Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision
genetic medicine for rare diseases, today announced results from
the ongoing MOMENTUM study (Study 5051-201), a global Phase 2
clinical trial, of SRP-5051, its next-generation treatment for
patients with Duchenne muscular dystrophy who are amenable to exon
51 skipping. This is the first clinical data from SRP-5051, an
investigational treatment that uses Sarepta’s peptide
phosphorodiamidate morpholino oligomer (PPMO) technology. PPMO
technology includes a proprietary cell-penetrating peptide that is
conjugated to Sarepta’s PMO backbone with the goal of increasing
cellular uptake of drug in the muscle tissue.
Results from Part A of the multi-ascending dose
MOMENTUM study found consistently higher tissue exposure,
exon-skipping and dystrophin production in patients taking a
monthly dose of SRP-5051 compared to baseline. SRP-5051 was
generally well-tolerated across all doses studied, with no clinical
or laboratory findings reported. The results support continued dose
escalation of SRP-5051 and further clinical development.
“Sarepta’s PMO RNA technology is a vital
platform on which we design therapies to treat those with Duchenne
muscular dystrophy. Our next-generation PPMO technology is designed
to increase cell penetration with the goal of offering
significantly improved efficacy with more convenient dosing in
Duchenne patients amenable to exon skipping,” said Doug Ingram,
president and chief executive officer, Sarepta. “While patient
numbers in each dose arm are small, the higher tissue
concentration, exon skipping and dystrophin production in the 20
mg/kg dosing group were observed at an early 12-week timepoint and
with far less cumulative drug exposure when compared to our current
PMO technology. We know from our experience with PMOs that
exon-skipping and dystrophin increase over time, and these results
along with our preclinical experience, give us confidence as we
dose escalate and continue to advance our PPMO exon-skipping
therapies for Duchenne, including another five potential therapies
that have already been designed, and explore the utility of the
PPMO RNA platform for new disease indications.”
When compared to a control group of Duchenne
patients from the PROMOVI study who received biopsies at 24 weeks
after taking a weekly 30 mg/kg dose of eteplirsen, once-monthly
dosing of SRP-5051 resulted in higher muscle concentration,
increased exon-skipping and dystrophin at 12 weeks. A
dose-dependent increase in exon-skipping and dystrophin was
observed, with patients in the 20 mg/kg dose group of SRP-5051
seeing a 1.6-fold increase in exon skipping (n=4) and a 5-fold
increase in the % of normal dystrophin (n=2) when compared to the
group taking eteplirsen at 24 weeks.
The incidence of adverse events in the MOMENTUM
study was similar across all dosed cohorts and does not suggest
dose dependency. One treatment-emergent event, unrelated to study
drug, occurred in the 4 mg/kg dose group. No clinical or laboratory
findings were observed. Full results will be presented at a future
medical meeting.
About MOMENTUM
(SRP-5051-201) MOMENTUM is a multi-arm, ascending dose
study designed to identify the maximum tolerated dose of SRP-5051.
Informed by Study 5051-101, a single-ascending dose study of
SRP-5051, patients in the MOMENTUM study will receive monthly
intravenous (IV) infusions of SRP-5051, starting at 4 mg/kg and
ascending to 40 mg/kg. The study will enroll up to 24 patients,
both ambulant and non-ambulant, between the ages of 7 to 21 at
sites in the U.S., Canada, Australia and European Union. The
primary endpoint is safety, and secondary and exploratory endpoints
include exon-skipping, dystrophin expression and tissue
concentration. All patients will undergo a muscle biopsy at
baseline and 12 weeks in Part A and at baseline and 24 weeks in
Part B. More information can be found on
www.clinicaltrials.gov.
About SRP-5051SRP-5051 uses
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 truncated 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 DMD patients have mutations which make
them amenable to skipping exon 51. If successful, the PPMO offers
the potential for improved efficacy and less frequent dosing for
patients.
About Duchenne Muscular
DystrophyDMD is an X-linked rare degenerative
neuromuscular disorder causing severe progressive muscle loss and
premature death. One of the most common fatal genetic disorders,
DMD affects approximately one in every 3,500 - 5,000 male births
worldwide. A devastating and incurable muscle-wasting disease, DMD
is associated with specific errors in the gene that codes for
dystrophin, a protein that plays a key structural role in muscle
fiber function. Progressive muscle weakness in the lower limbs
spreads to the arms, neck and other areas of the body. The
condition is universally fatal, and death usually occurs before the
age of 30 due to respiratory or cardiac failure.
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 “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 DMD 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 51Hypersensitivity reactions, including rash and
urticaria, pyrexia, flushing, cough, dyspnea, bronchospasm, and
hypotension, 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 DMD 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.
In the 88 patients who received ≥30 mg/kg/week
of EXONDYS 51 for up to 208 weeks in clinical studies, the
following events were reported in ≥10% of patients and occurred
more frequently than on the same dose in Study 1: vomiting,
contusion, excoriation, arthralgia, rash, catheter site pain, and
upper respiratory tract infection.
For further information, please see the
full Prescribing Information.
About Sarepta
TherapeuticsAt Sarepta, we are leading a revolution in
precision genetic medicine and every day is an opportunity to
change the lives of people living with rare disease. The Company
has built an impressive position in Duchenne muscular dystrophy
(DMD) and in gene therapies for limb-girdle muscular dystrophies
(LGMDs), mucopolysaccharidosis type IIIA, Charcot-Marie-Tooth
(CMT), and other CNS-related disorders, with more than 40 programs
in various stages of development. The Company’s programs and
research focus span several therapeutic modalities, including RNA,
gene therapy and gene editing. For more information, please
visit www.sarepta.com or follow us on Twitter, LinkedIn,
Instagram and Facebook.
Forward-Looking StatementsThis
press release contains "forward-looking statements." 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," "intends," "potential," "possible" and similar expressions
are intended to identify forward-looking statements. These
forward-looking statements include statements regarding the
potential benefits of PPMO, including increasing cellular uptake of
drug in the muscle tissue and offering significantly improved
efficacy with less frequent dosing; our plan to continue to dose
escalate and advance our PPMO exon-skipping therapies for Duchenne,
including another five potential therapies that have already been
designed, and to explore the utility of the PPMO RNA platform for
new disease indications; and potential market opportunities.
These forward-looking statements involve risks
and uncertainties, many of which are beyond our control. Known risk
factors include, among others: success in preclinical trials and
clinical trials, especially if based on a small patient sample,
does not ensure that later clinical trials will be successful; the
data presented in this release may not be consistent with the final
data set and analysis thereof or result in a safe or effective
treatment benefit; different methodologies, assumptions and
applications we utilize 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 foreign regulatory authorities; if
the actual number of patients suffering from DMD is smaller than
estimated, our revenue and ability to achieve profitability may be
adversely affected; we may not be able to execute on our business
plans and goals, including meeting our expected or planned
regulatory milestones and timelines, clinical development plans,
and bringing our product candidates to market, due to a variety of
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, 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 the
COVID-19 pandemic; and even if Sarepta’s programs result in new
commercialized products, Sarepta may not achieve the expected
revenues from the sale of such products; and those risks identified
under the heading “Risk Factors” in Sarepta’s most recent Annual
Report on Form 10-K for the year ended December 31, 2019, and 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.
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.
Internet Posting of
InformationWe 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.
Source: Sarepta Therapeutics, Inc.
Sarepta Therapeutics, Inc.
Investors:Ian Estepan, 617-274-4052, iestepan@sarepta.com
Media:Tracy Sorrentino,
617-301-8566, tsorrentino@sarepta.com
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