ARVO 2023: New faricimab data suggest greater retinal drying versus aflibercept in wet AMD, DME

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Genentech announced post-hoc data indicate treatment with faricimab-svoa (Vabysmo) led to greater and faster drying of retinal fluid with fewer injections compared to aflibercept in wet, or neovascular, age-related macular degeneration (AMD).

In diabetic macular edema (DME), post-hoc data suggest faricimab-svoa treatment resulted in faster drying with fewer injections as well as less blood vessel leakage in the macula, the center of the retina, compared to aflibercept. The analyses from the Phase III TENAYA and LUCERNE (wet AMD) and YOSEMITE and RHINE (DME) studies were shared in three presentations at the 2023 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting held from April 23-27 in New Orleans.

Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, noted in a release reducing retinal fluid is associated with improved vision.

“These data continue to reinforce Vabysmo's ability to dry the retina and potential to make a meaningful difference for people with vision-threatening eye conditions,” Garraway said.

Faricimab-svoa is the first bispecific antibody for the eye and is currently approved in 60 countries to treat wet AMD and DME, with more than 800,000 faricimab-svoa doses distributed globally. Wet AMD and DME are two leading causes of vision loss, together affecting more than two million people in the United States and 40 million people globally. In these conditions, blood vessel leakage can cause a build-up of fluid and swelling in the back of the eye, contributing to sight loss.

“These findings suggest that Vabysmo may provide better stability of blood vessels in the macula,” said Roger Goldberg, MD, MBA, an ophthalmologist at Bay Area Retina Associates in Walnut Creek, Calif. and a Vabysmo Phase III study investigator. “Blood vessel stability may contribute to faster drying and extended durability.”

Data on retinal drying in wet AMD

A post-hoc analysis of pooled data from the head-to-head dosing period (weeks 0-12) of the Phase III TENAYA and LUCERNE studies in wet AMD showed:*

• Faricimab-svoa reduced retinal fluid from baseline compared to aflibercept, as measured by reduction in central subfield thickness (CST).
• At 12 weeks, CST reductions were 145 µm in the faricimab-svoa arm and
  133 µm in the aflibercept arm.
• A larger proportion of faricimab-svoa patients (77%) had absence of retinal fluid at 12 weeks versus aflibercept (67%), as measured by subretinal and intraretinal fluid (SRF and IRF).
• Absence of retinal fluid, as measured by absence of SRF and IRF observed in 75% of patients in each treatment arm, occurred at eight weeks with faricimab-svoa versus 12 weeks with aflibercept, corresponding to a fewer number of injections for faricimab-svoa patients versus aflibercept.

Data on retinal drying and blood vessel leakage in DME

A post-hoc analysis of pooled two-year data from the Phase III YOSEMITE and RHINE studies in DME compared time to fluid control between faricimab-svoa and aflibercept, as measured by absence of DME and absence of IRF.

The analysis showed:

• Absence of DME, defined as CST <325 µm observed in 75% of patients in each treatment arm, occurred at 20 weeks with faricimab-svoa versus 36 weeks with aflibercept – a difference of nearly four months.
• Absence of retinal fluid, as measured by absence of IRF observed in 50% of patients in each treatment arm, occurred more than eight months earlier in faricimab-svoa patients versus aflibercept.
• Absence of IRF occurred at 48 weeks with faricimab-svoa versus 84 weeks with aflibercept, corresponding to a fewer number of injections for faricimab-svoa patients versus aflibercept.

A separate post-hoc analysis of pooled data from the head-to-head dosing period (weeks 0-16) of the YOSEMITE and RHINE studies evaluated blood vessel leakage in the macula – an important marker of vascular stability. Blood vessel leakage in the macula may lead to more retinal fluid, which can cause swelling and blurry vision. Results showed:*

• The macular leakage area in faricimab-svoa patients was more than 50% smaller compared to aflibercept at 16 weeks.
• Faricimab-svoa reduced the macular leakage area to 3.6 mm2 from baseline compared to 7.6 mm2 with aflibercept.
• Nearly twice as many patients (28.4%) had resolution of leakage versus aflibercept (15.2%) at 16 weeks.

*P-values are nominal and not adjusted for multiplicity; no formal statistical conclusion should be made based on the P-values.

About the TENAYA and LUCERNE studies

According to the company, TENAYA (NCT03823287) and LUCERNE (NCT03823300) are two identical, randomized, multicenter, double-masked, global Phase III studies evaluating the efficacy and safety of faricimab-svoa 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: Faricimab-svoa 6 mg administered at intervals of two, three, or four 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 two-month intervals after three initial monthly doses.

At week 60, patients randomized to the faricimab-svoa arm were treated using a treat-and-extend approach up to week 108. The dosing schedule for faricimab-svoa patients during the treat-and-extend phase was adjusted based on treatment response as determined by 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 Vabysmo 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.

About the YOSEMITE and RHINE Studies

Moreover, the company noted YOSEMITE (NCT03622580) and RHINE (NCT03622593) are two identical, randomized, multicenter, double-masked, global Phase III studies evaluating the efficacy and safety of faricimab-svoa compared to aflibercept in 1,891 people with diabetic macular edema (940 in YOSEMITE and 951 in RHINE). The studies each have three treatment arms: faricimab-svoa 6.0 mg administered up to every four months after four initial monthly doses using a treat-and-extend approach; faricimab-svoa 6.0 mg administered at two-month intervals after six initial monthly doses; and aflibercept administered at fixed two-month intervals after five initial monthly doses. The dosing schedule for patients within the treat-and-extend arm was determined by CST and visual acuity. In all three 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 (the best distance vision a person can achieve – including with correction such as glasses – when reading letters on an eye chart) from baseline at one year, averaged over weeks 48, 52, and 56. Secondary endpoints include: safety; the percentage of participants in the treat-and-extend arm receiving faricimab-svoa every one, two, three, and four months, at week 52; the percentage of participants achieving a two-step or greater improvement from baseline in diabetic retinopathy severity at week 52; the percentage of participants achieving a gain, and the percentage avoiding a loss, of 15 letters or more in BCVA from baseline over time; change in CST from baseline over time; and percentage of patients with absence of intraretinal fluid over time.