REGENXBIO Doses First Patient in Phase 3 Trial for DMD Gene Therapy RGX-202
The company also announced updated efficacy data from the trial’s phase 1/2 portion.
Aravindhan Veerapandiyan, MD
(Credit: UAMS Health)
REGENXBIO has dosed the first patient in the pivotal phase 3 portion of its phase 1/2/3 AFFINITY DUCHENNE clinical trial (NCT05693142), which is evaluating RGX-202, an investigational adeno-associated virus (AAV) vector-based gene therapy, for the treatment of Duchenne muscular dystrophy (DMD).1
REGENXBIO noted that the phase 3 portion of the trial is utilizing 2×1014 GC/kg, which was dose level 2 (DL2) in the study’s dose expansion portion, as the pivotal dose, in accordance with an End of Phase 2 meeting that the FDA held with the company. Furthermore, REGENXBIO anticipates that it will submit a biologics license application for RGX-202 in 2026 via an accelerated approval pathway. The phase 3 portion, which is expected to enroll around 30 patients with DMD aged 1 and older who are ambulatory, will utilize the proportion of patients who achieve an RGX2-202 microdystrophin expression of at least 10% at 12 weeks posttreatment as its primary end point. The changes from baseline on TTStand, 10MWR, and TTClimb in patients aged 4 years or older will serve as secondary end points. The Peabody Developmental Motor Scale-Third Edition (PDMS-3) and SV95C will be used to assess patients younger than 4 years in the trial. The North Star Ambulatory Assessment (NSAA) will be utilized for an exploratory end point.
Alongside these announcements, REGENXBIO reported 12-month efficacy data from 3 patients aged 4 to 10 years who were treated at dose level 1 (DL1, 1x1014 GC/kg) in the phase 1/2portion and 9-month efficacy data from 2 patients aged 8 to 12 years who were treated at DL2 in the phase 1/2 portion. External natural history controls matched for age and baseline function were used for comparison. REGENXBIO highlighted that stability or improved function on the NSAA and on timed function tests were recorded in all 5 of the treated patients. In addition, the 2 patients who received DL2 achieved an improvement of 5.5 points in mean score on the NSAA at 9 months posttreatment. These patients also showed improvement on timed function tests at the same time point. Their scores on the NSAA and timed function tests were greater than those attained by patients from the natural history control group. REGENXBIO also pointed out that the 3 patients treated at DL1 each showed improvements on timed function tests and the NSAA at 12 months posttreatment. Notably, these patients achieved greater than the minimal clinically important difference benchmark on change in timed task velocity at the 12 month time point. According to REGENXBIO, biomarker data for patients treated in the phase 1/2 portionindicated high and consistent expression and transduction of the microdystrophin transgene and that the gene therapy was localized to the sarcolemma, as intended.
"The initiation of our pivotal trial and newly released positive functional data are exciting milestones on our path to rapidly deliver RGX-202, the only next generation gene therapy in pivotal phase, to the Duchenne community," Curran M. Simpson, the president and chief executive officer of REGENXBIO, said in a statement.1 "The totality of our data demonstrates that RGX-202 provides evidence of improving outcomes for boys with Duchenne and altering the trajectory of this devastating disease, with consistent, robust expression of our novel microdystrophin translating into significant clinical benefit. Based on the strength of the phase 1/2 data and our positive discussions and alignment with the FDA, we are quickly advancing RGX-202 toward a BLA filing in 2026 using the accelerated approval pathway. We continue to evaluate opportunities to expand the RGX-202 program to benefit Duchenne patients worldwide."
REGENXBIO additionally reported safety data from a set of patients that included 3 patients aged 4 to 11 years treeated at DL1, 7 patients aged 4 to 11 years treated at DL2, and 1 patient aged 1 to 3 years who received DL2. In this group, there were no serious adverse events (AEs) and no AEs of special interest, including no cases of central or peripheral neurotoxicity, drug-induced liver injury, or thrombocytopenia. RGX-202 was characterized as “well-tolerated”, with the most common AEs deemed related to the gene therapy being nausea, vomiting, and fatigue. These AEs, which the company pointed out are expected with gene therapy treatment, were noted to have resolved. No cases of myocarditis or myositis were reported.
"There remains a critical need for new therapeutic options for patients with DMD", Aravindhan Veerapandiyan, MD, of Arkansas Children's Hospital, added to the statement.1 "I am very pleased to see the advancement of the RGX-202 program to the pivotal stage, which offers promise for a broader patient population and am highly encouraged by the functional data presented today demonstrating RGX-202's potential to alter the course of the disease. The safety, functional, and biomarker data shared today reinforce the positive feedback from families, highlighting improvements in patients' daily activities and underscoring the potential benefits of this treatment."
Earlier this year, in June, REGENXBIO announced that it had started enrollment for a new cohort of younger patients in the phase 1/2portion of AFFINITY DUCHENNE.2 The new cohort, which is open to ambulatory boys with DMD, will seek to enroll up to 5 participants aged 1 to 3 years old for treatment at DL2. REGENXBIO expects that the 12 patients treated at DL2 in AFFINITY DUCHENNE will be part of the data set that supports the planned BLA.
"With the wider adoption of newborn screening, there is now an increased opportunity to treat patients earlier, with the hope of impacting disease and preserving muscle,” trial investigator Vamshi K. Rao, MD, of Lurie Children's Hospital, who is also an associate professor of pediatrics at Northwestern University Feinberg School of Medicine, said in a June 2024 statement.2 RGX-202 was previously granted fast track designation by the FDA in April 2023, orphan drug designation from the agency in November 2021, and rare pediatric disease designation in March 2022.3-5
