February 17, 2023

Hello U.S. LGMD advocacy, patient, and caregiver community,

Sarepta is pleased to introduce two clinical studies in our Limb-girdle muscular dystrophy (LGMD) development efforts: The VOYAGENE study for LGMD2E/R4 and the NAVIGENE study for LGMD2B/R2.

  • VOYAGENE (SRP-9003-102) for LGMD2E/R4:
    Screening is open for the VOYAGENE study, a multicenter, open-label, single-dose, systemic gene transfer study in the U.S. to evaluate the safety, tolerability, and efficacy of SRP-9003 in individuals living with LGMD2E/R4 (β -sarcoglycanopathy). VOYAGENE will enroll approximately five individuals and will include individuals who are ambulatory and non-ambulatory.  Additional detail may be found below in the SRP-9003 section of this letter.
  • NAVIGENE (SRP-6004-102) for LGMD2B/R2:
    In the first half of 2023, Sarepta plans to initiate a proof-of-concept Phase I study called NAVIGENE (SRP-6004-102) to evaluate systemic delivery in individuals living with LGMD 2B/R2 (dysferlinopathy). We anticipate enrolling approximately 2 ambulatory individuals.  Additional detail may be found below in the SRP-6004 section of this letter.


What is SRP-9003?
SRP-9003 is an investigational gene therapy being developed to address LGMD2E/R4 (β -sarcoglycanopathy). It is designed to help muscle cells make the missing β-sarcoglycan (β-SG) protein and, in turn, it aims to slow or stabilize the disease. SRP-9003 is investigational, meaning that the safety and efficacy of SRP-9003 have not been established.

What is the primary goal of VOYAGENE?
Following results in the initial phase 1 study of SRP-9003-101 in which two different doses were explored, VOYAGENE will allow us to gather additional safety and efficacy data on the selected dose of SRP-9003 in a wider population of patients as we work to finalize plans for a global phase 3 study (SRP-9003-301).  VOYAGENE will allow for the evaluation of SRP-9003 gene therapy in individuals who are older, or more severely affected by LGMD 2E/R4, and the study will include individuals who are ambulatory or non-ambulatory. The primary goal of VOYAGENE is to evaluate the safety of SRP-9003.

What are the entry criteria for VOYAGENE and where is the study taking place?
VOYAGENE will take place in the U.S. Individuals living with LGMD 2E/R4 are eligible to be included in the study based on multiple factors including, but not limited to age, body weight, genetic subtype, functional ability, motor assessment testing, and antibody testing. Further information on the entry criteria for this study may be found at VOYAGENE.

How did you choose the size of the VOYAGENE study?
VOYAGENE is designed to evaluate the safety, tolerability, and efficacy of a selected dose of investigational SRP-9003 gene therapy in a wider range of study participants than has been studied in the past. VOYAGENE is sized to meet the objectives of the study. We will use the learnings from VOYAGENE to inform the development program moving forward.

Has there been a prior study of SRP-9003 for LGMD2E/R4?
Long-term follow up and data collection are ongoing for SRP-9003-101, a phase 1 clinical study of SRP-9003 for people who are ambulatory and living with LGMD2E/R4. The study measured beta-sarcoglycan protein expression via muscle biopsies following a single infusion of SRP-9003.

What is the status of larger-scale studies for LGMD2E/R4?
Work continues toward finalizing plans for a global phase 3 study, SRP-9003-301, in people living with LGMD2E/R4. Different from previous studies, SRP-9003-301 will require a natural history lead-in period prior to gene therapy dosing.  Individuals who have participated in one of two natural history studies -- JOURNEY or GRASP – and have documented, suitable longitudinal follow-up data would not require completion of a separate natural history lead-in as part of their enrollment into Study SRP-9003-301. Individuals with LGMD2E who have not participated in JOURNEY or GRASP but have fulfilled the entry criteria for study SRP-9003-301 will also be considered for study participation.

The company will share an update about the larger scale SRP-9003-301 study as the details are finalized and the study draws nearer.

