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Sarepta announces top-line results for its investigational gene therapy

Sarepta Therapeutics announces top-line results for part 1 of study 102 evaluating SRP-9001, its investigational gene therapy for the treatment of Duchenne muscular dystrophy (DMD)


Jan. 7, 2021, >Original press release<

Sarepta Therapeutics, Inc. announced top-line results from Part 1 of Study SRP-9001 (Study 102), an ongoing, randomized, double-blind, placebo-controlled clinical trial to evaluate the safety, efficacy and tolerability of a single dose of SRP-9001 (rAAVrh74.MHCK7.micro-dystrophin) in 41 patients with Duchenne muscular dystrophy. SRP-9001 is an investigational gene transfer therapy intended to deliver its micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein.


  • The study met the primary biological endpoint of micro-dystrophin protein expression at 12 weeks post-treatment, measured by western blot, in SRP-9001-treated participants versus placebo.
  • SRP-9001-treated participants showed an increase in NSAA total score compared to placebo at 48 weeks; however, the study did not achieve statistical significance on the primary functional endpoint of improvement in NSAA total score compared to placebo at 48 weeks post-treatment  
  • In the pre-specified analysis by age-group, by which the randomization was stratified, participants aged 4-5 years at the time of treatment with SRP-9001 demonstrated a statistically significant improvement in NSAA total score age-matched placebo cohort, achieving a 4.3-point improvement on NSAA at 48 weeks post-treatment from baseline.
  • No new safety signals were identified for SRP-9001, reinforcing the favourable safety profile observed to date.

Study 102 is ongoing and remains blinded to participants, investigators, site staff and sponsor staff with direct site interaction. All 41 participants have completed their Part 1, 48-week assessment and have entered the Part 2 crossover phase. Participants continue to be monitored for safety and will undergo another biopsy at week 12 in Part 2 to assess the expression and biological markers, in addition to longer-term assessments of functional outcomes.


Doug Ingram, president and chief executive officer, Sarepta – “Study 102 reinforces our confidence in the potentially transformative benefits of SRP-9001, including among other things, the fact that in the Study’s pre-specified analysis, the participants in the 4-5 age group robustly achieved a statistically significant and clinically meaningful improvement in NSAA over placebo, as predicted by our prior Study 101. For the entire population, while we saw separation at every time point between the active and placebo cohorts, Study 102 did not achieve statistical significance on the primary functional endpoint. In this regard, we are very disappointed that the randomization process resulted in a significant imbalance in baseline NSAA scores between the active and placebo cohorts of the participants ages 6-7, making the 6-7 age groups non-comparable and likely substantially contributing to the inability to achieve statistical significance. Study 102 remains blinded and we will analyze the functional results for all patients, including cross-over participants, once they have achieved the 48-week timepoint in Part 2. We have already enrolled and dosed 11 participants in Study 103, using our commercial process material, and we will have biomarker and safety results from that cohort in the second quarter. And very importantly, Study 102 has provided us with a wealth of information and insight which we will use to refine and complete the protocol for our upcoming trial using commercial process material. We intend to continue to move forward with diligence and urgency to generate the evidence necessary to bring SRP-9001 to waiting Duchenne patients around the world.”


*The NSAA is a 17-item rating scale used to measure functional motor abilities in ambulant children with Duchenne. It is used to monitor the disease’s progression and treatment effects, which makes it suitable as an endpoint in clinical trials for Duchenne.

About Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a rare, fatal neuromuscular genetic disease in approximately one in every 3,500-5,000 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, neck 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 daily living activities such as using the restroom, bathing and feeding. Eventually, increasing breathing difficulty 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 SRP-9001 (rAAVrh74.MHCK7.micro-dystrophin)

SRP-9001 is an investigational gene transfer therapy intended to deliver the micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein. 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, the Company announced a licensing agreement granting Roche the exclusive right to launch and commercialize SRP-9001 outside the United States. Sarepta has exclusive rights to the micro-dystrophin gene therapy program initially developed at the Abigail Wexner Research Institute at Nationwide Children’s Hospital.

About Sarepta

Sarepta Therapeutics, Inc., a biopharmaceutical company, is working to unlock the potential of RNA-based and gene therapy technologies to treat serious and life-threatening diseases like Duchenne muscular dystrophy (DMD). Sarepta’s primary focus is to advance new treatments for DMD rapidly.

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Pfizer doses the first participant with Its gene therapy

Pfizer doses the first participant in phase 3 study for Duchenne muscular dystrophy (DMD) investigational gene therapy.

