Understanding Gene Therapy Trials & Results Data

Some of the most common questions PPMD receives from families are about clinical trials, and specifically about gene therapy clinical trials. Gene therapy is an area of potential treatment that has shown great promise. However, the last few years have also shown us that there remain many challenges to safely and effectively deliver these potential therapies to all patients.

The resources below were developed as tools to enable families to understand what data is available on the gene therapies so far, as well as the currently enrolling clinical trials. It is important to note that this is a rapidly changing area of research. These resources will be updated, but it is possible that very recent changes or data will not be included.

Please note: There are numerous gene therapy strategies in development for Duchenne. The tables below contain information pertaining only to gene replacement strategies (or, ‘gene addition strategies‘, as they involve adding a new gene to affected cells) with a micro-dystrophin transgene. This strategy is the furthest along in development and testing and is likely to be an option for a large percentage of people with Duchenne. For more information about additional potential gene therapy strategies that are being tested, including gene therapy based exon skipping, visit PPMD’s Drug Development Pipeline.

Current Gene Therapies & Results Data

The table below describes the current gene therapies and gives information so that families can see what they have in common and how they are different. This table also includes very short summaries of results data that have been released thus far, as well as information about side effects.

SareptaPfizerSolid Biosciences
*refers to SGT-003
Current Phase of clinical trialsFDA-approved; ongoing Phase 2 and 3 Clinical trials2 and 31/2*1/2
previously known as SRP-9001
(delandistrogene moxeparvovec-rokl)

Recombinant adeno-associated virus carrying a micro-dystrophin gene
PF-06939926 (fordadistrogene movaparvovec)
Recombinant adeno-associated virus carrying a human mini-dystrophin gene
Recombinant adeno-associated virus containing a next-generation micro-dystrophin gene*
nNOS restorationNoNoYes*No
PromoterMHCK7Hybrid muscle specific promoterCK8*Spc5-12, muscle specific promoter

*Doses in bold are the dose that the company considers effective and is primarily planning to use.
2E14 vg/kgLow dose: 1E14 vg/kg
High dose: 2E14 vg/kg
Route of delivery and frequencyOne time intravenous (IV) infusionOne time IV infusionOne time IV infusion*One time IV infusion
Age range studied (as of December 2023)>2 years2-16 years4-7 years for SGT-003, 4-17 years for SGT-0014-11 years
Total number of boys known to be dosed thus far> 150> 75None dosed yet for SGT-003; 9 were dosed with SGT-0013
Genetic variant limitations in past studiesVariants were required to be within exons 18-58 for the first 4 boys, then all mutations were allowed. EMBARK excluded variants in exons 1-17 and exon 45.None specified in past studies.
Current excluding variants in exons 9-13 and deletions of exons 29-30.
Currently excluding deletions in exons 1-11 and exons 42-45, inclusive*Limiting to variants in exons 18-79.
Data 2020PubMed.gov: 1 year data on the first 4 boys dosed. The data showed no serious adverse events. At one year after dosing, the boys all had functional improvement of NSAA scores and reduced CK compared to prior to treatment. Muscle biopsy showed a mean of 74% of dystrophin on Western blot and 81% of fibers expressing dystrophin. ASGCT 2020: 1 year data on 9 boys ages 6-12, high dose and low dose cohorts. In the 6 boys who had biopsy data at 12 months, mean dystrophin expression (measured by immuno-affinity mass spectrometry) was 24% in the low dose and 52% in the high dose. Mean %positive fibers were 21% in low and 51% in the high dose.
NSAA showed an average improvement of 3.5 points in the 6 boys at 12 months. MRI showed a reduction in fat fraction in the high dose group at 12 months.
Data 2021January 2021 Study 102: Statistically significant increased dystrophin expression (mean of 28% at 12 weeks). Increase in total NSAA score at 48 weeks but not statistically significant. Boys in 4-5 age range did have a statistically significant improvement in NSAA versus the boys on placebo. In the 6-7 boys, the boys on placebo overall had higher baseline NSAA, which may have affected the data analysis.

Jan 2021 Study 101: Three of the initial 4 patients had fat fraction assessment done by MRI through ImagingDMD, independent of the Sarepta study. Minimal fat infiltration was seen compared to boys in natural history studies.

May 2021 on Endeavor: First 11 boys dosed had mean microdystrophin levels of 55% at week 12, with 71% dystrophin positive fibers.

October 2021: Study 101 found that participants (n=4, ages 4 to 7 years) improved 8.6 points on the NSAA compared to a matched natural history cohort three years after treatment. Study 102 found that treated boys (n=12, ages 6 to 7) had a positive 2.9-point difference on NSAA compared to a matched natural history cohort one year after treatment. Study 103 (ENDEAVOR) Cohort 1 (n=11, ages 4-7) found participants improved 3.0 points on NSAA six months after treatment.
MDA March 2021: 19 boys 6-12, high and lose dose cohorts. From 6 boys, NSAA scores were generally improved or stable which was improved compared to an external control group. Starting to enroll non-ambulatory boys.SGT-001 Data (no longer in clinical trial)

MDA March 2021: Muscle biopsies from Cohort B at 90 days showed mean dystrophin of 10%, with %positive fibers 20-70%.

