Regenxbio reported additional positive interim data from Cohorts 4 and 5 of its RGX-314 phase 1/2a trial for the treatment of wet age-related macular degeneration (AMD), and Cohort 3 of its Long-Term Follow-Up (LTFU) study. RGX-314 is a potential best-in-class, one-time gene therapy for the treatment of wet AMD. The data were presented at the Angiogenesis, Exudation, and Degeneration 2021 conference.
“The continued durability of treatment effect up to 3 years after RGX-314 administration highlights the potential of RGX-314 as a one-time treatment option for patients with wet AMD. The results from the phase 1/2a trial of RGX-314 using subretinal delivery have informed the key design elements of our pivotal program, in which we plan to conduct two randomized, well-controlled clinical trials, enrolling approximately 700 patients total” Steve Pakola, MD, Chief Medical Officer of Regenxbio, said in a company news release.
“I am excited about this data out to 3 years, which demonstrates that one-time treatment with RGX-314 has the potential to result in long-term stability to improvement of visual acuity outcomes and retinal anatomy, while alleviating treatment burden,” Allen C. Ho, MD, Director of Retina Research at Wills Eye Hospital and Mid Atlantic Retina and investigator surgeon in the RGX-314 clinical trials, said in the news release. “In our practice, and as reported by multiple real-world studies, we see many patients losing vision due to lack of compliance with standard of care, which requires frequent anti-VEGF injections. I look forward to further evaluating the effects of RGX-314 in ATMOSPHERE, the first pivotal trial of a gene therapy for the treatment of wet AMD.”
Study Design and Safety Update from Phase 1/2a Trial of RGX-314 for the Treatment of Wet AMD Using Subretinal Delivery
In the phase 1/2a trial of RGX-314, 42 patients with severe wet AMD requiring frequent anti-vascular endothelial growth factor (anti-VEGF) injections were treated across five dose cohorts, with doses ranging from 3×109 GC/eye to 2.5×1011 GC/eye.
As of January 22, 2021, RGX-314 continued to be generally well-tolerated across all cohorts, with 20 serious adverse events (SAEs) reported in 13 patients, including one possibly drug-related SAE of significant decrease in vision in Cohort 5. The most common nonserious adverse events in the eye were generally assessed as mild (87%). These included postoperative conjunctival hemorrhage (69% of patients), postoperative inflammation (36% of patients), eye irritation (17% of patients), eye pain (17% of patients), and postoperative visual acuity reduction (17% of patients). In 67% of patients across all cohorts, and in 83% of patients in Cohorts 3 through 5, retinal pigmentary changes were observed on imaging, the majority of which were in the peripheral inferior retina. Retinal hemorrhage was observed in 26% of patients and is an anticipated event in patients with severe wet AMD. There have been no reports of clinically-determined immune responses, drug-related ocular inflammation, or post-surgical inflammation beyond what is expected following routine vitrectomy.
Summary of Data for Cohorts 4 and 5
Today’s update includes data from Cohorts 4 and 5 as of January 22, 2021. Each cohort enrolled 12 patients each at doses of 1.6×1011 GC/eye and 2.5×1011 GC/eye, respectively.
Patients in Cohorts 4 and 5 at 1.5 years after administration of RGX-314 demonstrated stable visual acuity with a mean Best Corrected Visual Acuity (BCVA) change of +1 letters and -1 letters from baseline, respectively, as well as decreased central retinal thickness (CRT), with a mean change of -46 µm and -93 µm, respectively.
There was a meaningful reduction in anti-VEGF treatment burden in both Cohorts 4 and 5 compared to the mean annualized injection rate during the 12 months prior to RGX-314 administration. Patients in Cohort 4 received a mean of 4.4 injections over 1.5 years following administration of RGX-314, a 58.3% reduction in anti-VEGF treatment burden. Patients in Cohort 5 received a mean of 1.7 injections over 1.5 years following administration of RGX-314, a reduction in anti-VEGF treatment burden of 81.2%.
In Cohort 4, four out of 12 (33%) patients have received no anti-VEGF injections after 6 months following RGX-314 administration and demonstrated a mean BCVA change from baseline of +2 letters at 1.5 years. Eight out of 11 (73%) patients have received no anti-VEGF injections after 6 months following RGX-314 administration and demonstrated a mean BCVA change from baseline of -2 letters at 1.5 years.
Summary of Long-Term Follow-Up (LTFU) Study Data
Following the phase 1/2a trial, patients are encouraged to enroll in a LTFU study to assess safety and efficacy up to 5 years after RGX-314 administration. Patients in the LTFU study have scheduled visits every 6 months for the first year and then annual visits until the end of the study. Patient management is per physician discretion. Data collected during the scheduled study visits include safety, BCVA, and CRT. In addition, chart reviews are conducted at each scheduled study visit to collect the number of retina specialist visits and anti-VEGF injections each patient has received since the prior scheduled study visit.
As of January 22, 2021, RGX-314 continued to be generally well-tolerated in patients enrolled in the LTFU study, with no new drug-related ocular adverse events reported.
All six patients from Cohort 3 of the phase 1/2a trial enrolled in the LTFU study, and long-term treatment effect was demonstrated over 3 years. These patients demonstrated a mean BCVA improvement of +12 letters from baseline at 3 years. Retinal anatomy as measured by machine-read CRT remained stable at three years compared to the 2-year timepoint.
Patients also demonstrated long-term reductions in anti-VEGF treatment burden over 3 years with a mean annualized rate of 2.4 anti-VEGF injections after administration of RGX-314, which is a reduction of 66.7% from the mean annualized injection rate during the 12 months prior to administration of RGX-314. Three out of six (50%) patients received no anti-VEGF injections over 3 years following one-time administration of RGX-314. Four out of six (67%) patients have received no anti-VEGF injections from 9 months to 3 years after RGX-314 administration. The four patients who did not receive anti-VEGF injections after 9 months demonstrated a mean BCVA improvement from baseline of +11 letters at 3 years.