May 31, 2019 Conference
Gene therapy delivering a transgene for an anti-VEGF protein has the potential for continuous anti-VEGF therapy after a one- time subretinal administration. The RGX-314 Phase I/IIa study is underway to evaluate the safety and signals of efficacy of an AAV8 vector encoding for a soluble anti-VEGF Fab protein, in previously-treated for nAMD subjects.
Phase I/IIa trial is evaluating five doses of RGX-314 (3 x 109, 1 x 1010, 6 x 1010, 1.6 x 1011, and 2.5 x 1011genome copies/eye) administered via subretinal delivery. Assessments of safety and efficacy are being conducted with the Primary Endpoints at week 26 and continued assessments to week 106. Measurements include: ocular and systemic adverse events, RGX-314 aqueous protein level, vision, central retinal thickness (CRT), and additionalanti-VEGF injectionsneeded post-RGX-314.
Twenty-four nAMD subjects (Cohort 1 to 4) have been enrolled into the dose-escalation trial. To date, RGX-314 has been well tolerated with no drug-related adverse events or drug-related serious adverse events. Dose dependent protein production was observed in cohorts 1-3. Cohort 3 showed sustain RGX-314 protein production from one month to six months with stability in vision and anatomy despite few to no injections. Cohort 3 (6 x 1010 GC/eye) had three subjects (50%) which have not needed any additional anti-VEGF injections in nine months with anatomic stability ( CRT -37 ?m) and improved vision (+13 ETDRS letters) from baseline through nine months. The first six subjects in Cohort 4 had a 1 month mean aqueous protein level higher than Cohort 3.
Subretinal administration of RGX-314 in 24 nAMD subjects has been tolerated and initial results show potential for the treatment of nAMD requiring continued therapy