Phase 1/2 AFFINITY DUCHENNE Trial Expands to Include Younger Cohort of Duchenne Muscular Dystrophy


The newly added cohort allows for greater opportunity to treat patients earlier, with the hope of impacting disease course and preserving muscle.

Curran Simpson, chief operating officer, president, and chief executive officer-select at REGENXBIO

Curran Simpson

According to a recent announcement, REGENXBIO has initiated enrollment in a new cohort of patients aged 1-3 in its phase 1/2 AFFINITY DUCHENNE trial (NCT05693142) to assess the safety and efficacy of RGX-202, an investigational gene therapy, in boys with Duchenne muscular dystrophy (DMD). The company expects to announce initial strength and functional assessment data for both dose levels of the trial in the second half of 2024.1

The trial, a multicenter, open-label, dose escalation and dose expansion study, is now enrolling ambulatory boys with DMD aged 1 to 11, including 5 aged 1-3. Those younger, newly added patients will receive RGX-202 at the pivotal dose level (2 x 1014 genome copies/kg body weight). In addition, the company noted they it continues to enroll the remaining patients in the ages 4-11 cohort and expects to imminently complete the enrollment of up to 7 patients at dose level 2 early third quarter of 2024.

RGX-202, an adeno-associated virus (AAV) vector-based gene therapy, is intended to deliver a novel transgene which contains the functional elements of the C-Terminal (CT) domain seen in natural dystrophin. Presence of the CT domain has been shown in preclinical studies to recruit several key proteins to the muscle cell membrane, leading to improved muscle resistance to contraction-induced muscle damage in dystrophic mice.

"We believe RGX-202 has unique, differentiating features that support its potential to be a best-in-class product and we are pleased to expand its clinical development to reach a wider range of boys with Duchenne in need of treatment options,” Curran Simpson, chief operating officer, president, and chief executive officer-select at REGENXBIO, said in a statement.1 "Supported by the strong safety profile and positive microdystrophin data demonstrated in the AFFINITY DUCHENNE trial, today's news marks significant steps in rapidly accelerating RGX-202 towards pivotal stage and future commercialization."

As part of its announcement, the company noted that it anticipates all patients enrolled at dose level 2 (n = 12) to be included in its pivotal trial data set. The company will meet with the FDA at the end of July for an end-of-phase 2 meeting, where they will discuss using microdystrophin expression of RGX-202 as a surrogate end point to support a biologics license application submission.

READ MORE: FDA Grants Traditional Approval to Elevidys Gene Therapy for Ambulatory DMD, Accelerated Approval for Nonambulatory Patients

RGX-202, which is being tested in those with DMD gene mutations in exons 18 and above, will seek approval through the accelerated approval pathway once ready. Initiation of the pivotal study, which will comprise all data sets from all ages, is on track for late third quarter to early fourth quarter of 2024. As of May 3, 2024, the therapy has been well tolerated with no drug-related serious adverse events (AEs) in 5 patients, aged 4.4 to 12.1. To date, all 5 patients who completed 3-month trial assessments indicated “encouraging” increases in expression of RGX-202 microdystrophin and reduction from baseline in serum creatine kinase levels, supporting evidence of clinical improvement.

"The Duchenne community remains in need of differentiated treatment options, and I'm pleased to see the expansion of the AFFINITY DUCHENNE trial to evaluate RGX-202 in younger patients,” trial investigator Vamshi Rao, MD, associate professor of pediatrics at the Northwestern University Feinberg School of Medicine, said in a statement.1 "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."

At the 2023 Annual International Congress of the World Muscle Society, preliminary data from a few patients in the trial were presented. In a patient aged 4.4 years old, treatment with RGX-202 resulted in microdystrophin expression of 38.8% in comparison with control, as well as a 43% reduction in CK levels at 10 weeks. Using the same dosage, a patient aged 10.6 years old had 11.1% of RGX-202 microdystrophin expression compared with the control and reported a 44% reduction from baseline in serum CK levels at 10 weeks. The therapy was well tolerated, with no therapeutic-related serious AEs in 3 patients, aged 4.4, 10.6, and 6.3 years, dosed at the level 1 dosage.2

The initial biomarker data from those 2 patients indicated an increase in expression of microdystrophin from bicep muscle biopsies taken at 3 months following a one-time administration of RGX-202. Notably, RGX-202 microdystrophin was detected by immunofluorescence staining throughout muscle tissue at 3 months, with the microdystrophin protein localized to the sarcolemma.

Following this data, Aravindhan Veerapandiyan, MD, a pediatric neuromuscular neurologist at Arkansas Children’s Hospital and associate professor of pediatrics at the University of Arkansas for Medical Sciences, sat down to provide an overview of the results. In the link below, he discussed the initial data on those 3 patients, and the impacts of RGX-202 on dystrophin expression and serum creatine kinase levels.

1. REGENEXBIO announces expansion of AFFINITY DUCHENNE trial to include a new cohort of younger patients. News release. June 24, 2024. Accessed June 27, 2024.
2. REGENXBIO Presents Interim Clinical Data from Phase I/II AFFINITY DUCHENNE™ Trial of RGX-202 at 28th Annual International Congress of the World Muscle Society. News Release. REGENXBIO. Published October 3, 2023. Accessed June 27, 2024.
Related Videos
Emma Ciafaloni, MD, an expert on Duchenne muscular dystrophy
Emma Ciafaloni, MD, an expert on Duchenne muscular dystrophy
Charbel Moussa, MBBS, PhD
4 KOLs are featured in this series.
4 KOLs are featured in this series.
4 KOLs are featured in this series.
5 KOLs are featured in this series.
5 KOLs are featured in this series.
Debra Miller
Charbel Moussa, MBBS, PhD
© 2024 MJH Life Sciences

All rights reserved.