May 17, 2025 – GenAssist Ltd (GenAssist) today announced updated efficacy results—highlighting new biomarker findings—from its ongoing investigator-initiated trial (IIT) of GEN6050X. The latest data were presented orally in the Gene Therapy for Muscle diseases session at the 28th Annual Meeting of the American Society of Gene & Cell Therapy.
GEN6050X is an investigational base editing drug for Duchenne Muscular Dystrophy (DMD), which targets patients amenable to exon 50 skipping. The action mechanism of GEN6050X includes base editor-mediated exon skipping to restore dystrophin expression and ACTG1 overexpression to enhance the cytoskeleton and improve muscle function.
The IIT study is being conducted at Peking Union Medical College Hospital (NCT06392724) since August 2024. Until now, two patients (10 yrs and 6.5 yrs) have been dosed and finished six months of follow-up. The third patient will be dosed in June. All patients in the study received a dose of 5×10¹³ vg/kg. GEN6050X received FDA IND approval on March 6, 2025, which is the first gene editing drug IND approved by FDA for DMD.
Key Highlights of the Report
- 6-Month Efficacy Data update
- Biomarker
In the muscle biopsy of the second patient, 1.60% DNA editing efficiency and 2.17% exon 50 skipping were observed. Dystrophin protein in muscle biopsies increased to 2.9 times the baseline level.
For the first patient, the editing efficiency, exon skipping and dystrophin protein have not been detected likely due to high fat content in the muscle biopsy sample. Method optimization is currently underway, and reanalysis is planned.
- Behavior Assessment
In the six-month interim assessment of the first two patients, GEN6050X demonstrated encouraging improvements in the North Star Ambulatory Assessment (NSAA) as well as the Performance of Upper Limb scale 2.0 (PUL2.0). Both patients also showed improved cardiac function, as evidenced by increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) following treatment. For the first patient, who has already developed dilated cardiomyopathy, the two parameters have recovered to normal range 6 months after treatment.
Table Summary of motor and cardiac function assessment
* The lower limit of normal and LVEF and LVSF is 50% and 29%, respectively.
Additionally, Hand-held dynamometer (HHD) was used to measure the upper and lower limb strength. Patient1 kept stable in elbow and knee strength (-26% to +18%) in HHD test. The second patient revealed an increasing trend in upper and lower limb strength, especially in elbow strength (11% to 50%).
- Safety Profile update
GEN6050X demonstrated a favorable safety profile with only transient and manageable serious adverse events during two-week inpatient period. To date, follow-up evaluations have revealed no clinically significant symptoms or laboratory abnormalities in either patient.
In addition, immunogenicity testing of GEN6050X revealed no detectable anti-Cas9 IgG antibodies and no T cell responses against AAV9, transgene, or dystrophin protein.
“These encouraging biomarker and functional results highlight the unique mechanism of action of GEN6050X. Unlike other modalities targeting DMD gene, GEN6050X demonstrates significant clinical benefit even with relatively low levels of dystrophin restoration in skeletal muscle. Assumed that humans have similar biodistribution of GEN6050X as nonhuman primates (5-15 times in heart than skeletal muscles), higher vector distribution in heart may result in more dystrophin protein restoration than skeletal muscles. As the center of circulation system, dystrophin restoration in cardiomyocytes at an early age can effectively enhance cardiac function, which finally contributes to the observed motor function improvement.” said Dr. Chunyan He, CEO of GenAssist. “These findings underscore the potential of GEN6050X as a transformative base editing therapy for DMD and point toward a shift in treatment strategy that places greater emphasis on cardiac outcomes.”
