Benzinga | Feb 16, 2021 07:11AM EST

REGENXBIO Announces Additional Interim Phase I/IIa And Long-Term Follow-Up Data Of RGX-314 For Wet AMD

* RGX-314 using subretinal delivery continues to be generally well-tolerated at all dose levels

* Positive interim update from Cohorts 4 and 5 at 1.5 years after RGX-314 administration Durable treatment effect observed with stable visual acuity, decreased retinal thickness, and reductions in anti-VEGF injection burden

* Long-term, durable treatment effect over three years demonstrated in Cohort 3 Mean improvement in vision and stable retinal thickness 50% of patients (3/6) remain anti-VEGF injection-free over three years; 67% of patients (4/6) are anti-VEGF injection-free from nine months to three years

* ATMOSPHERE(tm), the first of two planned pivotal trials for RGX-314, is active and enrolling

REGENXBIO Inc. (NASDAQ:RGNX) reported at the Angiogenesis, Exudation, and Degeneration 2021 conference additional positive interim data from Cohorts 4 and 5 of its RGX-314 Phase I/IIa trial for the treatment of wet age-related macular degeneration (wet 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 continued durability of treatment effect up to three 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 I/IIa 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," said Steve Pakola, M.D., Chief Medical Officer of REGENXBIO.

"I am excited about this data out to three 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," said Allen C. Ho, M.D., Director of Retina Research at Wills Eye Hospital and Mid Atlantic Retina and investigator surgeon in the RGX-314 clinical trials. "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 ATMOSPHERETM, the first pivotal trial of a gene therapy for the treatment of wet AMD."

Study Design and Safety Update from Phase I/IIa Trial of RGX-314 for the Treatment of Wet AMD Using Subretinal Delivery

In the Phase I/IIa 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 3x109 GC/eye to 2.5x1011 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 post-operative conjunctival hemorrhage (69% of patients), post-operative inflammation (36% of patients), eye irritation (17% of patients), eye pain (17% of patients), and post-operative 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 1.6x1011 GC/eye and 2.5x1011 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 ?m and -93 ?m, 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 six months following RGX-314 administration and demonstrated a mean BCVA change from baseline of +2 letters at 1.5 years. Eightout of 11 (73%) patients have received no anti-VEGF injections after six 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 I/IIa trial, patients are encouraged to enroll in a LTFU study to assess safety and efficacy up to five years after RGX-314 administration. Patients in the LTFU study have scheduled visits every six 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 I/IIa trial enrolled in the LTFU study, and long-term treatment effect was demonstrated over three years. These patients demonstrated a mean BCVA improvement of +12 letters from baseline at three years. Retinal anatomy as measured by machine-read CRT remained stable at three years compared to the two-year timepoint.

Patients also demonstrated long-term reductions in anti-VEGF treatment burden over three 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 three years following one-time administration of RGX-314. Four out of six (67%) patients have received no anti-VEGF injections from nine months to three years after RGX-314 administration. The four patients who did not receive anti-VEGF injections after nine months demonstrated a mean BCVA improvement from baseline of +11 letters at three years.