The 2 companies advancing the concept of a single-injection, gene-derived anti-VEGF therapy for wet AMD both continue to report positive early-stage results. Adverum Biotechnologies reported that all 6 of the patients in the first cohort of its OPTIC phase 1 trial for ADVM-022 (aflibercept) have gone more than a year without needing a rescue injection, with some now out to 66 weeks. Regenxbio reported improved mean BCVA over a larger patient base with its RGX-314 (ranibizumab), although some patients did require rescue injections.

For RGX-314, positive long-term efficacy signals continued over 2 years in the 6-patient cohort 3. The mean change in visual acuity across all 6 patients in Cohort 3 was markedly improved over 2 years, with a mean BCVA improvement of +14 letters. The mean change in CRT was stable, with an increase of +2 microns.
Patients in cohort 3 also demonstrated long-term reductions in anti-VEGF treatment burden over 2 years, with a mean annualized rate of 2.8 anti-VEGF injections after administration of RGX-314, a reduction of more than 60% from the mean annualized injection rate during the 12 months prior to administration of RGX-314. Three out of 6 (50%) patients received no anti-VEGF injections over 2 years following one-time administration of RGX-314.

Although no new efficacy information for 12-patient cohort 4 was provided, patients in cohort 5 continued to demonstrate a meaningful reduction in anti-VEGF treatment burden over 9 months following administration of RGX-314, with 8/11 (73%) patients remaining anti-VEGF injection-free, and a reduction across the cohort of more than 80% from the mean annualized injection rate during the 12 months prior to RGX-314 administration.
"I am impressed by the overall outcomes in patients after a one-time administration of RGX-314. I believe that RGX-314 is the leading gene therapy program for a major retinal disease such as wet AMD and could be an important potential one-time treatment option for AMD," said Allen C. Ho, MD, Director of Retina Research at Wills Eye Hospital and Mid Atlantic Retina and investigator surgeon in the RGX-314 trial, on a company call.        

Peter Campochiaro, MD, of the Wilmer Eye Institute, noted that each patient is different and there are fluid variabilities that aren't captured on monthly OCT. He said higher doses could mean that all patient variability is captured. Higher dose seems to correlate with fewer injections needed, as has been noted in cohort 5, he asserted. As of April 6, 2020, RGX-314 continued to be well-tolerated across all cohorts, with no drug-related serious adverse events (SAEs) reported. 

Adverum announced new interim clinical data from cohorts 1-3 of the OPTIC phase 1 dose-ranging clinical trial of ADVM-022 intravitreal (IVT) injection gene therapy in patients requiring frequent anti-VEGF injections for their wet AMD. Initial interim data were presented on a company call from 5 patients in the 9-patient cohort 3 and updated data presented from cohorts 1 and 2 following treatment with a single IVT injection of ADVM-022.
ADVM-022 continues to show robust efficacy, with evidence of a dose response. In the higher-dose cohort 1, 6 of 6 patients have stayed rescue injection free. In the lower-dose cohorts 2 and 3, 8 of 11 patients remain rescue injection free.

ADVM-022 continues to be well tolerated with a favorable safety profile in all 3 cohorts, with related ocular AEs mild (69%) to moderate (31%). There was no evidence of vasculitis, retinitis, or choroiditis. Ocular inflammation, when observed, has been responsive to steroid eye drops. Early evidence from cohort 3 suggests that a 6-week prophylactic regimen of steroid eye drops results in fewer adverse events and less inflammation, compared to a 13-day prophylactic regimen of oral steroids as used in cohorts 1 and 2. In all 9 patients in cohort 3, no cellular inflammation graded at a score above 1+ in any patient.

Early anatomic and vision improvements were observed in cohort 3, with the first 5 patients with 20 weeks follow-up showing a mean CRT reduction of -137.8 microns and mean BCVA gain of +6.8 letters. Arshad M. Khanani, MD, MA, director of clinical research, Sierra Eye Associates and principal investigator in the OPTIC trial said, “It’s impressive to see the long-term durability demonstrated at the higher dose of ADVM-022 in a patient population that previously required frequent injections to maintain their vision and are now beyond one year of follow-up with no rescue injections. Additionally, preliminary evidence in Cohort 3 shows vision and anatomical improvements and that the 6-week prophylactic steroid eye drop regimen is effective at minimizing early ocular inflammation.”