Sarepta Therapeutics Announces Results from Part 2 of the EMBARK Study Demonstrating Sustained Benefits and Disease Stabilization in Ambulatory Individuals with Duchenne Muscular Dystrophy Following Treatment with ELEVIDYS
– Treatment with ELEVIDYS corresponded with increases on the North Star Ambulatory Assessment (NSAA) at one year in crossover patients, while the study remained blinded
– MRI results at two years in patients treated in Part 1 show minimal muscle pathology progression, aligning closely with observed functional benefits
– Crossover-treated patients show statistically significant benefits of ELEVIDYS treatment on NSAA, Time to Rise (TTR), and 10-meter walk/run (10MWR), when compared to a pre-specified, well-matched external control (EC)
– Part 1-treated patients show sustained expression at week 64, and functional improvements on NSAA, TTR and 10MWR were sustained two years after treatment and show a widening divergence compared to EC
– Safety remained consistent with the profile of ELEVIDYS already established across a broad Duchenne population
– Investor webcast to be held today at 8:30 a.m. ET
CAMBRIDGE, MA, USA I January 28, 2025 I Sarepta Therapeutics, Inc. (NASDAQ: SRPT), the leader in precision genetic medicine for rare diseases, today announced positive topline results from Part 2 of EMBARK (Study SRP-9001-301), a global, randomized, double-blind, placebo-controlled, Phase 3 clinical study of ELEVIDYS (delandistrogene moxeparvovec-rokl), the only approved gene therapy in patients with Duchenne muscular dystrophy.
Crossover-treated patients, those who received a placebo in Part 1 and crossed over at 52 weeks and were treated with ELEVIDYS in Part 2, improved 2.34 points from baseline compared to matched external controls on the North Star Ambulatory Assessment (NSAA) 52 weeks after treatment (P<0.0001), during which time the study remained blinded.
Despite being one year older (average age 7.18 years) than those treated in Part 1 (average age 5.98 years), crossover-treated patients showed clinically meaningful and statistically significant functional benefit for NSAA, Time to Rise (TTR), and 10-meter walk/run (10MWR) function tests compared with a pre-specified, propensity-weighted external control group* (EC).
Crossover-Treated Patients (n=59) vs. EC
Functional Outcomes
LSM
P-Value
NSAA
+2.34 points
P<0.0001
TTR
-2.70 seconds (improvement)
P<0.0001
10MWR
-1.07 seconds (improvement)
P=0.0001
Two-Year Results
In patients treated in Part 1, biopsies taken 64 weeks after dosing showed consistent and sustained expression of ELEVIDYS micro-dystrophin compared to week 12 biopsies, as measured by western blot, and provide biological support for observed functional outcomes.
At two years, patients treated in Part 1 of EMBARK showed clinically meaningful and statistically significant functional benefit in NSAA, TTR and 10MWR compared with EC. Furthermore, the least square means (LSM) differences seen between the patients treated in Part 1 and the EC group increase from year one to year two for all three functional outcomes. This indicates that the trajectory of disease in patients treated with ELEVIDYS is continuing to diverge from the natural history of DMD.
Part 1, Year 2 (n=63) ELEVIDYS-Treated vs. EC
Functional Outcomes
LSM
P-Value
NSAA
+2.88 points
P=0.0001
TTR
-2.06 seconds (improvement)
P=0.0033
10MWR
-1.36 seconds (improvement)
P=0.0028
Skeletal muscle MRI conducted on patients treated in Part 1 found minimal progression in underlying muscle pathology and remain highly consistent with the functional benefits shown.
“We’re very encouraged to see the results from Part 2 of EMBARK as they further elucidate the impact ELEVIDYS has on disease progression in a blinded, controlled study. Skeletal muscle MRI demonstrates the importance of preserving muscle, and the functional outcome results show disease stabilization sustained through two years after treatment,” said Louise Rodino-Klapac, Ph.D., executive vice president, Head of R&D, Chief Scientific Officer. “Over time, we continue to observe a statistically significant difference favoring ELEVIDYS compared to a well-matched external control on NSAA and timed tests. The consistency and totality of evidence supporting a long-term and clinically meaningful treatment benefit with ELEVIDYS continues to grow. We look forward to sharing more details with the clinical community in upcoming scientific forums.”
No new safety signals were observed, reinforcing the consistent and manageable safety profile of ELEVIDYS to date. Detailed results from Part 2 of the EMBARK study will be shared at future medical meetings.