What is the status of JOURNEY and GRASP?
JOURNEY and GRASP are natural history studies for people living with various LGMD subtypes and both studies continue to enroll participants. Sarepta sponsors JOURNEY, which will be a key contributor in moving our work in LGMD forward. If you wish to learn more about the JOURNEY natural history study and potentially enroll you may visit the website here. Additional information about GRASP may be found here. Learnings from JOURNEY will enable deeper understanding of LGMD types 2E/R4, 2D/R3, and 2C/R5, and inform how Sarepta approaches the design of future clinical studies across our LGMD pipeline.


What is SRP-6004?
SRP-6004 is Sarepta’s investigational gene therapy being developed for the treatment of LGMD2B/R2. Sarepta’s investigational LGMD gene therapy, SRP-6004, is designed to express the full-length protein dysferlin that is missing in individuals with LGMD2B/R2. Safety and efficacy of SRP-6004 have not been established.

What is the primary goal of NAVIGENE?
NAVIGENE (SRP-6004-102) is an open-label, systemic gene transfer study to evaluate the safety, tolerability, and efficacy of SRP-6004 administered by systemic infusion in ambulatory individuals living with LGMD2B/R2 (dysferlin related). The primary objective of NAVIGENE is to evaluate safety.

What are the entry criteria for NAVIGENE and where will the study be taking place?
Inclusion criteria for this U.S. study will include, but will not be limited to age, body weight, genetic subtype, functional ability, motor assessment testing, and antibody testing. Updates on details of the study, which is expected to initiate in the first half of 2023, will be added to https://genesislgmd.com/ when it is available.

How did you choose the size of the NAVIGENE study?
NAVIGENE is designed as a small, proof-of-concept study to evaluate the systemic (IV) delivery of SRP-6004 for the first time in humans. As such, NAVIGENE is sized to meet the objectives of the study, with safety being a primary objective. We will use the learnings from this study to inform the development program moving forward, which would include studies with a larger number of participants.

Has there been a prior study of SRP-6004 in LGMD2B/R2?
In a prior study, SRP-6004 was administered via IM (intramuscular) injection; the investigational gene therapy was administered directly into the muscle. In the NAVIGENE study, SRP-6004 will be administered via systemic, intravenous (IV) dosing, which goes directly to the bloodstream. The goal of IV administration is to enable the therapy to reach a greater number of muscles in the body. NAVIGENE is a proof-of-concept study that will inform LGMD2B/R2 research and development.

What are the challenges of administering the dysferlin transgene?
There is a unique complexity with the full-length dysferlin transgene: it is too large to fit inside the selected vector. The vector serves as a vehicle responsible for carrying the gene of interest directly into the cell. Sarepta’s proposed solution is to use a dual-vector approach in which the full transgene is divided in two and administered using two vectors in order to produce the full-length dysferlin protein in muscle cells.


Where may I learn more?

  • For updates and information about Sarepta’s LGMD clinical studies you may visit https://genesislgmd.com/
  • You may also visit www.clinicaltrials.gov for broader awareness of clinical studies
  • Please contact your doctor to discuss your interest in clinical study participation.
  • For additional questions or to connect with Sarepta, please contact our Patient Affairs team by emailing [email protected]
  • There are several genetic testing programs available for individuals with LGMD. Information may be found at Limbgirdle.com

Are there updates about other Sarepta LGMD pipeline programs?
Sarepta is advancing preclinical, toxicology and manufacturing process development for four additional subtypes in our pipeline: SRP-9004 for LGMD2D/R3; SRP-9005 for LGMD2C/R5; SRP-9006 for LGMD2L/R12; SRP-9010 for LGMD2A/R1. We look forward to sharing updates in the future as these programs continue to progress.

Sarepta’s investigational gene therapies for LGMD have a number of commonalities in their biological design and in how they are constructed. We are applying knowledge gained across research programs to advance development across the LGMD pipeline.

We are grateful to study participants, families, caregivers, and the study teams at the clinical trial sites. We look forward to providing additional updates on our LGMD programs in the future.

With our kind regards,

The Sarepta Patient Affairs Team
[email protected]