Duchenne Muscular Dystrophy Gene Therapy RGX-202 Granted FDA Fast Track Designation

REGENXBIO’s RGX-202, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat Duchenne muscular dystrophy (DMD), has received fast track designation from the FDA.¹

RGX-202 is currently being evaluated in the phase 1/2 AFFINITY DUCHENNE clinical trial (NCT05693142), which is actively recruiting patients with DMD. The company expects to report its initial findings from the study in the second half of 2023. In addition to the fast track designation, the FDA previously granted RGX-202 orphan drug designation in November 2021 and rare pediatric disease designation in March 2022.^2,3

"We are pleased that the FDA has granted fast track designation for RGX-202," Debra Miller, the founder and CEO of CureDuchenne, said in a statement.¹ "Accelerating the development of medicines for Duchenne, especially potential one-time gene therapies like RGX-202, is critical for this community."

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. 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.”

Although the investigational new drug application for the AFFINITY DUCHENNE trial was cleared by the FDA in January 2022, the trial’s initiation was delayed until January 2023 due to an “unexpected and isolated observation” that occurred during the vial-filling stage of the manufacturing process at a third-party manufacturing facility.^4-6 REGENXBIO has announced that it has now manufactured additional commercial-scale cGMP RGX-202 product for use in the AFFINITY DUCHENNE trial at its in-house manufacturing facility, the REGENXBIO Manufacturing Innovation Center, which is located in Rockville, Maryland.¹

In addition to the AFFINITY DUCHENNE trial, REGENXBIO is also carrying out AFFINITY BEYOND (NCT05683379), an observational study assessing the prevalence of AAV8 antibodies in boys aged 12 years or younger with DMD. Patients who enroll in the study will receive a phone or video interview in which they will provide consent and medical history information, a home health visit for the purpose of collecting a blood sample for antibody testing, and a follow-up phone or video call for relay of the antibody test results. The findings from this study may be used to identify patients who are eligible to participate in AFFINITY DUCHENNE or other future trials evaluating RGX-202.

"Fast track designation, along with our capabilities to conduct our clinical trials using commercial-scale cGMP material, will further support the efficient development of RGX-202 from clinic to commercial readiness," Kenneth T. Mills, the president and CEO of REGENXBIO, said in a statement.¹ "RGX-202 is a key part of our '5x25' strategy, and we look forward to continuing to work closely with the FDA and the Duchenne community as we advance a highly differentiated product candidate developed with the potential to make a meaningful difference for patients. We look forward to reporting initial data from our clinical trial of RGX-202 in the second half of this year."

RGX-202 is not the only gene therapy currently in development for DMD. With Sarepta Therapeutics’ biologics license application (BLA) for SRP-9001 set for review by May 29, 2023, there has been a large amount of discussion around DMD gene therapies among neuromuscular disease experts.⁷ CGTLive™ spoke to several experts about the topic at the 2023 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, March 19-22, in Dallas, Texas. Among these were Kevin Flanigan, MD, Director of the Center for Gene Therapy at Nationwide Children's Hospital, who spoke about the importance of doing earlier genetic testing to identify patients with DMD who could potentially receive gene therapies and Rita Perlingeiro, PhD, the Lillehei professor in stem cell and regenerative cardiovascular medicine, Department of Medicine, University of Minnesota, who discussed the use of iPS cell models to study disease pathogenesis in DMD.

REFERENCES

1. 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 April 11, 2023. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-receives-fda-fast-track-designation-rgx-202-novel-gene

2. 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 April 11, 2023. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-announces-orphan-drug-designation-granted-rgx-202

3. REGENXBIO reports fourth quarter and full-year 2021 financial results and recent operational highlights. News release. REGENXBIO Inc. March 1, 2023. Accessed April 11, 2023. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-reports-fourth-quarter-and-full-year-2021-financial

4. REGENXBIO reports first quarter 2022 financial results and recent operational highlights. News release. REGENXBIO. May 4, 2022. Accessed April 11, 2023. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-reports-first-quarter-2022-financial-results-and

5. 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 April 11, 2023. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-announces-phase-iii-trial-rgx-202-novel-gene-therapy

6. REGENXBIO announces FDA clearance of IND for clinical trial of RGX-202, a novel gene therapy candidate for Duchenne muscular dystrophy. News release. REGENXBIO. January 6, 2022. Accessed April 11, 2023. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-announces-fda-clearance-ind-clinical-trial-rgx-202

7. Sarepta Therapeutics announces advisory committee meeting will be held for SRP-9001. News release. Sarepta Therapeutics. March 16, 2023. Accessed April 11, 2023. https://www.businesswire.com/news/home/20230316005693/en