– Results support submission of an efficacy supplement to the
BLA; US FDA has indicated openness to reviewing the data for label
expansion based on the totality of evidence from EMBARK
– In EMBARK, participants treated with ELEVIDYS
(delandistrogene moxeparvovec-rokl) showed an increase on the North
Star Ambulatory Assessment, a measure of motor function, compared
to placebo-treated patients at 52 weeks, although the primary
endpoint was not met
– Robust, statistically significant results on all key
pre-specified secondary endpoints, including time to rise
(p=0.0025), and 10-meter walk test (p=0.0048), demonstrated
evidence of a clinically meaningful treatment benefit that was
similar in magnitude and statistical significance across all age
groups
– No new safety signals were observed
– Sarepta to host investor call on October 30 at 4:30 p.m.
Eastern time
Sarepta Therapeutics, Inc. (NASDAQ: SRPT), the leader in
precision genetic medicine for rare diseases, today announced
topline results from EMBARK (Study SRP-9001-301), a global,
randomized, double-blind, placebo-controlled, Phase 3 clinical
study of ELEVIDYS (delandistrogene moxeparvovec-rokl) in patients
with Duchenne muscular dystrophy between the ages of 4 through 7
years.
“The results of EMBARK, our double-blind, placebo-controlled
trial, support the conclusion that ELEVIDYS modifies the trajectory
of Duchenne and benefits patients across age groups living with
this ferociously degenerative disease. The results favored ELEVIDYS
across all endpoints in the study, including achieving statistical
significance on all pre-specified key secondary endpoints and in
each age subgroup of the key secondary endpoints. Indeed, passing 5
seconds on time to rise is the strongest predictor of early loss of
ambulation and in EMBARK, ELEVIDYS reduced those odds over 52 weeks
by greater than 90 percent,” said Doug Ingram, president and chief
executive officer, Sarepta. “Based on the EMBARK results, we intend
to move swiftly to request an update to expand the labeled
indication to treat all patients. Importantly, we have shared the
EMBARK topline results with FDA leadership and they have confirmed
that, based on the totality of the evidence, they are open to such
label expansion if supported by review of the data, and that they
intend to proceed rapidly with consideration of the
submission.”
In the study, ELEVIDYS-treated patients improved 2.6 points on
their North Star Ambulatory Assessment (NSAA) total score 52 weeks
after treatment compared to 1.9 points in placebo-treated patients.
The difference of 0.65-points between treated and placebo groups
did not reach statistical significance (n=125; p=0.24).
All key pre-specified functional secondary endpoints
demonstrated robust evidence for a clinically meaningful treatment
benefit that was consistent across age groups in ELEVIDYS-treated
patients compared to placebo at 52 weeks. These include:
Time to rise (TTR)
Change vs Placebo LSM* Diff in
Seconds
Overall (n=124)
-0.64 (p=0.0025)
Ages 4-5 (n=59)
-0.50 (p=0.0177)
Ages 6-7 (n=65)
-0.78 (p=0.0291)
10-meter walk test
Change vs Placebo LSM Diff in
Seconds
Overall (n=124)
-0.42 (p=0.0048)
Ages 4-5 (n=59)
-0.33 (p=0.0319)
Ages 6-7 (n=65)
-0.52 (p=0.0363)
*least squared means
All other timed functional endpoints – including stride velocity
95th centile (SV95C) and time to ascend 4 steps – demonstrated
consistent treatment benefit in favor of ELEVIDYS. Full results
from EMBARK will be shared at future medical meetings and
publication will be pursued in a medical journal.
“The strong prognostic power of time to rise, and the particular
importance of the 5 second milestone in predicting functional
decline and future loss of ambulation, is clearly demonstrated in
natural history.1 In EMBARK, the reduction in patients progressing
past this milestone when treated with ELEVIDYS is highly clinically
relevant,” 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. “The consistency of the
positive effect across all timed function tests and age groups
provides evidence of a meaningful treatment effect. In addition, it
is important to note that this is the first clinical trial in the
history of DMD trials to show a statistically significant and
meaningful improvement on the novel measure of 95th centile stride
velocity derived from an objective community wearable activity
monitor.”
There were no new safety signals in the EMBARK study,
reinforcing the favorable and manageable safety profile observed
with ELEVIDYS to date. The most common treatment-related adverse
events were gastrointestinal events (vomiting, nausea, and
decreased appetite) and pyrexia. Seven participants (11.1%)
experienced a treatment-related serious adverse event (SAE) and
there were no clinically meaningful changes observed in SAEs
associated with known risks of ELEVIDYS.
Conference call details
On October 30, 2023, at 4:30 p.m. Eastern time, 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.
As part of a collaboration agreement signed in 2019, Roche is
working with Sarepta Therapeutics to transform the future for the
Duchenne community, enabling those living with the disease to
maintain and protect their muscle function, keeping them stronger
for longer. 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.
Together, the companies are implementing a comprehensive joint
clinical development plan to maximize the chances of broad approval
and access so that ELEVIDYS can reach as many individuals with
Duchenne as rapidly as possible.
