Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision
genetic medicine for rare diseases, today shared new functional
data across multiple studies from the clinical development program
for SRP-9001 (delandistrogene moxeparvovec) for the treatment of
Duchenne muscular dystrophy. SRP-9001 is an investigational gene
therapy for Duchenne being developed in partnership with Roche.
Data are being presented this week at the 17th International
Congress on Neuromuscular Diseases (ICNMD 2022) in Brussels.
Key findings include new, one-year functional
results from Study SRP-9001-103 (ENDEAVOR), which employs
commercially representative SRP-9001 material at the target
commercial dose. Results from Cohort 1 (n=20, ages 4 to 7)
demonstrated a 3.8-point improvement (unadjusted means) and
3.2-point improvement (least squared means) on the North Star
Ambulatory Assessment* (NSAA) 52 weeks after treatment compared to
a propensity-score weighted external control.** Additionally,
across multiple new analyses, discussed below, SRP-9001 treated
patients showed statistically significant and clinically meaningful
benefit versus propensity-matched external controls and results
positively diverge from the natural history of this degenerative
disease over time.
“We are absolutely delighted by these most
recent results. We now have positive results across multiple
studies and multiple time points, including one-, two- and
four-years after treatment, and are very pleased with the
consistent safety profile across more than 80 treated patients,”
said Doug Ingram, president and chief executive officer, Sarepta.
“We are particularly excited about the results of cohort 1 of Study
103, as these results come from our commercially representative
process at our intended commercial dose. We robustly powered our
120-patient Phase 3 study, known as EMBARK, and the results from
Study 103 provide even greater conviction on the powering and
probability of success of EMBARK. Duchenne is a relentlessly
degenerative disease and every day of delay is a day of muscle and
function loss that cannot be recovered. Sarepta and our partner
Roche are dedicated and determined to bring this potentially
transformative gene therapy to patients around the globe as rapidly
as possible.”
“In Study 103, we continue to see statistically
significant improvements in NSAA scores and timed function tests
for SRP-9001-treated patients from baseline and when compared to a
propensity-weighted external control group. With the progressive
nature of this disease, what has been particularly gratifying is
seeing these treatment effects increase over time compared to the
external control, as well as the maintenance of ability in older
patients who would otherwise be declining,” said Louise
Rodino-Klapac, Ph.D., executive vice president and chief scientific
officer, Sarepta. “We’re excited to share these data more broadly
in the coming months, particularly with the Duchenne community. We
are grateful to the patients, families, investigators and site
teams, whose support has been critical to the advancement of this
program.”
Results and Safety
Results from Study SRP-9001-103, ENDEAVOR
(commercially representative material):
- In Cohort 1 (n=20, ages 4 to 7),
SRP-9001-treated patients demonstrated a 3.8-point improvement
(unadjusted means) and a 3.2-point improvement (least squared
means) on the NSAA one-year after treatment when compared to a
propensity-score weighted external control (p=0.0001).
- At one year, using unadjusted
means, NSAA total scores in the SRP-9001 treated patients improved
4 points from 22.1 to 26.1 and participants in the external control
improved 0.2 points from 21.9 to 22.1.
- At one year, using least squared
means, NSAA total scores in the SRP-9001 treated patients improved
3.9 points and participants in the external control improved 0.8
points (difference 3.2 points allowing for appropriate
rounding).
- Participants in the study also
recorded statistically significant improvements in timed function
tests one year after treatment compared to external control
- At one year, using unadjusted
means, time to rise in the SRP-9001 treated patients improved 0.9
seconds compared to external control
- At one year, using least squared
means, time to rise in the SRP-9001 treated patients improved 1.2
seconds compared to external control (p <0.0001)
- At one year, using unadjusted
means, SRP-9001 treated patients improved 1.0 seconds on the
ten-meter walk test compared to external control
- At one year, using least squared
means, SRP-9001 treated patients improved 1.0 seconds on the
ten-meter walk test compared to external control (p = 0.0018)
Results from Study SRP-9001-101:
- In long-term results from Study
SRP-9001-101, after four years, SRP-9001-treated participants (n=4,
ages 4-7 at time of treatment) had a positive mean 7.0-point
difference on total NSAA scores compared to baseline. These
patients are now on average over 9 years old, an age where one
would expect to see rapid declines in function.
- When compared to a
propensity-weighted external control, total NSAA scores for the
SRP-9001 treated patients were 9.9 points (unadjusted means) and
9.4 points (least square means) greater (p=0.0125).
Results from Integrated Analysis of Studies 101,
102 and 103 versus propensity weighted external control:
- In an integrated analysis of
one-year functional data from patients who received the target dose
of SRP-9001 in Studies 101, 102 and 103 (n=52), SRP-9001-treated
patients improved 3.1 points (unadjusted means) and 2.3 points
(least squared means) in NSAA total scores from baseline
- When compared to the
propensity-weighted external control group, NSAA change from
baseline one-year after treatment for SRP-9001 treated patients was
2.4 points higher (p=0.001).
The safety and tolerability profile of SRP-9001
is similar to past reports. The most common treatment-related
adverse event was vomiting. Increases in liver enzymes were
transient and responsive to steroids. In Study 9001-103, there was
one new serious adverse event of myocarditis in Cohort 2 (older
ambulatory patients >8 years old). The patient had no signs or
symptoms of systolic dysfunction and received IV
methyl-prednisolone and additional chronic cardiac medications
added post-event. Cardiac MRI at one month showed normal function
and partial resolution of myocarditic changes, and ECHO
at four months showed normal systolic function.
*The NSAA is a 17-item rating scale that is used
to measure functional motor abilities in ambulant individuals with
Duchenne. It is used to monitor the progression of the disease and
treatment effects and its reliability and reproducibility make it
suitable as an endpoint in clinical trials for Duchenne.