“As a neuromuscular medicine specialist who has seen patients with Duchenne muscular dystrophy for over three decades, I’ve witnessed firsthand the positive impact of gene therapy on the trajectory of Duchenne,” 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. “These longer-term results are even more striking when compared to external control given the progressive nature of the disease, and we’d expect to see this divergence grow over time. The efficacy of ELEVIDYS gives me great hope as we continue to follow these patients and see others treated in the clinical setting.”
As part of a collaboration agreement signed in 2019, Sarepta is working with Roche to transform the future for the Duchenne community, enabling those living with the disease to maintain and protect their muscle function. 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.
ELEVIDYS is approved for people living with Duchenne aged four years old and over regardless of their ambulatory status in the U.S., United Arab Emirates (UAE), Qatar, Kuwait, Bahrain and Oman. ELEVIDYS is also approved for the treatment of ambulatory patients aged four through seven years in Brazil and Israel.
*The pre-specified external control used data from five separate studies in Duchenne, comprising DMD controls from two randomized trials and three natural history cohorts who met predefined matching criteria. Comparison of treated and control patients was based on a pre-specified, propensity score weighting approach using age, steroid usage, baseline NSAA and timed function tests in order to balance key prognostic factors between the groups.
Sarepta Investor Call Details
At 8:30 a.m. ET on Jan. 27, 2025, 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.
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 remained blinded through Part 1 and Part 2.
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. One-year results from the Part 1 placebo-controlled period of the EMBARK study were published in Nature Medicine in October 2024.
About ELEVIDYS (delandistrogene moxeparvovec-rokl)
ELEVIDYS (delandistrogene moxeparvovec-rokl) is a single-dose, adeno-associated virus (AAV)-based gene transfer therapy for intravenous infusion designed to address the underlying genetic cause of Duchenne muscular dystrophy – mutations or changes in the DMD gene that result in the lack of dystrophin protein – through the delivery of a transgene that codes for the targeted production of ELEVIDYS micro-dystrophin in skeletal muscle.
ELEVIDYS is indicated for the treatment of Duchenne muscular dystrophy (DMD) in individuals at least 4 years of age.
For patients who are ambulatory and have a confirmed mutation in the DMD gene
For patients who are non-ambulatory and have a confirmed mutation in the DMD gene.
The DMD indication in non-ambulatory patients is approved under accelerated approval based on expression of ELEVIDYS micro-dystrophin (noted hereafter as “micro-dystrophin”) in skeletal muscle. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
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 LinkedIn, X, Instagram and Facebook.
– Treatment with ELEVIDYS corresponded with increases on the North Star Ambulatory Assessment (NSAA) at one year in crossover patients, while the study remained blinded
– MRI results at two years in patients treated in Part 1 show minimal muscle pathology progression, aligning closely with observed functional benefits
– Crossover-treated patients show statistically significant benefits of ELEVIDYS treatment on NSAA, Time to Rise (TTR), and 10-meter walk/run (10MWR), when compared to a pre-specified, well-matched external control (EC)
– Part 1-treated patients show sustained expression at week 64, and functional improvements on NSAA, TTR and 10MWR were sustained two years after treatment and show a widening divergence compared to EC
– Safety remained consistent with the profile of ELEVIDYS already established across a broad Duchenne population
– Investor webcast to be held today at 8:30 a.m. ET
CAMBRIDGE, MA, USA I January 28, 2025 I Sarepta Therapeutics, Inc. (NASDAQ: SRPT), the leader in precision genetic medicine for rare diseases, today announced positive topline results from Part 2 of EMBARK (Study SRP-9001-301), a global, randomized, double-blind, placebo-controlled, Phase 3 clinical study of ELEVIDYS (delandistrogene moxeparvovec-rokl), the only approved gene therapy in patients with Duchenne muscular dystrophy.
Crossover-treated patients, those who received a placebo in Part 1 and crossed over at 52 weeks and were treated with ELEVIDYS in Part 2, improved 2.34 points from baseline compared to matched external controls on the North Star Ambulatory Assessment (NSAA) 52 weeks after treatment (P<0.0001), during which time the study remained blinded.
Despite being one year older (average age 7.18 years) than those treated in Part 1 (average age 5.98 years), crossover-treated patients showed clinically meaningful and statistically significant functional benefit for NSAA, Time to Rise (TTR), and 10-meter walk/run (10MWR) function tests compared with a pre-specified, propensity-weighted external control group* (EC).
