Wet AMD Gene Therapy Trial Demonstrates Consistent Safety and Efficacy With New Manufacturing Process

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No serious adverse events deemed related to RGX-314 occurred in the treated patients.

REGENXBIO’s RGX-314, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat wet age-related macular degeneration (AMD), has demonstrated consistent results between product manufactured with the company’s new NAVXpress bioreactor platform process and product produced with an adherent cell culture process.1

RGX-314, which is being developed in collaboration with AbbVie, is delivered via REGENXBIO’s NAV AAV8 vector. It encodes for an antibody fragment meant to inhibit the vascular endothelial growth factor (VEGF) pathway that causes leaky blood vessels to grow in patients with wet AMD. The interim data, from a phase 2 bridging study (NCT04832724), were presented at the Angiogenesis, Exudation, and Degeneration 2023 Conference. The trial administered RGX-314 to participants with wet AMD at doses of either 6.4x1010 GC/eye or 1.3x1011 GC/eye. In each dose level group, half of the patients received RGX-314 produced via the NAVXpress platform process while the other half received RGX-314 produced by the adherent cell culture manufacturing process previously used in a phase 1/2a clinical trial for RGX-314 (NCT03066258).

The company has announced that RGX-314 was well-tolerated in 46 participants who have been dosed across the bridging study’s cohorts as of the November 14, 2022, data cutoff. There were 5 serious adverse events (AEs) reported, however none were deemed related to the gene therapy. It was noted that in the high dose cohorts, all common AEs in the study eye were mild to moderate through 6 months post-treatment. Common AEs included post-operative conjunctival hemorrhage, post-operative inflammation, and retinal pigmentary changes.

In terms of efficacy measures, it was reported that for the 30 patients in the high dose cohorts, which have been fully enrolled and completed 6 months of follow-up, target protein concentrations in the eye were similar between patients treated with either manufacturing process. Furthermore, patients treated in both of the high dose cohorts showed stable to improved best corrected visual acuity (BCVA) and central retinal thickness (CRT). Additionally, meaningful decreases in anti-VEGF treatment burden were observed in these patients, with the majority of the patients not requiring supplemental anti-VEGF injections.

"There is a significant need for treatment options that can reduce the burden of frequent injections for wet AMD patients while maintaining optimal function and anatomic outcomes," Charles C. Wykoff MD, PhD, director of research at Retina Consultants of Texas; chairman of research, Retina Consultants of America; and deputy chair of Ophthalmology for the Blanton Eye Institute, Houston Methodist Hospital, who presented the data, said in a statement.1 "The clinical profile of RGX-314 manufactured using the commercial-scale process is encouraging, as is the potential of a one-time therapy for the treatment of wet AMD."

RGX-314 is also being evaluated for the treatment of wet AMD in 2 multicenter, randomized, active-controlled pivotal trials, the phase 2b/3 ATMOSPHERE study (NCT04704921) and the phase 3 ASCENT study (NCT05407636). REGENXBIO has incorporated material produced via the NAVXpress platform process into these trials. Both trials will use the same 2 doses from the phase 2 bridging study and will evaluate RGX-314 against the standard of care for wet AMD. The company anticipates that the results of these trials will support a biologics license application submission currently planned for 2024.

In addition to wet AMD, RGX-314 is also being evaluated for the treatment of diabetic retinopathy (DR) and other retinal indications. Data from the phase 1/2 ALTITUDE study (NCT04567550), which is evaluating RGX-314 for the treatment of DR, were presented late last year at the 55th Annual Retina Society (ARS) meeting in Pasadena, California.2 The data showed clinically meaningful improvements in the Early Treatment DR Study-DR Severity Scale (DRSS) for patients treated with RGX-314 in the trial’s first 3 cohorts compared to patients treated with a control.2 It was additionally noted that RGX-314 was well-tolerated in the 50 patients treated in these cohorts. RGX-314 is also being evaluated for the treatment of wet AMD in a separate phase 2 clinical trial (AAVIATE; NCT04514653) which is utilizing a suprachoroidal delivery method rather than the subretinal method used in the bridging study.1

"The interim results observed in the phase 2 bridging study show a similar clinical profile between our manufacturing processes,” Curran Simpson, chief operating officer, REGENXBIO, added to the statement.1 “We believe our approach, focused on early product quality and process control, allows us to efficiently transition from clinical trials to commercial readiness. This update provides validation of our plans for the NAVXpress platform process to support the production of RGX-314 in anticipation of future commercialization."

REFERENCES
1. REGENXBIO presents interim data from phase II bridging study evaluating the clinical performance of RGX-314 using the NAVXpress manufacturing platform process. News release. REGENXBIO Inc. February 11, 2023. Accessed February 13, 2023. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-presents-interim-data-phase-ii-bridging-study 
2. Vajzovic L. Suprachoroidal Delivery of RGX-314 for Diabetic Retinopathy Without CI-DME: The Phase II ALTITUDE Study. Presented at: 55th ARS meeting, Pasadena, CA, November 2-5, 2022.
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