Genentech: New 2-Year Data Confirm Vabysmo Improves Vision With Fewer Treatments for Wet AMD

Genentech announced new 2-year data from the TENAYA and LUCERNE studies that reinforce the long-term efficacy, safety and durability of Vabysmo (faricimab-svoa) in wet age-related macular degeneration (AMD). The 2-year data were presented at the 2022 American Society of Retina Specialists Annual Scientific Meeting on July 14.

“These longer-term results reinforce confidence in Vabysmo and support its continued use in people with wet AMD,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, said in a company news release. “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.”

In the TENAYA and LUCERNE studies, at 2 years:

• More than 60% of people receiving Vabysmo could be treated every 4 months—an increase of over 15 percentage points since the primary analysis at 1 year—while achieving comparable vision gains versus aflibercept given every 2 months.
• Nearly 80% of people receiving Vabysmo could be treated every 3 months or longer.
• Patients treated with Vabysmo received a median number of 10 injections over the 2 years versus 15 injections for those patients treated with aflibercept, potentially decreasing the number of injections.
• Comparable reductions in central subfield thickness (CST) were observed with Vabysmo given at intervals of up to 4 months versus aflibercept given every 2 months.
• No new safety signals were identified, and Vabysmo continued to be well tolerated, with a favorable benefit-risk profile.

The primary analyses at 1 year formed the basis of the recent wet AMD approvals in the US, Japan, the UK, and several other countries around the world. Vabysmo is also approved in these countries for diabetic macular edema (DME). Vabysmo is currently under review by the European Medicines Agency for these conditions, and submissions to other regulatory authorities around the world are ongoing.

Vabysmo is the first bispecific antibody for the eye and the only injectable eye medicine approved by the FDA with the option for treatments from 1 to 4 months apart in the first year following four initial monthly loading doses, based on evaluation of the patient’s anatomy and vision outcomes. Vabysmo 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 2-Year Results

In the TENAYA and LUCERNE studies, wet AMD patients received Vabysmo given at intervals of 2, 3 or 4 months or aflibercept given every 2 months. In the second year, the dosing schedule for Vabysmo patients could be adjusted based on their response to treatment.

At 2 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 Vabysmo 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 Vabysmo arm and +5.2 letters in the aflibercept arm.

Furthermore, 59% (n=160/271) of Vabysmo patients in TENAYA and 67% (n=192/287) in LUCERNE achieved 4-month dosing at 2 years. This is an increase over 1-year results, which showed 46% (n=144/315) of Vabysmo patients in TENAYA and 45% (n=142/316) in LUCERNE achieved 4-month dosing. An additional 15% (n=41/271) of Vabysmo patients in TENAYA and 14% (n=41/287) in LUCERNE achieved 3-month dosing at 2 years. Combined, more than 78% of Vabysmo patients were able to go 3 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 Vabysmo given at intervals of up to 4 months versus aflibercept given every 2 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 robust phase 3 clinical development program for Vabysmo. The program includes AVONELLE-X, an extension study of TENAYA and LUCERNE evaluating the long-term safety and tolerability of Vabysmo in wet AMD, and RHONE-X, an extension study of YOSEMITE and RHINE evaluating the long-term safety and tolerability of Vabysmo in DME. Additionally, the COMINO and BALATON trials are also underway, evaluating the efficacy and safety of Vabysmo in people with macular edema following retinal vein occlusion. Genentech has also initiated the phase 4 Elevatum study of Vabysmo in underrepresented patient populations with DME.

About the TENAYA and LUCERNE Studies

TENAYA (NCT03823287) and LUCERNE (NCT03823300) are two identical, randomized, multicenter, double-masked, global phase 3 studies evaluating the efficacy and safety of Vabysmo compared to aflibercept in 1,329 people living with wet AMD (671 in TENAYA and 658 in LUCERNE). The studies each have two treatment arms: Vabysmo 6 mg administered at intervals of 2, 3 or 4 months, following four 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 2-month intervals after three initial monthly doses. At week 60, patients randomized to the Vabysmo arm were treated using a treat-and-extend approach up to week 108. Dosing schedule for Vabysmo 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 BCVA score from baseline, averaged over weeks 40, 44, and 48. Secondary endpoints include safety; the percentage of participants in the Vabysmo arm receiving treatment every 2, 3 and 4 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.