May 31, 2019 Conference


Gene Therapy for Neovascular Age Related Macular Degeneration

Dr. Allen Ho, Wills Eye Hospital (Presenter)

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