REGENXBIO Set to Evaluate Duchenne Muscular Dystrophy Gene Therapy RGX-202 in Patients Aged 1 to 3 Years Old

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The company has begun enrolling participants in a new cohort for younger patients in the phase 1/2 AFFINITY DUCHENNE clinical trial.

REGENXBIO has begun enrolling participants for a new cohort of younger patients in the phase 1/2 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

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. All patients will be treated with 2x1014 genome copies (GC)/kg body weight (dose level 2, DL2) of RGX-202, the same dose level that the company plans to use in a future pivotal trial for the gene therapy. Alongside the announcement of enrollment beginning the new cohort enrollment, REGENXIBIO stated that it will be holding an end-of-Phase II meeting with the FDA, in which it plans to finalize design plans for the aforementioned pivotal trial. REGENXBIO expects that the 12 patients treated at DL2 in AFFINITY DUCHENNE will be part of the data set that supports the planned biologics license application (BLA), for which the FDA has confirmed that using an accelerated approval pathway will be viable. Furthermore, the company noted that it intends to use expression of the novel microdystrophin transgene that RGX-202 codes for as a surrogate end point for the BLA submission. REGENXBIO anticipates that the pivotal trial will begin around the transition of Q3 to Q4 in 2024.

"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 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 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."

REGENXBIO noted that it is also actively enrolling patients aged 4 to 11 years for the DL2 expansion cohort in AFFINITY DUCHENNE and that up to 7 new patients are expected to have been enrolled in this cohort by early Q3. The company also stated that initial data covering strength and functional assessments from patients treated at DL1 (1×1014 gc/kg) and DL2 in the trial are expected to be reported before the end of the year.

RGX-202 uses REGENXBIO’s proprietary NAV AAV8 vector and is intended to deliver a novel transgene which contains the functional elements of the C-Terminal (CT) domain seen in natural dystrophin.2 The company has noted that the CT domain's presence “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.”2

Data from 4 patients treated in AFFINITY DUCHENNE was previously presented at the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, CO.3 The data came from 3 patients treated at DL1 and 1 treated at DL2 and had a February 28, 2024, cutoff date. Microdystrophin expression at the 3-month mark was deemed “robust” at both dose levels by the investigators, with levels of 38.8%, 83.4%, and 11.1% among those aged 4 to 5 years (Patient 1, age 4.4 years), 6 to 7 years (Patient 3, age 6.6 years), and 8 to 11 years at screening (Patient 2, age 10.5 years) compared with control, respectively, for those who received the lower dose. Among the 1 patient with follow-up who received the higher dose (8 to 11 years group), the expression was 75.7% compared with control levels.

In terms of safety, REGENXBIO has stated that as of May 3, 2024, no serious adverse events related to RGX-202 have occurred in 5 treated patients.1 The company characterizes the the gene therapy as “well-tolerated” in these participants, who are 4.4 to 12.1 years of age.

"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, the chief operating officer of REGENXBIO and the president and CEO-elect of the company, added to the 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."

RGX-202 was previously granted fast track designation by the FDA in April 2023.4 It also received orphan drug designation from the agency in November 2021 and rare pediatric disease designation in March 2022.5,6

REFERENCES
1. REGENXBIO announces expansion of AFFINITY DUCHENNE trial to include a new cohort of younger Patients. News release. REGENXBIO Inc. June 24, 2024. Accessed June 26, 2024. https://ir.regenxbio.com/news-releases/news-release-details/regenxbio-announces-expansion-affinity-duchenner-trial-include
2. REGENXBIO announces phase I/II trial of RGX-202, a novel gene therapy candidate for Duchenne muscular dystrophy, is active and recruiting patients. News release. REGENXBIO Inc. January 23, 2023. Accessed June 26, 2024. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-announces-phase-iii-trial-rgx-202-novel-gene-therapy
3. Veerapandiyan A. RGX-202, an Investigational Gene Therapy for the Treatment of Duchenne Muscular Dystrophy: Interim Clinical Data. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO.
4. REGENXBIO receives FDA fast track designation for RGX-202, a novel gene therapy candidate for the treatment of Duchenne muscular dystrophy. News release. REGENXBIO Inc. April 11, 2023. Accessed June 26, 2024. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-receives-fda-fast-track-designation-rgx-202-novel-gene
5. REGENXBIO announces orphan drug designation granted to RGX-202, a novel gene therapy candidate for the treatment of Duchenne muscular dystrophy. News release. REGENXBIO Inc. November 22, 2021. Accessed June 26, 2024. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-announces-orphan-drug-designation-granted-rgx-202
6. REGENXBIO reports fourth quarter and full-year 2021 financial results and recent operational highlights. News release. REGENXBIO Inc. March 1, 2023. Accessed June 26, 2024. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-reports-fourth-quarter-and-full-year-2021-financial
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