**The external control used contemporary
datasets taken from three separate studies in Duchenne, two
randomized controlled clinical trials and one natural history
study, creating a prospectively defined consolidated comparison
group of Duchenne patients, matched for variables, including age,
steroid usage, baseline NSAA and timed function tests with the
participants across the SRP-9001 clinical development program. The
prospectively defined propensity score analysis allows for a robust
and rigorous balancing of multiple variables.
About the SRP-9001 Clinical Development
ProgramThe SRP-9001 clinical development program currently
consists of four studies:
- EMBARK, Study
SRP-9001-301: a global, randomized, double-blind,
placebo-controlled clinical trial of commercially representative
SRP-9001 material in 120 participants with Duchenne muscular
dystrophy between the ages of 4 to 7. The primary endpoint will
assess the change in NSAA total score from baseline to week 52
compared to placebo.Key features of EMBARK include stratification
of participants by age and baseline NSAA, with a minimum of 50
percent of patients ages 4 to 5 enrolled. Inclusion criteria
include a stable daily dose of oral corticosteroids for at least 12
weeks before screening and rAAVrh74 antibody titers of less than
1:400. Participants with mutations between or including exons 1-17
or mutations fully contained within exon 45 (inclusive) are not
eligible.
- ENDEAVOR, Study
SRP-9001-103 (Study 103): an open-label
clinical trial of SRP-9001 that has enrolled 38 participants with
Duchenne muscular dystrophy, with 20 participants ages 4 to 7 and
expanded cohorts that include older ambulant and non-ambulant
individuals, and a younger cohort. Study 103 uses commercially
representative SRP-9001 material and the primary endpoint is the
change from baseline in the quantity of micro-dystrophin protein
expression measured by western blot at 12 weeks. Secondary outcome
measures include change from baseline in micro-dystrophin
expression fiber intensity as measured by immunofluorescence (IF)
and micro-dystrophin expression measured by IF percent dystrophin
positive fibers at 12 weeks. Exploratory endpoints include the
change in vector genome copies per nucleus, NSAA and certain timed
functional tests. Including the initial 12-week period, patients
will be followed for a total of five years.
- Study SRP-9001-102 (Study
102): a double-blind, 1:1 randomized, placebo-controlled
clinical trial of SRP-9001 in 41 participants with Duchenne
muscular dystrophy between the ages of 4 to 7. Study 102 uses
clinical process SRP-9001 material and has two primary endpoints:
micro-dystrophin expression at 12 weeks and change in NSAA total
score at 48 weeks compared to placebo. Secondary endpoints include
certain timed functional tests; micro-dystrophin expression
measured by immunofluorescence fiber intensity; and
micro-dystrophin expression measured by immuno-fluorescence percent
dystrophin positive fibers. In Part 1, results from the treatment
and placebo groups are compared through 48 weeks following
treatment. In Part 2, the study remains blinded while all
participants in the placebo group cross over to active treatment
and all participants are followed for another 48 weeks while safety
and efficacy continue to be evaluated and for five years total
after infusion.
- SRP-9001-101 (Study
101): a single-center, open-label clinical trial of
SRP-9001 to evaluate the safety, tolerability and proof of concept
of a single dose of clinical process SRP-9001 material. The trial
enrolled 4 ambulatory participants with Duchenne muscular dystrophy
between the ages of 4 to 7. The primary endpoint was safety, and
secondary endpoint included the change in micro-dystrophin
expression pre- and post-treatment, decreases in creatine kinase,
NSAA total score and timed function test. Participants are being
followed for five years after treatment, while safety and efficacy
continue to be evaluated.
About SRP-9001 (delandistrogene
moxeparvovec) SRP-9001 (delandistrogene moxeparvovec) is
an investigational gene transfer therapy intended to deliver
SRP-9001 to muscle tissue for the targeted production of essential
components of dystrophin. Sarepta is responsible for global
development and manufacturing for SRP-9001 and plans to
commercialize SRP-9001 in the United States upon receiving FDA
approval. In December 2019, Roche partnered with Sarepta to combine
Roche’s global reach, commercial presence and regulatory expertise
with Sarepta’s gene therapy candidate for Duchenne to accelerate
access to SRP-9001 for patients outside the United States.
About Duchenne Muscular
Dystrophy Duchenne muscular dystrophy (DMD) is a rare,
fatal neuromuscular genetic disease that occurs in approximately
one in every 3,500-5,000 newborn males worldwide. DMD is caused by
a change or mutation in the gene that encodes instructions for
dystrophin. Symptoms of DMD usually appear in infants and toddlers.
Affected children may experience developmental delays such as
difficulty in walking, climbing stairs or standing from a sitting
position. As the disease progresses, muscle weakness in the lower
limbs spreads to the arms and other areas. Most patients require
full-time use of a wheelchair in their early teens, and then
progressively lose the ability to independently perform activities
of daily living such as using the restroom, bathing and feeding.
Eventually, increasing difficulty in breathing due to respiratory
muscle dysfunction requires ventilation support, and cardiac
dysfunction can lead to heart failure. The condition is universally
fatal, and patients usually succumb to the disease in their
twenties.
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.
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.
Forward-Looking StatementsThis 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 statements relating to the potentially transformative
benefits of SRP-9001; our ongoing Phase 3 Study SRP-9001-301
EMBARK; the potential market opportunities with respect to
Duchenne; and our plan to share data more broadly in the coming
months, particularly with the Duchenne community.
These forward-looking statements involve risks
and uncertainties, many of which are beyond our control. Known risk
factors include, among others: success in pre-clinical trials and
early 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 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
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; 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, 2021, 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,
except as required by law.
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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