- At target dose (~30 mg/kg), SRP-5051 dosed monthly resulted
in mean dystrophin expression of 5.17% and mean exon skipping of
11.11% at 28 weeks (n=20)
- The data support a positive benefit-risk profile for
SRP-5051
- Sarepta will host a conference call at 8:30 a.m. Eastern
time on Jan. 29, 2024
Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in
precision genetic medicine for rare diseases, today announced
positive data from Part B of the MOMENTUM study (Study
SRP-5051-201), a global, Phase 2, multi-ascending dose clinical
trial of SRP-5051 (vesleteplirsen) that enrolled patients aged 8 to
21 years. SRP-5051 is a next-generation peptide phosphorodiamidate
morpholino oligomer (PPMO) treatment for patients with Duchenne
muscular dystrophy who are amenable to exon 51 skipping.
Data from Part B of MOMENTUM found that at the higher, target
dose, approximately 30 mg/kg dosed every four weeks, SRP-5051
resulted in mean dystrophin expression of 5.17%, and mean exon
skipping of 11.11% at 28 weeks (n=20). Consistent dystrophin
expression was seen in ambulatory (4.76%, n=11) and non-ambulatory
(5.67%, n=9) participants at 28 weeks. Hypomagnesemia has
previously been identified in patients taking SRP-5051 and was
managed and monitored through prophylactic magnesium
supplementation as part of the study protocol.
“SRP-5051 dosed every four weeks is showing substantially higher
increases in dystrophin and exon skipping compared to eteplirsen
dosed weekly,” said Louise Rodino-Klapac, Ph.D., executive vice
president, chief scientific officer and head of research and
development, Sarepta Therapeutics. “The data suggest a favorable
benefit-risk profile for SRP-5051 and we look forward to discussing
the results and next steps with FDA. As the leader in Duchenne,
Sarepta is committed to advancing meaningful treatments for those
with Duchenne and other rare diseases where there is unmet
need.”
High dose results at 28 weeks (~30 mg/kg, dosed every four
weeks, n=20):
- 5.17% mean dystrophin expression as measured by western
blot
- 4.53% mean change from baseline, P < 0.0001
- Mean exon skipping of 11.11%, as measured by digital drop
polymerase chain reaction (ddPCR), and a mean change from baseline
in exon skipping of 10.07%
- The changes from baseline represent a 12.2-fold increase in
dystrophin expression and a 24.6-fold increase in exon skipping
compared to a weekly 30 mg/kg dose of eteplirsen at 24 weeks (mean
dystrophin expression of 0.82%, mean exon skipping of 0.59%,
n=16).
Low dose results at 28 weeks (~20 mg/kg, dosed every four weeks,
n=20):
- 2.81% mean dystrophin expression as measured by western
blot
- 1.60% mean change from baseline, P= 0.0012
- Mean exon skipping of 2.47%, as measured by ddPCR, and a mean
change from baseline in exon skipping of 2.00%
- The changes from baseline represent a 4.3-fold increase in
dystrophin expression and a 4.9-fold increase in exon skipping
compared to a weekly 30 mg/kg dose of eteplirsen at 24 weeks.
“The dystrophin production delivered by SRP-5051 in the MOMENTUM
study is very encouraging. Importantly, with effective
supplementation and monitoring, we have not seen additional
complications from the hypomagnesemia,” said Eugenio Mercuri, M.D.,
Ph.D., head of the Neuromuscular Unit, Catholic University, Rome,
Italy, and an investigator in the study. “The results with SRP-5051
to date suggest it could play an important role in the treatment of
Duchenne patients with a confirmed exon 51-amenable mutation.”
There were seven serious, treatment-emergent adverse events in
MOMENTUM Part B, four serious events of hypomagnesemia and three
serious cases of hypokalemia. Hypomagnesemia has been seen in
earlier clinical studies of SRP-5051 and, throughout MOMENTUM Part
B, supplemental magnesium was administered prophylactically. No
treatment-related discontinuations occurred in the study.
Conference call details
At 8:30 a.m. Eastern time on Jan. 29, 2024, Sarepta will host a
conference call and webcast to discuss the 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 SRP-5051 (vesleteplirsen)
SRP-5051 is an investigational agent using Sarepta’s PPMO
chemistry and exon-skipping technology to skip exon 51 of the
dystrophin gene. SRP-5051 is designed to bind to exon 51 of
dystrophin pre-mRNA, resulting in exclusion of this exon during
mRNA processing in patients with genetic mutations that are
amenable to exon 51 skipping. Exon skipping is intended to allow
for production of an internally shortened dystrophin protein. PPMO
is Sarepta’s next-generation chemistry platform designed around a
proprietary cell-penetrating peptide conjugated to the PMO
backbone, with the goal of increasing tissue penetration,
increasing exon skipping, and significantly increasing dystrophin
production. Around 13% of Duchenne patients have mutations that
make them amenable to skipping exon 51. If successful, the PPMO
offers the potential for improved efficacy and less frequent dosing
for patients.
