Genentech announced positive results from the phase 2 STAIRWAY study which explored the extended durability of faricimab (RG7716) in the treatment of wet age-related macular degeneration (AMD). At 52 weeks, faricimab patients dosed either every 16 weeks or every 12 weeks demonstrated sustained vision outcomes comparable to ranibizumab dosed every 4 weeks. Results of the study were presented as a late-breaking oral presentation during the 2018 American Academy of Ophthalmology’s (AAO) 122nd Annual Meeting in Chicago, Illinois.
“Because current anti-VEGF monotherapies for wet AMD are burdensome, requiring frequent clinic visits for eye injections, some people are under-treated and experience subsequent declining vision over time,” Sandra Horning, MD, chief medical officer and head of Global Product Development, said in a company news release. “The STAIRWAY data show the potential of faricimab to allow fewer injections while achieving and sustaining the same visual gains seen with a current standard of care. Based on these data, we will be initiating a global phase 3 program for faricimab in wet AMD.”
STAIRWAY is a 52-week study that assessed two extended dosing regimens of faricimab 6.0 mg given every 16 weeks or every 12 weeks, compared to ranibizumab 0.5 mg every 4 weeks. At week 24 (3 months after the last of four loading doses), patients randomized to faricimab every 16 weeks were switched to 12-week dosing if they were shown to have active disease, per pre-defined criteria. At week 24, 65 percent (n=36/55) of people treated with faricimab had no active disease, highlighting the potential of 16-week dosing in nearly two-thirds of patients. Initial vision gains, as measured by Best Corrected Visual Acuity (BCVA), were fully maintained through to week 52 with 16- and 12-week dosing regimens. People treated with faricimab dosed every 16 weeks experienced a mean improvement of 11.4 chart letters from baseline, compared to 10.1 letters in patients treated with faricimab dosed every 12 weeks and 9.6 letters in patients treated with ranibizumab 0.5 mg dosed every 4 weeks. The three treatment regimens were similar in both the proportion of patients gaining more than 15 letters and avoiding a loss of more than 15 letters. Comparable reductions in central retina thickness were also observed in people treated with both dosing intervals of faricimab and those treated with ranibizumab. In STAIRWAY, the rates of ocular and systemic adverse events observed with faricimab were similar to the rates observed with ranibizumab. No new safety signals were observed. The overall safety profile of faricimab appears consistent with the safety profile reported in patients with wet AMD who receive intravitreal anti-VEGF therapies.
In addition, data on the investigational Port Delivery System with ranibizumab (PDS) in patients with wet AMD were also presented at the AAO Annual Meeting, comprising further data from the phase 2 Ladder study, and the trial design of the phase 3 Archway study. The small, refillable eye implant, which is slightly longer than a grain of rice, is designed to allow most people with wet AMD to go 6 months without needing a refill.
Topline results presented earlier this year showed the majority of PDS patients – including approximately 80 percent of patients in the high-dose PDS group – went 6 months or longer between the implantation and the first required refill of the device. Importantly, patients in the high-dose PDS group achieved similar visual outcomes as ranibizumab 0.5 mg dosed every four weeks. Based on the data of the phase 2 Ladder program, the pivotal phase 3 Archway clinical trial and the Portal label extension study were initiated in September 2018. These studies will evaluate the efficacy and safety of the PDS 100 mg/mL concentration in patients with wet AMD at a fixed dosing interval of 24 weeks.
Faricimab and the PDS are the two most advanced investigational treatments in Genentech and Roche’s robust ophthalmology pipeline. In addition to Archway, two pivotal phase 3 studies for faricimab are currently open and enrolling: RHINE (NCT03622593) and YOSEMITE (NCT03622580). These two studies are designed to investigate the efficacy and safety of faricimab compared with aflibercept in people with diabetic macular edema (DME). Based on STAIRWAY, a global phase 3 program for faricimab in wet AMD is anticipated to commence in 2019.