Khanani AM, Patel SS, Ferrone PJ, Osborne A, Sahni J, Grzeschik S, Basu K, Ehrlich JS, Haskova Z, Dugel PU. Efficacy of Every Four Monthly and Quarterly Dosing of Faricimab vs Ranibizumab in Neovascular Age-Related Macular Degeneration (The STAIRWAY Phase 2 Randomized Clinical Trial). JAMA Ophthalmol. 2020;138(9):964-972.
Faricimab is a bispecific antibody that binds both VEGF-A and angiopoietin (ang) 2, and it is a promising investigative therapy for neovascular AMD. Ang2 competes with Ang1 for binding at tyrosine kinase with immunoglobulinlike domains 2 (Tie2) receptors on vascular endothelial cells. Normally, Ang1 binding to Tie2 maintains a healthy retinal vasculature; when Ang2 blocks Ang1 from binding to Tie2, leakage and neovascularization can result. Thus, preventing Ang2 from blocking Ang1 mediated stimulation of Tie2, in addition to blocking VEGF-A, could result in faricimab being a more effective, longer lasting treatment for neovascular AMD than current anti-VEGF therapies.
In the STAIRWAY phase 2 randomized clinical trial, investigators compared the mean change in best corrected visual acuity) at week 40 among 76 participants who were randomized to 1 of 3 groups: 1) ranbizumab 0.5 mg dosed monthly; 2) faricimab 6.0 mg dosed q 12 weeks; or 3) faricimab 6.0 mg dosed q 16 weeks. Participants in the faricimab arms received 4 loading doses of faricimab (1 injection per month x 4 months) before being extended to 12 or 16 weeks. The main finding was that visual acuity gains were comparable in all 3 groups (+11.4, +9.3, and +12.5 letters in the ranibizumab, faricimab q12w, and faricimab q16w groups, respectively). Ranibizumab patients received approximately twice as many injections as the faricimab groups over the course of 1 year (though “rescue” treatments for persistent or recurrent disease activity were not allowed in the faricimab groups). However, a much higher percentage of ranibizumab patients (94%, 15/16) had no disease activity at the week 24 assessment compared to the faricimab treated patients (65%, 36/55) at the same time point.
Ultimately physicians and patients care about preserving vision, and the results of this study are promising in that visual acuity gains were comparable among all 3 groups of patients, with the faricimab treated groups receiving roughly half the number of injections as the ranibizumab group over the course of 1 year. Disturbing though is the high rate (35%) of “disease activity” at week 24 in the faricimab treated groups (12 weeks after the last loading injection) compared to the 6% rate of disease activity in the ranibizumab group (4 weeks after their most recent injection). Interpretation of this data is difficult since the treatment frequencies were different between the faricimab and ranibizumab groups. It would have been interesting to compare the disease activity rate between ranibizumab and faricimab after an equivalent dosing schedule, such as treat and extend in both groups. However, the authors chose not to employ a treat and extend strategy for the ranibizumab group since it is not an accepted dosing regimen per the Food and Drug Administration. Nevertheless, since most retinal specialists use a treat-and-extend approach to neovascular AMD management, it will be important to determine if faricimab injections, when used in a treat and extend paradigm, are actually able to offer increased durability and comparable visual acuity gains relative to existing anti-VEGF agents.
Maxwell S. Stem, MD
Pennsylvania Retina Specialists, PC