In the TENAYA and LUCERNE studies, more than 60% of faricimab patients could be treated every 4 months at 2 years, an increase from 45% at year 1. Study results are being presented at the American Society of Retina Specialists 2022 annual meeting in New York.
Genentech today announced new two-year data from the TENAYA and LUCERNE studies that reinforce the long-term efficacy, safety and durability of faricimab (Vabysmo) wet, or neovascular, age-related macular degeneration (AMD), a leading cause of vision loss.
According to the company, wet AMD affects nearly 1.1 million people in the U.S. and can require treatment with eye injections every one to two months. The two-year data were presented at the American Society of Retina Specialists 2022 annual scientific meeting being held in New York.
Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, pointed out that the longer-term results reinforce confidence in faricimab (Vabysmo) and support its continued use in people with wet AMD.
“With the potential to require fewer injections over time, Vabysmo continues to represent an important step forward for people with vision-threatening retinal conditions, and these data exemplify our commitment to redefining standards of care and reducing treatment burden," he said.
The company noted in a news release that in the TENAYA and LUCERNE studies, at two years:
The primary analyses at 1 year formed the basis of the recent wet AMD approvals in the U.S., Japan, the U.K. and several other countries around the world. Faricimab is also approved in these countries for diabetic macular edema (DME).
According to Genentech, faricimab is currently under review by the European Medicines Agency for these conditions, and submissions to other regulatory authorities around the world are ongoing.
Faricimab is the first bispecific antibody for the eye and the only injectable eye medicine approved by the FDA with the option for treatments from one to four months apart in the first year following four initial monthly loading doses, based on evaluation of the patient’s anatomy and vision outcomes.
The company noted in its news release that faricimab is designed to block two disease pathways linked to a number of vision-threatening retinal conditions by neutralizing angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A). While research is underway to better understand the role of the Ang-2 pathway in retinal disease, Ang-2 and VEGF-A are thought to contribute to vision loss by destabilizing blood vessels, which may cause new leaky blood vessels to form and increase inflammation.
Detailed Two-Year Results
According to the news release, in the TENAYA and LUCERNE studies, patients diagnosed with wet AMD patients received faricimab given at intervals of 2, 3 or 4 months or aflibercept given every two months. In the second year, the dosing schedule for faricimab patients could be adjusted based on their response to treatment.
Moreover, the company noted that at two years, vision improvements were comparable across both treatment arms. In TENAYA, the average vision gains from baseline at two years were +3.7 eye chart letters in the faricimab arm and +3.3 letters in the aflibercept arm. In LUCERNE, the average vision gains from baseline at two years were +5.0 letters in the faricimab arm and +5.2 letters in the aflibercept arm.
Furthermore, 59% (n=160/271) of faricimab patients in TENAYA and 67% (n=192/287) in LUCERNE achieved four-month dosing at two years. This is an increase over one-year results, which showed 46% (n=144/315) of faricimab patients in TENAYA and 45% (n=142/316) in LUCERNE achieved four-month dosing. An additional 15% (n=41/271) of faricimab patients in TENAYA and 14% (n=41/287) in LUCERNE achieved three-month dosing at two years. Combined, more than 78% of faricimab patients were able to go three months or longer between treatments at the end of the second year.
In both studies, comparable reductions in central subfield thickness (CST) were observed with faricimab given at intervals of up to four months versus aflibercept given every two months. Safety results were consistent across study arms, with no reported cases of retinal vasculitis or intraocular inflammation (IOI) associated with retinal vein or retinal artery occlusion.
Genentech has a Phase III clinical development program for faricimab. The program includes AVONELLE-X, an extension study of TENAYA and LUCERNE evaluating the long-term safety and tolerability of the therapeutic in wet AMD, and RHONE-X, an extension study of YOSEMITE and RHINE evaluating the long-term safety and tolerability of faricimab in DME.
Additionally, the COMINO and BALATON trials are also underway, evaluating the efficacy and safety of faricimab in people with macular edema following retinal vein occlusion. Genentech has also initiated the Phase IV Elevatum study of Vabysmo in underrepresented patient populations with DME.
About the TENAYA and LUCERNE Studies
According to the company, TENAYA (NCT03823287) and LUCERNE (NCT03823300) are two identical, randomly assigned, multicenter, double-masked, global Phase III studies evaluating the efficacy and safety of fricimab compared to aflibercept in 1,329 people living with wet AMD (671 in TENAYA and 658 in LUCERNE).
Moreover, Genentech noted that the studies each have two treatment arms: Faricimab 6 mg administered at intervals of 2, 3 or 4 months, following 4 initial monthly doses, selected based on objective assessment of disease activity as measured by optical coherence tomography and visual acuity evaluations at weeks 20 and 24; and aflibercept 2 mg administered at fixed two-month intervals after three initial monthly doses. At week 60, patients randomized to the faricimab arm were treated using a treat-and-extend approach up to week 108. Dosing schedule for faricimab patients during the treat-and-extend phase was adjusted based on treatment response as determined by central subfield thickness (CST) and visual acuity. In both arms, sham injections were administered at study visits when treatment injections were not scheduled to maintain the masking of investigators and participants.
The primary endpoint of the studies is the average change in best-corrected visual acuity (BCVA) score (the best distance vision a person can achieve – including with correction such as glasses – when reading letters on an eye chart) from baseline, averaged over weeks 40, 44 and 48. Secondary endpoints include safety; the percentage of participants in the faricimab arm receiving treatment every two, three and four months; the percentage of participants achieving a gain, and the percentage avoiding a loss, of 15 letters or more in BCVA from baseline over time; and change in CST from baseline over time.