In the Journals

Wet AMD gene therapy well tolerated through 3 years

Patients with wet age-related macular degeneration who responded well to rAAV.sFLT-1 subretinal gene therapy at 1 year maintained that response through 3 years, but the existence of a biologic efficacy signal was unable to be confirmed.

Researchers assessed the safety and 3-year results of rAAV.sFLT-1 gene therapy in combined phase 1 and 2a randomized controlled trials for wet AMD. The trials included 13 patients in a control group and 24 patients in a gene therapy group. All patients received intravitreal ranibizumab 0.5 mg in the study eye at baseline and at a 4-week visit. Patients in the gene therapy group received a subretinal injection of 100 µL rAAV.sFLT-1 at the time of vitrectomy at day 7.

Anti-VEGF rescue treatment was provided when patients experienced a loss of 10 or more ETDRS letters from a previous visit or a loss of five or more ETDRS letters in conjunction with patient perception of functional loss. Rescue treatments were also provided with an increase in subsensory, intraretinal or subretinal pigment epithelial fluid on OCT or signs of increased leakage on fluorescein angiography.

At 12 months, the gene therapy patients were divided into two groups: 14 patients in group HD-1 required two or fewer anti-VEGF re-treatments in the first year and 10 patients in group HD-2 required more than two re-treatments.

Three adverse events and 33 serious adverse events were recorded between 1 year and 3 years, 15 in the control group and 21 in the gene therapy group. One control patient had transient choroiditis, and the other serious events were not related to the study.

Over the 3 years, control group patients received a median of seven re-treatments and lost a median of seven ETDRS letters, HD-1 patients received a median of 2.5 re-treatments and lost a median of four ETDRS letters, and HD-2 patients received a median of 11 re-treatments and lost a median of seven ETDRS letters. Four HD-1 patients maintained an improvement of 12 to 22 ETDRS letters from baseline at the 36-month visit. However, because these trials were designed for safety, meaningful analysis of efficacy was limited.

“Although these trials were unable to unequivocally confirm the existence of a biologic efficacy signal, they confirmed that rAAV.sFLT-1 gene delivery was well tolerated among the elderly,” the researchers wrote. – by Robert Linnehan

Disclosures: Rakoczy reports she has a patent licensed to Avalanche Biotechnologies. Please see the study for all other authors’ relevant financial disclosures.

Patients with wet age-related macular degeneration who responded well to rAAV.sFLT-1 subretinal gene therapy at 1 year maintained that response through 3 years, but the existence of a biologic efficacy signal was unable to be confirmed.

Researchers assessed the safety and 3-year results of rAAV.sFLT-1 gene therapy in combined phase 1 and 2a randomized controlled trials for wet AMD. The trials included 13 patients in a control group and 24 patients in a gene therapy group. All patients received intravitreal ranibizumab 0.5 mg in the study eye at baseline and at a 4-week visit. Patients in the gene therapy group received a subretinal injection of 100 µL rAAV.sFLT-1 at the time of vitrectomy at day 7.

Anti-VEGF rescue treatment was provided when patients experienced a loss of 10 or more ETDRS letters from a previous visit or a loss of five or more ETDRS letters in conjunction with patient perception of functional loss. Rescue treatments were also provided with an increase in subsensory, intraretinal or subretinal pigment epithelial fluid on OCT or signs of increased leakage on fluorescein angiography.

At 12 months, the gene therapy patients were divided into two groups: 14 patients in group HD-1 required two or fewer anti-VEGF re-treatments in the first year and 10 patients in group HD-2 required more than two re-treatments.

Three adverse events and 33 serious adverse events were recorded between 1 year and 3 years, 15 in the control group and 21 in the gene therapy group. One control patient had transient choroiditis, and the other serious events were not related to the study.

Over the 3 years, control group patients received a median of seven re-treatments and lost a median of seven ETDRS letters, HD-1 patients received a median of 2.5 re-treatments and lost a median of four ETDRS letters, and HD-2 patients received a median of 11 re-treatments and lost a median of seven ETDRS letters. Four HD-1 patients maintained an improvement of 12 to 22 ETDRS letters from baseline at the 36-month visit. However, because these trials were designed for safety, meaningful analysis of efficacy was limited.

“Although these trials were unable to unequivocally confirm the existence of a biologic efficacy signal, they confirmed that rAAV.sFLT-1 gene delivery was well tolerated among the elderly,” the researchers wrote. – by Robert Linnehan

Disclosures: Rakoczy reports she has a patent licensed to Avalanche Biotechnologies. Please see the study for all other authors’ relevant financial disclosures.