Crossover-Treated Patients (n=59) vs. EC
Functional Outcomes
LSM
P-Value
NSAA
+2.34 points
P<0.0001
TTR
-2.70 seconds (improvement)
P<0.0001
10MWR
-1.07 seconds (improvement)
P=0.0001
Two-Year Results
In patients treated in Part 1, biopsies taken 64 weeks after dosing showed consistent and sustained expression of ELEVIDYS micro-dystrophin compared to week 12 biopsies, as measured by western blot, and provide biological support for observed functional outcomes.
At two years, patients treated in Part 1 of EMBARK showed clinically meaningful and statistically significant functional benefit in NSAA, TTR and 10MWR compared with EC. Furthermore, the least square means (LSM) differences seen between the patients treated in Part 1 and the EC group increase from year one to year two for all three functional outcomes. This indicates that the trajectory of disease in patients treated with ELEVIDYS is continuing to diverge from the natural history of DMD.
Part 1, Year 2 (n=63) ELEVIDYS-Treated vs. EC
Functional Outcomes
LSM
P-Value
NSAA
+2.88 points
P=0.0001
TTR
-2.06 seconds (improvement)
P=0.0033
10MWR
-1.36 seconds (improvement)
P=0.0028
Skeletal muscle MRI conducted on patients treated in Part 1 found minimal progression in underlying muscle pathology and remain highly consistent with the functional benefits shown.
“We’re very encouraged to see the results from Part 2 of EMBARK as they further elucidate the impact ELEVIDYS has on disease progression in a blinded, controlled study. Skeletal muscle MRI demonstrates the importance of preserving muscle, and the functional outcome results show disease stabilization sustained through two years after treatment,” said Louise Rodino-Klapac, Ph.D., executive vice president, Head of R&D, Chief Scientific Officer. “Over time, we continue to observe a statistically significant difference favoring ELEVIDYS compared to a well-matched external control on NSAA and timed tests. The consistency and totality of evidence supporting a long-term and clinically meaningful treatment benefit with ELEVIDYS continues to grow. We look forward to sharing more details with the clinical community in upcoming scientific forums.”
No new safety signals were observed, reinforcing the consistent and manageable safety profile of ELEVIDYS to date. Detailed results from Part 2 of the EMBARK study will be shared at future medical meetings.
“As a neuromuscular medicine specialist who has seen patients with Duchenne muscular dystrophy for over three decades, I’ve witnessed firsthand the positive impact of gene therapy on the trajectory of Duchenne,” 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. “These longer-term results are even more striking when compared to external control given the progressive nature of the disease, and we’d expect to see this divergence grow over time. The efficacy of ELEVIDYS gives me great hope as we continue to follow these patients and see others treated in the clinical setting.”
As part of a collaboration agreement signed in 2019, Sarepta is working with Roche to transform the future for the Duchenne community, enabling those living with the disease to maintain and protect their muscle function. 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.
ELEVIDYS is approved for people living with Duchenne aged four years old and over regardless of their ambulatory status in the U.S., United Arab Emirates (UAE), Qatar, Kuwait, Bahrain and Oman. ELEVIDYS is also approved for the treatment of ambulatory patients aged four through seven years in Brazil and Israel.
*The pre-specified external control used data from five separate studies in Duchenne, comprising DMD controls from two randomized trials and three natural history cohorts who met predefined matching criteria. Comparison of treated and control patients was based on a pre-specified, propensity score weighting approach using age, steroid usage, baseline NSAA and timed function tests in order to balance key prognostic factors between the groups.
Sarepta Investor Call Details
At 8:30 a.m. ET on Jan. 27, 2025, 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.
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 remained blinded through Part 1 and Part 2.
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. One-year results from the Part 1 placebo-controlled period of the EMBARK study were published in Nature Medicine in October 2024.
About ELEVIDYS (delandistrogene moxeparvovec-rokl)
ELEVIDYS (delandistrogene moxeparvovec-rokl) is a single-dose, adeno-associated virus (AAV)-based gene transfer therapy for intravenous infusion designed to address the underlying genetic cause of Duchenne muscular dystrophy – mutations or changes in the DMD gene that result in the lack of dystrophin protein – through the delivery of a transgene that codes for the targeted production of ELEVIDYS micro-dystrophin in skeletal muscle.
ELEVIDYS is indicated for the treatment of Duchenne muscular dystrophy (DMD) in individuals at least 4 years of age.
For patients who are ambulatory and have a confirmed mutation in the DMD gene
For patients who are non-ambulatory and have a confirmed mutation in the DMD gene.
The DMD indication in non-ambulatory patients is approved under accelerated approval based on expression of ELEVIDYS micro-dystrophin (noted hereafter as “micro-dystrophin”) in skeletal muscle. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
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 LinkedIn, X, Instagram and Facebook.
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