March 2021: Stable NSAA, Mean increase in distance in the 6-Minute walk test, increase in %FVC.

May 2021: 3 boys in Cohort B had biopsies at 12-24 months that showed continued expression (levels of the microdystrophin were below the limit of the test, 70%, and 20%, staying stable or increasing). % positive fibers were at 10-30%, 85%, 50-60%, generally staying the same as the 12 week biopsies.

September 2021: 3 patients at 1.5 years, stability in NSAA, 6MWT, FVC.
Data 2022January 2022: Study 102 participants (n=20, ages 5 to 8) who were initially on placebo and then received gene therapy improved mean NSAA scores by 1.3 points from baseline

July 2022: Study 101 (n=4) patients showed an average of 7 point increase on NSAA over their baseline prior to treatment at 4 years post treatment. Average age of these boys is > 9 years, so their NSAA scores would be expected to be declining.
In Study 103 (n=20), participants improved an average of 4 points from their scores before therapy.
When the 53 patients in 101, 102, and 103 who were dosed the higher dose were combined, at one year after dosing the group had an average NSAA score improvement of 3 points.
MDA March 2022: 19 boys received gene therapy (3 low-dose; 16 high-dose). At one year after dose, NSAA score increased by 1 point, in comparison to an external control cohort (placebo trial participants of similar age, weight, baseline function, and stable steroid use) who had a 4-point decline.

In 14 participants receiving high-dose gene therapy, mean minidystrophin expression at 12 months was 40%, with %positive fibers of 62%.
SGT-001 Data (no longer in clinical trial)
March 2022: Data from the first three high-dose participants suggest improved muscle and lung function at 2 years after the dose. Muscle biopsy data from 3 most recently diagnosed patients show microdystrophin levels similar to what was seen in cohort B at 90 days after dose.
Recruitment opened January 2023
Data 2023November 2023: Topline results of the EMBARK study at 52 weeks did not meet the primary endpoint (NSAA) but data showed substantial evidence of safety and effectiveness based on secondary endpoints, time function tests.October 2023: At 12 weeks after dosing, muscle biopsy on the first two boys treated showed "robust" microdystrophin expression with microdystrophin present in the muscle cell membrane.
Adverse events notedVomiting, decreased appetite, and nausea were most common.

Of the 84 patients who had been dosed at last data cut, 7 (8.3%) have experienced serious adverse events, which included vomiting and liver injury. An immune reaction causing inflamed muscles, muscle fatigue and weakness (myositis) was seen in one participant, which was thought to be related to the specific genetic change. Another patient had myocarditis, inflammation of the heart muscle.

Side effects required medical interventions including hospitalizations, but did resolve.
Vomiting, dehydration, nausea, sudden kidney injury from an overactive immune response (atypical hemolytic uremic syndrome-like complement activation), low platelets in the blood (thrombocytopenia).

In early trials, interventions were required including hospitalizations, but all resolved. Steroid dosing was altered to increase dose slightly around the time of gene therapy dosing.

Three serious adverse events, including myocarditis or inflammation of the heart tissue, occurred in CIFFREO. Participants with certain genetic variants could be at higher risk for these adverse events, so exclusion of certain genetic variants was recommended.

A participant in the Phase 2 trial who was non-ambulatory died following administration of the gene therapy. Following this death, the CIFFREO study was placed on hold, which has subsequently been lifted following modification. All possible investigations were undertaken to understand this case and avoid similar future events. The protocol was modified to require that participants be in the hospital for one week after receiving the dose.
SGT-001 Data (no longer in clinical trial)
Vomiting, nausea, sudden kidney injury, thrombocytopenia.

Interventions were required including hospitalizations, but all resolved.

Because of Serious Adverse Events, the study was placed on hold from November of 2019 until October of 2020.

Changes were made to the manufacturing process, and additional medicines (Soliris and a C1 esterase inhibitor) were done before the dose. Inflammatory response seen in one boy after the changes were implemented.

Currently Enrolling Trials

This table includes more information about the clinical trials for these gene therapies, including the trials that are currently enrolling or expected to begin enrollment.

SponsorCurrently enrolling trialParticipant characteristicsGenetic variant exclusionsPrimary EndpointsPlaceboFollow-upTests RequiredSitesFuture studies
SareptaBy invitation:
46 boys
Uses commercially produced product.
20 boys
  • Initial cohort was 4-8th birthday
  • Stable steroids for 12 weeks
  • Antibodies to AAV are not elevated

Also enrolled boys 8-18 who are ambulatory, boys who are non-ambulatory, and boys age 3. Planning to enroll small number of boys who have variants in exons 1-17.
Microdystrophin levels on Western blot at 12 weeks.None5 years
  • Muscle biopsy
  • Physical exams
  • Laboratory testing
  • Cardiac evaluations
United States: CA, MO, OH, VA
ENVISION 303: Planned to be for non-ambulatory and ambulatory 8-17.

