Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision
genetic medicine for rare diseases, today announced positive
results from Part A of the MOMENTUM study (Study 5051-201), a
global, Phase 2, multi-ascending dose clinical trial of SRP-5051,
its next-generation peptide phosphorodiamidate morpholino oligomer
(PPMO) treatment for patients with Duchenne muscular dystrophy who
are amenable to exon 51 skipping.
In biopsies taken at a
median of 12 weeks and after only three doses, results from Part A
of MOMENTUM study found that the 30 mg/kg of SRP-5051 dosed monthly
resulted in 18 times the exon skipping and eight times the
dystrophin production as eteplirsen, dosed weekly for 24 weeks.
Exon-skipping and dystrophin production in the 30 mg/kg cohort were
also consistently higher than the 20 mg/kg cohort of MOMENTUM.
Hypomagnesemia was identified in patients taking SRP-5051. Cases
have resolved with magnesium supplementation and an analysis of all
available data indicate that the hypomagnesemia is monitorable and
manageable.
“We are pleased to
report strong, dose-dependent exon-skipping and dystrophin
expression results with monthly dosing of SRP-5051 – in ambulant
and non-ambulant patients. Even at an early timepoint of 12 weeks
and after as few as only three doses, these data confirm the
potential of Sarepta’s next-generation PPMO platform to be a step
order improvement over our current PMO platform, and to profoundly
impact the course of Duchenne. While we saw exceptional expression
after only a few initial doses, our models predict that we will
exceed dystrophin expression levels of 10% of normal or greater
over time with SRP-5051,” said Doug Ingram, president and chief
executive officer, Sarepta. “We are excited to have chosen our
target dose for further development. Part A of MOMENTUM is now
complete and Sarepta will work with great urgency to discuss the
results with regulatory agencies and gain their insights, including
the development path to support an accelerated approval of SRP-5051
in the United States.”
Results from the 30 mg/kg dose
cohort:
- In biopsies taken at a median of
week 12, 30 mg/kg of SRP-5051 dosed monthly resulted in mean
exon skipping of 10.79% (n=4). Exon skipping was measured
by digital drop polymerase chain reaction (ddPCR).
- This correlates to >4x increase
in exon skipping compared to the 20 mg/kg cohort of SRP-5051 at 12
weeks (mean exon skipping of 2.57%, n=2) and an 18x increase in
exon skipping compared to a weekly 30 mg/kg dose of eteplirsen at
24 weeks (mean exon skipping of 0.59%, n=16).
- At a median of week 12, 30 mg/kg of
SRP-5051 resulted in mean dystrophin production of 6.55% of normal.
Dystrophin expression was measured by western blot.
- This is twice the dystrophin
expression compared to the 20 mg/kg cohort at week 12 (mean
expression of 3.06%) and eight times that of the eteplirsen
comparison group (mean expression of 0.82%).
There were three serious, treatment-emergent
adverse events in two patients in the 30 mg/kg cohort, including
two cases of hypomagnesemia. The events were asymptomatic and have
resolved with magnesium supplementation. Markers of kidney function
have generally been normal and not shown any consistent
relationship to the hypomagnesemia.
Predictive modeling for dystrophin accumulation
that includes assumptions of known turnover of dystrophin in the
muscle and an analysis of data generated with the PPMO platform
indicates that SRP-5051 at 30 mg/kg is likely to deliver greater
than 10% dystrophin over time with monthly dosing.
Full results will be presented at a future
medical meeting.
About MOMENTUM
(Study SRP-5051-201) MOMENTUM is a multi-arm, ascending
dose study designed to identify the maximum tolerated dose of
SRP-5051, infused monthly. 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. 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 Dystrophy DMD 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
51EXONDYS 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
TherapeuticsSarepta 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.
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 market opportunities; the
potential benefits of PPMO, including offering greater efficacy
with less frequent dosing, being a step order improvement over our
current PMO platform, and profoundly impacting the course of
Duchenne; our prediction that SRP-5051 at 30 mg/kg will achieve
greater than 10% dystrophin over time with monthly dosing; and our
plans, including to work with great urgency to discuss the results
with regulatory agencies and gain their insights, including the
development path to support an accelerated approval of SRP-5051 in
the United States and to present full results at a future medical
meeting.
These forward-looking
statements involve risks and uncertainties, many of which are
beyond our control. Known risk factors include, among others:
success in preclinical 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, 2020, as well
as other Securities and Exchange Commission (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.
Investor Contact: Ian Estepan,
617-274-4052iestepan@sarepta.com
Media Contact: Tracy
Sorrentino, 617-301-8566tsorrentino@sarepta.com
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