an ongoing proof-of-concept, open-label phase
2 trial evaluating the safety and efficacy of apitegromab in
patients with Types 2 and 3 SMA. In the main treatment period,
patients were dosed intravenously every four weeks as monotherapy
or with nusinersen, an approved SMN therapy. The trial enrolled 58
patients in the U.S. and Europe. The primary efficacy endpoints
were mean change from baseline in Revised Hammersmith Scale (RHS)
score at 12 months for the ambulatory population (Cohort 1), and
mean change from baseline in HFMSE score at 12 months for
non-ambulatory population (Cohorts 2 and 3). The trial also
includes multiple 12-month extension periods designed to evaluate
longer-term patient outcomes.
About the Phase 3 SAPPHIRE Trial
SAPPHIRE is an ongoing randomized, double-blind,
placebo-controlled, phase 3 clinical trial evaluating the safety
and efficacy of apitegromab in non-ambulatory patients with Types 2
and 3 SMA who are receiving SMN therapy (either nusinersen or
risdiplam). Approximately 156 patients aged 2-12 years old are
anticipated to be enrolled in the main efficacy population. These
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. An exploratory population
of approximately 48 patients aged 13-21 years old will also
separately be evaluated. These patients will be randomized 2:1 to
receive either apitegromab 20 mg/kg or placebo. 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.
SAPPHIRE is expected to enroll 55 sites in the U.S. and Europe. For
more information about SAPPHIRE, visit www.clinicaltrials.gov.
About Apitegromab
Apitegromab 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 TGFβ 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, including humans. Scholar Rock believes
that inhibiting myostatin activation with apitegromab may promote a
clinically meaningful improvement in motor function in patients
with SMA. The U.S. Food and Drug Administration (FDA) has granted
Fast Track, Orphan Drug and Rare Pediatric Disease designations,
and the European Medicines Agency (EMA) has granted Priority
Medicines (PRIME) and Orphan Medicinal Product designations, to
apitegromab for the treatment of SMA. The efficacy and safety of
apitegromab have not been established and apitegromab has not been
approved for any use by the FDA or any other regulatory agency.
About SMA
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 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, via SMN-dependent pathways, there
continues to be a high unmet need for therapeutics that directly
address muscle function.
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, and
fibrosis. Scholar Rock’s approach to targeting 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/). Investors and
others should note that we communicate with our investors and the
public using our company website www.scholarrock.com, including,
but not limited to, company disclosures, investor presentations and
FAQs, Securities and Exchange Commission filings, press releases,
public conference call transcripts and webcast transcripts, as well
as on Twitter and LinkedIn. The information that we post on our
website or on Twitter or LinkedIn could be deemed to be material
information. As a result, we encourage investors, the media and
others interested to review the information that we post there on a
regular basis. The contents of our website or social media shall
not be deemed incorporated by reference in any filing under the
Securities Act of 1933, as amended.
Scholar Rock® is a registered trademark of Scholar Rock,
Inc.
Forward-Looking Statements
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 its growth,
strategy, progress and timing of its clinical trials for
apitegromab, and other product candidates and indication selection
and development timing, the ability of any product candidate to
perform in humans in a manner consistent with earlier nonclinical,
preclinical or clinical trial data, and the potential of its
product candidates and proprietary platform. The use of words such
as “may,” “might,” “could,” “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,
without limitation, that preclinical and clinical data, including
the results from the Phase 2 clinical trial, including extension
periods, of apitegromab are not predictive of, may be inconsistent
with, or more favorable than, data generated from future clinical
trials of the same product candidate, including, without
limitation, the Phase 3 clinical trial of apitegromab in SMA,
Scholar Rock’s ability to provide the financial support, resources
and expertise necessary to identify and develop product candidates
on the expected timeline, the data generated from Scholar Rock’s
nonclinical and preclinical studies and clinical trials,
information provided or decisions made by regulatory authorities,
competition from third parties that are developing products for
similar uses, Scholar Rock’s ability to obtain, maintain and
protect its intellectual property, Scholar Rock’s dependence on
third parties for development and manufacture of product candidates
including, without limitation, to supply any clinical trials,
Scholar Rock’s ability to manage expenses and to obtain additional
funding when needed to support its business activities and
establish and maintain strategic business alliances and new
business initiatives, and the impacts of public health pandemics
such as COVID-19 on business operations and expectations, as well
as 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, 2022, 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.
1 Dunaway Young, Sally et al. ‘Scoliosis Surgery Significantly
Impacts Motor Abilities in Higher-functioning Individuals with
Spinal Muscular Atrophy’. Journal of Neuromuscular Disease. 1 Jan.
2020: 183–192.
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version on businesswire.com: https://www.businesswire.com/news/home/20220617005087/en/
Scholar Rock:
Investors Rushmie Nofsinger Scholar Rock
rnofsinger@scholarrock.com ir@scholarrock.com 857-259-5573
Media Ariane Lovell Finn Partners
ariane.lovell@finnpartners.com media@scholarrock.com
917-565-2204
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