Non-Ambulatory (Cohort 1): 120

Ambulatory (Cohort 2): 28
  • Non-ambulatory with no age limits
  • Stable corticosteriods (which may include no steroids) for 12 weeks
  • Antibodies to AAV are not elevated

  • Ages 8 until the 18th birthday
  • Ability to cooperate with motor testing
  • Stable corticosteroids (which may include no steroids) for at least 12 weeks
  • Antibodies to AAV are not elevated
  • Exclusion of variants in exons 1-17
Change in Performance of Upper Limb score (PUL)Yes, 1:1 with a crossover at 72 weeks.124 weeks (nearly 3 years)
  • Laboratory testing
  • Physical evaluations
  • Muscle biopsy for some participants at certain sites
  • Cardiac evaluation
  • Wearable devices
  • Children's Hospital of the King's Daughter, VA
  • Most enrollment to occur outside of the USA

Ambulatory: Will enroll outside of the USA but sites not yet available
GenethonTrial has multiple parts, first is dose finding, second is randomized efficacy.
  • 6-10 years
  • Ambulatory
North Star Ambulatory Assessment (NSAA) scores at 1 year.Yes, in the randomized efficacy part of the study.
  • France
  • England
  • 4-11 years
  • Stable steroids for 12 weeks
  • Antibodies to AAV are not elevated
  • Functional criteria of walk 100 meters and time to stand
  • Impaired heart function
  • Exclusion of variants in exons 1-17
  • Muscle biopsy
  • Laboratory testing
  • Physical evaluations such as NSAA
United States: AR
SolidInspire6 boys
Cohort 1:
  • 4-6th birthday
  • Weight less than 40 lbs
  • Stable daily steroids for 12 weeks
  • Antibodies to AAV are not elevated
Cohort 2: 6-8th birthday
  • Exclusion of deletions in exons 1-11 and exons 42-45, inclusive
SafetyNone5 years
  • Muscle biopsy
  • Physical exams
  • Physical evaluations of motor function
  • Lung function testing
  • At home activity monitoring
United States: CA and OH

Understanding Differences in Gene Therapies

There are currently four companies who have DMD gene therapy products that have been given to boys with Duchenne, and three of the companies have ongoing studies in the USA. A fifth company plans to begin dosing in 2023.

Each of these gene therapies has slight variations in their three main components: the transgene, the promoter, and the vector.

  • The transgene is the DNA sequence that will code for the mini- or micro-dystrophin protein.
  • The promoter is a piece of DNA that tells the body where to turn on production of the transgene. The gene can get into many different tissues, not just the muscle, so we want to ensure the new protein is only produced in tissues where there would be a benefit, such as the skeletal or cardiac muscle.
  • The vector is the transporter for the transgene and promoter to get into the target tissue. In current studies a modified virus called adeno-associated virus or AAV is used. It is a tiny virus with a limited storage capacity, which is why current studies use a micro or mini-dystrophin transgene rather than full length dystrophin instructions. There are different serotypes or versions of the virus such as AAV8, AAV9, AAVrh74 that are being used in trials.

Each company has chosen a different combination of transgene, promoter, and vector. All of the micro/mini-dystrophins are much smaller than the typical dystrophin gene, but are based on dystrophin changes seen in patients with milder cases.

Our Understanding of Current Data

Many families ask us which of these gene therapies is the “best”, and the answer to that is that we do not yet know. Because the gene therapies are in clinical trials, we are still gathering data to understand how well they work and how long they last. These tables were developed as tools to enable families to understand what data is available on the gene therapies so far, as well as the currently enrolling clinical trials.

  • The data that we currently have suggests that the gene therapies, especially at the current higher doses, result in increased expression of the micro/mini-dystrophin and that the increase lasts for at least a year.
  • Current data also shows that most boys who receive the gene therapy will have side effects. For most, the side effects occur soon after the dosing and are manageable with medications such as steroids and other treatment, and in some cases, hospitalizations.
  • We also know that, tragically, one child died after receiving gene therapy. Details regarding what happened for that child are limited.
  • We also do not yet know how well the micro/mini-dystrophins will function as a replacement for standard dystrophin or how long the production of the micro/mini-dystrophin will last.

Considering Gene Therapy Trials

These gene therapies are all still in clinical trials, and each of the trials is set up differently in the criteria to be included and in the procedures that are part of the study. Because all clinical trials have risks and benefits, it is important to discuss any trial you might be considering with your or your child’s medical team. Families often contact us to better understand the different gene therapies and the various clinical trials–we are happy to talk through the various options with you in more detail.

Schedule time with a PPMD Genetic Counselor

Do you have questions about clinical trials? Please reach out to PPMD’s genetic counselors – we are here to help you!