– Treatment with ELEVIDYS corresponded with increases on the
North Star Ambulatory Assessment (NSAA) at one year in crossover
patients, while the study remained blinded
– MRI results at two years in patients treated in Part 1 show
minimal muscle pathology progression, aligning closely with
observed functional benefits
– Crossover-treated patients show statistically significant
benefits of ELEVIDYS treatment on NSAA, Time to Rise (TTR), and
10-meter walk/run (10MWR), when compared to a pre-specified,
well-matched external control (EC)
– Part 1-treated patients show sustained expression at week
64, and functional improvements on NSAA, TTR and 10MWR were
sustained two years after treatment and show a widening divergence
compared to EC
– Safety remained consistent with the profile of ELEVIDYS
already established across a broad Duchenne population
– Investor webcast to be held today at 8:30 a.m. ET
Sarepta Therapeutics, Inc. (NASDAQ: SRPT), the leader in
precision genetic medicine for rare diseases, today announced
positive topline results from Part 2 of EMBARK (Study
SRP-9001-301), a global, randomized, double-blind,
placebo-controlled, Phase 3 clinical study of ELEVIDYS
(delandistrogene moxeparvovec-rokl), the only approved gene therapy
in patients with Duchenne muscular dystrophy.
Crossover-treated patients, those who received a placebo in Part
1 and crossed over at 52 weeks and were treated with ELEVIDYS in
Part 2, improved 2.34 points from baseline compared to matched
external controls on the North Star Ambulatory Assessment (NSAA) 52
weeks after treatment (P<0.0001), during which time the study
remained blinded.
Despite being one year older (average age 7.18 years) than those
treated in Part 1 (average age 5.98 years), crossover-treated
patients showed clinically meaningful and statistically significant
functional benefit for NSAA, Time to Rise (TTR), and 10-meter
walk/run (10MWR) function tests compared with a pre-specified,
propensity-weighted external control group* (EC).
Crossover-Treated Patients (n=59) vs. EC
Functional Outcomes
LSM
P-Value
NSAA
+2.34 points
P<0.0001
TTR
-2.70 seconds (improvement)
P<0.0001
10MWR
-1.07 seconds (improvement)
P=0.0001
Two-Year Results
In patients treated in Part 1, biopsies taken 64 weeks after
dosing showed consistent and sustained expression of ELEVIDYS
micro-dystrophin compared to week 12 biopsies, as measured by
western blot, and provide biological support for observed
functional outcomes.
At two years, patients treated in Part 1 of EMBARK showed
clinically meaningful and statistically significant functional
benefit in NSAA, TTR and 10MWR compared with EC. Furthermore, the
least square means (LSM) differences seen between the patients
treated in Part 1 and the EC group increase from year one to year
two for all three functional outcomes. This indicates that the
trajectory of disease in patients treated with ELEVIDYS is
continuing to diverge from the natural history of DMD.
Part 1, Year 2 (n=63) ELEVIDYS-Treated vs. EC
Functional Outcomes
LSM
P-Value
NSAA
+2.88 points
P=0.0001
TTR
-2.06 seconds (improvement)
P=0.0033
10MWR
-1.36 seconds (improvement)
P=0.0028
Skeletal muscle MRI conducted on patients treated in Part 1
found minimal progression in underlying muscle pathology and remain
highly consistent with the functional benefits shown.
“We’re very encouraged to see the results from Part 2 of EMBARK
as they further elucidate the impact ELEVIDYS has on disease
progression in a blinded, controlled study. Skeletal muscle MRI
demonstrates the importance of preserving muscle, and the
functional outcome results show disease stabilization sustained
through two years after treatment,” said Louise Rodino-Klapac,
Ph.D., executive vice president, Head of R&D, Chief Scientific
Officer. “Over time, we continue to observe a statistically
significant difference favoring ELEVIDYS compared to a well-matched
external control on NSAA and timed tests. The consistency and
totality of evidence supporting a long-term and clinically
meaningful treatment benefit with ELEVIDYS continues to grow. We
look forward to sharing more details with the clinical community in
upcoming scientific forums.”
