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Carl Danzig, MD, presented results of phase 2 Stairway Trial during the virtual 2020 American Society of Retina Specialists (ASRS) annual meeting.
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Faricimab (Roche), when tested at extended dosing intervals of every 16 weeks and every 12 weeks, provided sustained anatomic and visual outcomes comparable to those achieved with ranibizumab (Lucentis, Genentech Inc.) dosed every 4 weeks.
The phase 2 Stairway Trial showed that the drug blocked angiopoietin 2 (Ang-2) and vascular endothelial growth factor (VEGF), both of which synergistically drive vascular instability, characterized by vascular leakage, neovascularization, and inflammation in retinal diseases such as age-related macular degeneration (AMD), according to Carl Danzig, MD, who presented results of the trial during the virtual 2020 American Society of Retina Specialists annual meeting.
Faricimab is the first bispecific antibody designed for intraocular use and can simultaneously bind and neutralize Ang-2 and VEGF-A.
He explained that the bispecific antibody has 2 Fab arms in a specifically engineered Fc region: Anti-Ang-2 Fab stabilizes and protects vessels and anti-VEGF-A Fab inhibits vascular leakage and neovascularization.
The phase 2 multicenter, randomized, controlled clinical study evaluated the extended durability of faricimab for treating neovascular AMD.
Specifically, the investigators assessed the effects of every-16-week flex doses or every-12-week doses of faricimab compared with monthly ranibizumab. All patients treated with faricimab first received 4 doses administered every 4 weeks through week 12 (loading dose) followed by a 12-week period with no treatment.
At week 24, the disease activity was assessed, including measurement of the central subfield thickness and BCVA, presence of macular hemorrhages, and the investigators’ opinions.
The primary efficacy objective was the change in the best-corrected visual acuity (BCVA) from baseline.
The patients randomized to the every-16-week flex dosing who had active disease at 24 weeks went on to every-12-week dosing. Those without active disease were eligible for every-16-week dosing.
“Overall, 65%, that is, 36 of 55 patients treated with faricimab were free of disease activity at week 24; 19 of 31 patients in the every-16-week flex group had no disease activity at week 24 and were treated at every-16-week intervals to week 52,” Danzig said. “All other patients were treated with every-12-week dosing.”
Measurements of the BCVA showed that the gains in vision achieved with the every-16-week flex dosing and every-12-week dosing were maintained at week 52 and were comparable to those seen with monthly ranibizumab (+11.42, +10.08, and +9.59 letters, respectively).
Improvements in BCVA, central subfield thickness, choroidal neovascularization lesion size, and area of leakage with faricimab dosed every-16-week flex and every 12 weeks were comparable to those achieved with monthly ranibizumab.
According to Danzig, the main take-home points of the study include Ang-2 and VEGF-A are key drivers of vascular instability characterized by vascular leakage, neovascularization, and inflammation. Faricimab is the first bispecific antibody designed to simultaneously inhibit Ang-2 and VEGF-A.
The Stairway trial showed that the initial BCVA gains were meaningful and fully maintained through week 52 with every-16-week flex and every-12-week dosing arms.
No active disease was seen in 65% of all patients treated with faricimab 12 weeks after the last loading dose and were eligible for every-16-week dosing. Anatomic improvements were comparable between faricimab and ranibizumab.
According to Danzig, based on the Stairway trial results, 2 large phase 3 studies, Tenaya and Lucerne, are assessing the efficacy, safety, and durability of faricimab in patients with neovascular AMD. The drug is also under investigation in phase 3 clinical trials to treat diabetic macular edema.
Carl Danzig, MD
Dr Danzig is a consultant to Genentech Inc. He is is in private practice at the Rand Eye Institute, Pompano Beach, Florida.