Pfizer Inc. announced that the first participant has been dosed in the Phase 3 CIFFREO study, which will evaluate the efficacy and safety of investigational gene therapy candidate PF-06939926 in boys with Duchenne muscular dystrophy (DMD). The CIFFREO trial is expected to enroll 99 ambulatory male patients, ages 4 through 7, across 55 clinical trial sites in 15 countries. The first patient was dosed at a site in Barcelona, Spain, on December 29, 2020.

CIFFREO is a Phase 3 global, multicenter, randomized, double-blind, placebo-controlled study. The study’s primary endpoint is the change from baseline in the North Star Ambulatory Assessment (NSAA) at one year. The NSAA is a 17-item test that measures gross motor function in boys with DMD. Regardless of the cohort, eligible participants are scheduled to receive the investigational gene therapy, either at the start of the study or after one year following treatment with placebo. Participants will be followed in the CIFFREO study for five years after treatment with the investigational gene therapy. Trial participants will receive commercially representative drug products manufactured at Pfizer’s state-of-the-art gene therapy manufacturing facility in Sanford, North Carolina.


Brenda Cooperstone, MD, Chief Development Officer, Rare Disease, Pfizer Global Product Development  – “The initiation of our pivotal trial, which is the first Phase 3 DMD gene therapy program to begin enrolling eligible participants, is an important milestone for the community because there are currently no approved disease-modifying treatment options available for all genetic forms of DMD. We believe our gene therapy candidate, if successful in Phase 3 and approved, has the potential to significantly improve the trajectory of DMD disease progression, and we are working with worldwide regulatory authorities to initiate this program as quickly as possible in other countries.”


PF-06939926 received Fast Track designation from the U.S. Food and Drug Administration in October 2020 (read article), as well as Orphan Drug and Rare Pediatric Disease designations in the United States in May 2017.


Silvia Avila, President, Duchenne Parent Project Spain  – “DMD is a progressive disorder, and patients and parents are waiting desperately for treatment options. The initiation of this study is an important step forward for this community, and it fuels us with hope that one day there may be treatment options for boys impacted with this devastating disease.”


DMD is an X-linked disease caused by mutations in the gene encoding dystrophin, which is needed for muscle membrane stability. Due to the lack of dystrophin, boys present with muscle degeneration that progressively worsens with age to the extent that they require wheelchair assistance when they are in their early teens, and unfortunately, usually succumb to their disease by the time they are in their late twenties. It is estimated that there are ~140,000 boys affected by DMD worldwide.



CIFFREO is a Phase 3 global, multi-center, randomized, double-blind, placebo-controlled study to assess the safety and efficacy of PF-06939926 investigational gene therapy in 99 ambulatory male participants, ages 4 through 7 years, with a genetic diagnosis of DMD who are on a stable daily regimen of glucocorticoids. The participants are negative for neutralizing antibodies against AAV9, as measured by the test done for the study as part of screening.

Eligible participants will be randomized into Cohort 1 or Cohort 2. Treatment will consist of two single intravenous infusions, one of PF-06939926 and one of placebo; approximately two thirds will be in Cohort 1 and receive PF-06939926 gene therapy at the start of the study and placebo after one year, and approximately one third will be in Cohort 2 and receive placebo at the start of the study and receive gene therapy after one year if they remain eligible. All participants will be followed in an open-label extension study for 5 years after treatment with the gene therapy. The study’s primary endpoint is a change from baseline at one year in the North Star Ambulatory Assessment (NSAA) total score. For more information, visit ciffreoduchennetrial.com.


About PF-06939926

PF-06939926 is an investigational recombinant adeno-associated virus serotype 9 (rAAV9) capsid carrying a shortened version of the human dystrophin gene (mini-dystrophin) under the control of a human muscle specific promotor. The rAAV9 capsid was chosen as the delivery vector because of its potential to target muscle tissue.


About Pfizer Rare Disease

Rare disease includes some of the most serious of all illnesses and impacts millions of patients worldwide, representing an opportunity to apply their knowledge and expertise to help make a significant impact on addressing unmet medical needs. The Pfizer focus on rare diseases builds on more than two decades of experience, a dedicated research unit focusing on rare disease, and a global portfolio of multiple medicines within several disease areas of focus, including rare hematologic, neurologic, cardiac and inherited metabolic disorders.

Pfizer Rare Disease combines pioneering science and a deep understanding of how diseases work with insights from innovative strategic collaborations with academic researchers, patients, and other companies to deliver transformative treatments and solutions. Pfizer innovates every day, leveraging its global footprint to accelerate the development and delivery of groundbreaking medicines and the hope of cures.

Click here to learn more about their Rare Disease portfolio and how Pfizer empowers patients, engage communities in their clinical development programs, and support programs that heighten disease awareness.