No new safety signals were observed, reinforcing the consistent
and manageable safety profile of ELEVIDYS to date. Detailed results
from Part 2 of the EMBARK study will be shared at future medical
meetings.
“As a neuromuscular medicine specialist who has seen patients
with Duchenne muscular dystrophy for over three decades, I’ve
witnessed firsthand the positive impact of gene therapy on the
trajectory of Duchenne,” said Craig McDonald, M.D., professor and
chair of the UC Davis Health Department of Physical Medicine and
Rehabilitation, and an investigator in the EMBARK study. “These
longer-term results are even more striking when compared to
external control given the progressive nature of the disease, and
we’d expect to see this divergence grow over time. The efficacy of
ELEVIDYS gives me great hope as we continue to follow these
patients and see others treated in the clinical setting.”
As part of a collaboration agreement signed in 2019, Sarepta is
working with Roche to transform the future for the Duchenne
community, enabling those living with the disease to maintain and
protect their muscle function. Sarepta is responsible for
regulatory approval and commercialization of ELEVIDYS in the U.S.,
as well as manufacturing. Roche is responsible for regulatory
approvals and bringing ELEVIDYS to patients across the rest of the
world.
ELEVIDYS is approved for people living with Duchenne aged four
years old and over regardless of their ambulatory status in the
U.S., United Arab Emirates (UAE), Qatar, Kuwait, Bahrain and Oman.
ELEVIDYS is also approved for the treatment of ambulatory patients
aged four through seven years in Brazil and Israel.
*The pre-specified external control used data from five separate
studies in Duchenne, comprising DMD controls from two randomized
trials and three natural history cohorts who met predefined
matching criteria. Comparison of treated and control patients was
based on a pre-specified, propensity score weighting approach using
age, steroid usage, baseline NSAA and timed function tests in order
to balance key prognostic factors between the groups.
Sarepta Investor Call Details
At 8:30 a.m. ET on Jan. 27, 2025, Sarepta will host a conference
call and webcast to discuss these results.
The event will be webcast live under the investor relations
section of Sarepta’s website at
https://investorrelations.sarepta.com/events-presentations and
following the event a replay will be archived there for one year.
Interested parties participating by phone will need to register
using this online form. After registering for dial-in details, all
phone participants will receive an auto-generated e-mail containing
a link to the dial-in number along with a personal PIN number to
use to access the event by phone.
About EMBARK, Study 9001-301
Study SRP-9001-301, also known as EMBARK, is a multinational,
phase 3, randomized, two-part crossover, placebo-controlled study
of ELEVIDYS in individuals with Duchenne muscular dystrophy between
the ages of 4 to 7 years. The primary endpoint is change from
baseline in NSAA Total Score at Week 52 following treatment.
Eligible participants received a single dose of ELEVIDYS during
either Part 1 or Part 2 of the study.
In Part 1, participants (n=125) were randomized according to age
(≥4 to <8 years) or NSAA Total Score at screening (>16 to
<29) and received either 1.33 x1014 vg/kg of ELEVIDYS or placebo
with a follow-up period for 52 weeks. In Part 2, participants cross
over - meaning, those who were previously treated with placebo in
Part 1 receive ELEVIDYS and participants who were previously
treated with ELEVIDYS receive placebo, with a follow-up period for
52 weeks. All patients remained blinded through Part 1 and Part
2.
Secondary outcome measures in EMBARK include the quantity of
shortened dystrophin produced by ELEVIDYS at week 12 as measured by
western blot in a subset of participants, timed function tests,
stride velocity and validated patient reported outcome measures for
mobility and upper limb function. One-year results from the Part 1
placebo-controlled period of the EMBARK study were published in
Nature Medicine in October 2024.
About ELEVIDYS (delandistrogene moxeparvovec-rokl)
ELEVIDYS (delandistrogene moxeparvovec-rokl) is a single-dose,
adeno-associated virus (AAV)-based gene transfer therapy for
intravenous infusion designed to address the underlying genetic
cause of Duchenne muscular dystrophy – mutations or changes in the
DMD gene that result in the lack of dystrophin protein – through
the delivery of a transgene that codes for the targeted production
of ELEVIDYS micro-dystrophin in skeletal muscle.