About MOMENTUM (Study SRP-5051-201)
MOMENTUM is a global, Phase 2, multi-arm, ascending dose study
of SRP-5051, infused every four weeks, and will assess dystrophin
protein levels in skeletal muscle tissue following SRP-5051
treatment. The study will also assess safety and tolerability. Part
B enrolled 40 participants, both ambulant and non-ambulant, between
the ages of 8 to 21 at sites in the U.S., Canada, and Europe.
More information can be found on www.clinicaltrials.gov.
About EXONDYS 51
EXONDYS 51 (eteplirsen) uses Sarepta’s proprietary
phosphorodiamidate morpholino oligomer (PMO) chemistry and
exon-skipping technology to bind to exon 51 of dystrophin pre-mRNA,
resulting in exclusion, or “skipping”, of this exon during mRNA
processing in patients with genetic mutations that are amenable to
exon 51 skipping. Exon skipping is intended to allow for production
of an internally truncated dystrophin protein.
EXONDYS 51 is indicated for the treatment of Duchenne muscular
dystrophy in patients who have a confirmed mutation of the
dystrophin gene that is amenable to exon 51 skipping.
This indication is approved under accelerated approval based on
an increase in dystrophin production in skeletal muscle observed in
some patients treated with EXONDYS 51. Continued approval may be
contingent upon verification of a clinical benefit in confirmatory
trials.
EXONDYS 51 has met the full statutory standards for safety and
effectiveness and as such is not considered investigational or
experimental.
Important Safety Information About EXONDYS 51
Hypersensitivity reactions, bronchospasm, chest pain, cough,
tachycardia, and urticaria have occurred in patients who were
treated with EXONDYS 51. If a hypersensitivity reaction occurs,
institute appropriate medical treatment and consider slowing the
infusion or interrupting the EXONDYS 51 therapy.
Adverse reactions in Duchenne patients (N=8) treated with
EXONDYS 51 30 mg or 50 mg/kg/week by intravenous (IV) infusion with
an incidence of at least 25% more than placebo (N=4) (Study 1, 24
weeks) were (EXONDYS 51, placebo): balance disorder (38%, 0%),
vomiting (38%, 0%) and contact dermatitis (25%, 0%). The most
common adverse reactions were balance disorder and vomiting.
Because of the small numbers of patients, these represent crude
frequencies that may not reflect the frequencies observed in
practice. The 50 mg/kg once weekly dosing regimen of EXONDYS 51 is
not recommended.
The following adverse reactions have been identified during
observational studies that were conducted as part of the clinical
development program and continued post approval.
In open-label observational studies, 163 patients received at
least one intravenous dose of EXONDYS 51, with doses ranging
between 0.5 mg/kg (0.017 times the recommended dosage) and 50 mg/kg
(1.7 times the recommended dosage). All patients were male and had
genetically confirmed Duchenne muscular dystrophy. Age at study
entry was 6 months to 19 years. Most (85%) patients were
Caucasian.
The most common adverse reactions from observational clinical
studies (N=163) seen in greater than 10% of the study population
were headache, cough, rash, and vomiting.
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
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 our future operations, financial
performance and projections, business plans, market opportunities,
priorities and research and development programs and technologies;
the potential benefits of our technologies and scientific
approaches; the potential benefits of SRP-5051, including its
potential for higher dystrophin and exon-skipping than eteplirsen
and a favorable benefit-risk profile, including that hypomagnesemia
is manageable; and plans and milestones, including discussing
results and next steps with FDA.
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
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 may fail to meet
regulatory approval requirements for the safety and efficacy of
product candidates; certain programs may never advance in the
clinic or may be discontinued for a number of reasons, including
regulators imposing a clinical hold and us suspending or
terminating clinical research or trials; if the actual number of
patients suffering from the diseases we aim to treat is smaller
than estimated, our revenue and ability to achieve profitability
may be adversely affected; because we are developing product
candidates for the treatment of certain diseases in which there is
little clinical experience and we are using new endpoints or
methodologies, there is increased risk that the FDA, the EMA or
other regulatory authorities may not consider the endpoints of our
clinical trials to provide clinically meaningful results and that
these results may be difficult to analyze; 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, 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 Annual Report on Form 10-K for the year
ended December 31, 2022 and 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20240129970075/en/
Investor: Ian Estepan, 617-274-4052
iestepan@sarepta.com
Media: Tracy Sorrentino, 617-301-8566
tsorrentino@sarepta.com
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