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 remain blinded.
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.
About ELEVIDYS (delandistrogene moxeparvovec-rokl)
ELEVIDYS (delandistrogene moxeparvovec-rokl) is a single-dose
gene transfer therapy for intravenous infusion designed to address
the underlying cause of Duchenne muscular dystrophy through the
targeted production of ELEVIDYS micro-dystrophin in skeletal
muscle. ELEVIDYS is indicated for the treatment of ambulatory
pediatric patients aged 4 through 5 years with Duchenne muscular
dystrophy (DMD) with a confirmed mutation in the DMD gene and is
approved under accelerated approval based on expression of ELEVIDYS
micro-dystrophin in skeletal muscle observed in patients treated
with ELEVIDYS. Continued approval for this indication may be
contingent upon verification of a clinical benefit in confirmatory
trials. ELEVIDYS has met the full statutory standards for safety
and effectiveness and as such is not considered investigational or
experimental.
In addition to EMBARK, which serves as the postmarketing
confirmatory study, ELEVIDYS has been evaluated in three ongoing
clinical studies: SRP-9001-101, SRP-9001-102 and SRP-9001-103.
Accelerated approval was primarily based on data from SRP-9001-102
and SRP-9001-103.
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:
Acute Serious Liver Injury:
- Acute serious liver injury has been observed with ELEVIDYS.
Administration of ELEVIDYS may result in elevations of liver
enzymes (e.g., 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, a
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 between exons 1 to 17 and 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.
- 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.
Pre-existing 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 subjects developed
anti-AAVrh74 antibodies.
- Perform baseline testing for the 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 function test
increased, pyrexia, and thrombocytopenia.
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 Twitter, LinkedIn, 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
This press release contains “forward-looking statements.” Any
statements that are not statements of historical fact may be deemed
to be forward-looking statements. Words such as “believe,”
“anticipate,” “plan,” “expect,” “will,” “may,” “intend,” “prepare,”
“look,” “potential,” “possible” and similar expressions are
intended to identify forward-looking statements. These
forward-looking statements include, without limitation, statements
relating to our future operations, business plans, priorities,
research and development programs; our understanding that U.S. FDA
has indicated openness to reviewing the data for label expansion
based on the totality of evidence from EMBARK, if supported by
review of the data, and that they intend to proceed rapidly with
consideration of the submission; the potential benefits of
ELEVIDYS, including the potential to modify the trajectory of
Duchenne and benefit patients across age groups living with
Duchenne; and expected plans and milestones, including moving
swiftly to request an update to expand the labeled indication to
treat all patients for ELEVIDYS, and sharing full results from
EMBARK at future medical meetings and a publication pursued in a
medical journal.
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:
the FDA may not approve a supplement to expand the approved label
for ELEVIDYS; we may not be able to comply with all FDA requests in
a timely manner or at all; the possible impact of regulations and
regulatory decisions by the FDA and other regulatory agencies on
our business; our data may not be sufficient for obtaining
regulatory approval; we are subject to uncertainty related to
reimbursement policies; success in preclinical and clinical trials,
especially if based on a small patient sample, does not ensure that
later clinical trials will be successful, and the results of future
research may not be consistent with past positive results or with
advisory committee recommendations, or may fail to meet regulatory
approval requirements for the safety and efficacy of product
candidates; continued approval may be contingent upon verification
of a clinical benefit in confirmatory trials; the commencement and
completion of our clinical trials and announcement of results may
be delayed or prevented for a number of reasons, including, among
others, denial by the regulatory agencies of permission to proceed
with our clinical trials, or placement of a clinical trial on hold,
challenges in identifying, recruiting, enrolling and retaining
patients to participate in clinical trials and inadequate quantity
or quality of supplies of a product candidate or other materials
necessary to conduct clinical trials; different methodologies,
assumptions and applications we use to assess particular safety or
efficacy parameters may yield different statistical results, and
even if we believe the data collected from clinical trials of our
product candidates are positive, these data may not be sufficient
to support approval by the FDA or other global regulatory
authorities; 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, and bringing
our product candidates to market, for various reasons, many 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,
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 Annual Report on Form
10-K for the year ended December 31, 2022, and 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.
Any of the foregoing risks could materially and adversely affect
the Company’s business, results of operations and the trading price
of Sarepta’s common stock. For a detailed description of risks and
uncertainties Sarepta faces, you are encouraged to review the SEC
filings made by Sarepta. We caution investors not to place
considerable reliance on the forward-looking statements contained
in this press release. Sarepta does not undertake any obligation to
publicly update its forward-looking statements based on events or
circumstances after the date hereof, except as required by law.
Reference: 1) Zambon, AA, et al; The UK Northstar Clinical
Network. Peak functional ability and age at loss of ambulation in
Duchenne muscular dystrophy. Dev Med Child Neurol. 2022; 64:
979–988.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20231030875867/en/
Investors: Ian Estepan, 617-274-4052
iestepan@sarepta.com
Media: Tracy Sorrentino, 617-301-8566
tsorrentino@sarepta.com
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