ELEVIDYS is indicated for the treatment of Duchenne muscular
dystrophy (DMD) in individuals at least 4 years of age.
- For patients who are ambulatory and have a confirmed mutation
in the DMD gene
- For patients who are non-ambulatory and have a confirmed
mutation in the DMD gene.
The DMD indication in non-ambulatory patients is approved under
accelerated approval based on expression of ELEVIDYS
micro-dystrophin (noted hereafter as “micro-dystrophin”) in
skeletal muscle. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in
a confirmatory trial(s).
IMPORTANT SAFETY INFORMATION
CONTRAINDICATION: ELEVIDYS is contraindicated in patients with
any deletion in exon 8 and/or exon 9 in the DMD gene.
WARNINGS AND PRECAUTIONS:
Infusion-related Reactions:
- Infusion-related reactions, including hypersensitivity
reactions and anaphylaxis, have occurred during or up to several
hours following ELEVIDYS administration. Closely monitor patients
during administration and for at least 3 hours after the end of
infusion. If symptoms of infusion-related reactions occur, slow, or
stop the infusion and give appropriate treatment. Once symptoms
resolve, the infusion may be restarted at a lower rate.
- ELEVIDYS should be administered in a setting where treatment
for infusion-related reactions is immediately available.
- Discontinue infusion for anaphylaxis.
Acute Serious Liver Injury:
- Acute serious liver injury has been observed with ELEVIDYS, and
administration may result in elevations of liver enzymes (such as
GGT, GLDH, ALT, AST) or total bilirubin, typically seen within 8
weeks.
- Patients with preexisting liver impairment, chronic hepatic
condition, or acute liver disease (e.g., acute hepatic viral
infection) may be at higher risk of acute serious liver injury.
Postpone ELEVIDYS administration in patients with acute liver
disease until resolved or controlled.
- Prior to ELEVIDYS administration, perform liver enzyme test and
monitor liver function (clinical exam, GGT, and total bilirubin)
weekly for the first 3 months following ELEVIDYS infusion. Continue
monitoring if clinically indicated, until results are unremarkable
(normal clinical exam, GGT, and total bilirubin levels return to
near baseline levels).
- Systemic corticosteroid treatment is recommended for patients
before and after ELEVIDYS infusion. Adjust corticosteroid regimen
when indicated. If acute serious liver injury is suspected,
consultation with a specialist is recommended.
Immune-mediated Myositis:
- In clinical trials, immune-mediated myositis has been observed
approximately 1 month following ELEVIDYS infusion in patients with
deletion mutations involving exon 8 and/or exon 9 in the DMD gene.
Symptoms of severe muscle weakness, including dysphagia, dyspnea,
and hypophonia, were observed.
- Limited data are available for ELEVIDYS treatment in patients
with mutations in the DMD gene in exons 1 to 17 and/or exons 59 to
71. Patients with deletions in these regions may be at risk for a
severe immune-mediated myositis reaction.
- Advise patients to contact a physician immediately if they
experience any unexplained increased muscle pain, tenderness, or
weakness, including dysphagia, dyspnea, or hypophonia, as these may
be symptoms of myositis. Consider additional immunomodulatory
treatment (immunosuppressants [e.g., calcineurin-inhibitor] in
addition to corticosteroids) based on patient’s clinical
presentation and medical history if these symptoms occur.
Myocarditis:
- Acute serious myocarditis and troponin-I elevations have been
observed following ELEVIDYS infusion in clinical trials.
- If a patient experiences myocarditis, those with pre-existing
left ventricle ejection fraction (LVEF) impairment may be at higher
risk of adverse outcomes. Monitor troponin-I before ELEVIDYS
infusion and weekly for the first month following infusion and
continue monitoring if clinically indicated. More frequent
monitoring may be warranted in the presence of cardiac symptoms,
such as chest pain or shortness of breath.
- Advise patients to contact a physician immediately if they
experience cardiac symptoms.
Preexisting Immunity against AAVrh74:
- In AAV-vector based gene therapies, preexisting anti-AAV
antibodies may impede transgene expression at desired therapeutic
levels. Following treatment with ELEVIDYS, all patients developed
anti-AAVrh74 antibodies.
- Perform baseline testing for presence of anti-AAVrh74 total
binding antibodies prior to ELEVIDYS administration.
- ELEVIDYS administration is not recommended in patients with
elevated anti-AAVrh74 total binding antibody titers greater than or
equal to 1:400.
Adverse Reactions:
- The most common adverse reactions (incidence ≥5%) reported in
clinical studies were vomiting, nausea, liver injury, pyrexia, and
thrombocytopenia.
Report negative side effects of prescription drugs to the FDA.
Visit www.fda.gov/medwatch or call 1-800-FDA-1088. You may also
report side effects to Sarepta Therapeutics at 1-888-SAREPTA
(1-888-727-3782).
For further information, please see the full Prescribing
Information.
About Sarepta Therapeutics
Sarepta is on an urgent mission: engineer precision genetic
medicine for rare diseases that devastate lives and cut futures
short. We hold leadership positions in Duchenne muscular dystrophy
(DMD) and limb-girdle muscular dystrophies (LGMDs), and we
currently have more than 40 programs in various stages of
development. Our vast pipeline is driven by our multi-platform
Precision Genetic Medicine Engine in gene therapy, RNA and gene
editing. For more information, please visit www.sarepta.com or
follow us on LinkedIn, X, Instagram and Facebook.
Internet Posting of Information
We routinely post information that may be important to investors
in the 'For Investors' section of our website at www.sarepta.com.
We encourage investors and potential investors to consult our
website regularly for important information about us.
Forward-Looking Statements
In order to provide Sarepta’s investors with an understanding of
its current results and future prospects, this press release
contains statements that are forward-looking. Any statements
contained in this press release that are not statements of
historical fact may be deemed to be forward-looking statements.
Words such as “believes,” “anticipates,” “plans,” “expects,”
“will,” “may,” “intends,” “prepares,” “looks,” “potential,”
“possible” and similar expressions are intended to identify
forward-looking statements. These forward-looking statements
include statements relating to ELEVIDYS; the potential benefits of
our agreements with strategic partners; and expected milestones and
plans, including sharing more details with the clinical community
in upcoming scientific forums.
These forward-looking statements involve risks and
uncertainties, many of which are beyond Sarepta’s control. Actual
results could materially differ from those stated or implied by
these forward-looking statements as a result of such risks and
uncertainties. Known risk factors include the following: success in
clinical trials does not ensure that later clinical trials will be
successful, and the results of future research may not be
consistent with past positive results; we may not be able to
execute on our business plans, including meeting our expected or
planned regulatory milestones and timelines, research and clinical
development plans for various reasons, some of which may be outside
of our control, including possible limitations of company financial
and other resources, manufacturing limitations that may not be
anticipated or resolved for in a timely manner, and regulatory,
court or agency decisions, such as decisions by the United States
Patent and Trademark Office with respect to patents that cover our
product candidates; and those risks identified under the heading
“Risk Factors” in our most recent Quarterly Report on Form 10-Q
filed with the Securities and Exchange Commission (SEC) as well as
other SEC filings made by the Company which you are encouraged to
review.
About Sarepta Therapeutics
Sarepta is on an urgent mission: engineer precision genetic
medicine for rare diseases that devastate lives and cut futures
short. We hold leadership positions in Duchenne muscular dystrophy
(DMD) and limb-girdle muscular dystrophies (LGMDs), and we
currently have more than 40 programs in various stages of
development. Our vast pipeline is driven by our multi-platform
Precision Genetic Medicine Engine in gene therapy, RNA and gene
editing. For more information, please visit www.sarepta.com or
follow us on LinkedIn, X, Instagram and Facebook.
Internet Posting of Information
We routinely post information that may be important to investors
in the 'For Investors' section of our website at www.sarepta.com.
We encourage investors and potential investors to consult our
website regularly for important information about us.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20250126244525/en/
Investor: Ian Estepan 617-274-4052
iestepan@sarepta.com
Media: Tracy Sorrentino 617-301-8566
tsorrentino@sarepta.com
Kara Hoeger 617-710-3898 khoeger@sarepta.com
Sarepta Therapeutics (NASDAQ:SRPT)
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