Phase 3 Data Show Efficacy, Durability of Faricimab In Patients with nAMD, DME

New research recently published in The Lancet evaluated the efficacy, durability, and safety of intravitreal faricimab in patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).

Faricimab is a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody, with an expected FDA approval in January 2022.

Data was obtained from a series of landmark phase 3 studies, including the TENAYA and LUCERNE and YOSEMITE and RHINE. The former reported the primary results evaluating intravitreal faricimab with extension up to 16 weeks for neovascular age-related macular degeneration (nAMD), while the latter aimed to reduce treatment burden and optimize patient outcomes in diabetic macular edema (DME).

According to the data, faricimab helped patients with both indications improve and maintain their vision, with about half of patients able to extend the time between treatment up to 4 months, while generally well-tolerated.

TENAYA and LUCERNE

The TENAYA and LUCERNE studies reported phase 3 results evaluating intravitreal faricimab with extension up to every 16 weeks for nAMD.

Both TENAYA and LUCERNE were randomized, double-masked, non-inferiority trials across 271 worldwide sites. Included nAMD patients were treatment-naive and aged 50 years or older.

They were assigned 1:1 to intravitreal faricimab 6.0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2.0mg every 8 weeks.

Primary endpoints were considered the mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 in the intention-to-treat population. Additionally, the safety analyses included patients who received ≥1 one dose of study treatment.

Within the 2 trials, 1329 patients were randomly assigned between February - November 2019 in TENAYA (faricimab, n = 334 and aflibercept, n = 327) and between March - November 2019 in LUCERNE (faricimab, n = 331 and aflibercept, n = 327).

The BCVA change from baseline with faricimab was noninferior to aflibercept in TENAYA (adjusted mean change 5.8 letters, 95% CI, 4.6 - 7.1 and 5.1 letters; 95% CI, 3.9 - 6.4), at a treatment difference of 0.7 letters (95% CI, -1.1 to 2.5).

This was additionally observed in the LUCERNE trial (6.6 letters, 95% CI, 5.3 - 7.8 and 6.6 letters and 6.6 letters, 95% CI, 5.3 - 7.8), with no treatment difference observed (95% CI, -1.7 to 1.8).

Moreover, rates of ocular adverse events were comparable between faricimab and aflibercept in both TENAYA (n = 121, 36.3% versus n = 128, 38.1%) and LUCERNE (n = 133, 40.2% versus n = 118, 36.2%).

“Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD,” said study author Jeffrey S. Heier, MD, Ophthalmic Consultants of Boston.

The study, “Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials," was published in the Lancet.

YOSEMITE and RHINE

YOSEMITE and RHINE were randomized, double-masked, non-inferiority trials that took place across 353 sites worldwide.

Adults with vision loss due to center-involving DME were randomly assigned (1:1:1) to intravitreal faricimab 6.0 mg every 8 weeks, faricimab 6.0 mg per personalized treatment interval (PTI), or aflibercept 2.0 mg every 8 weeks up to week 100.

Investigators noted PTI dosing intervals were extended, maintained, or reduced every 4 weeks up to 16 weeks, which was based on disease activity at active dosing visits.

Primary endpoints were considered mean-change in BCVA at 1 year, average over weeks 48, 52, and 56. The efficacy analysis included in intention-to-treat population (non-inferiority margin 4 Early Treatment DIabetic Retinopathy Study (ETDRS) letters) while the safety analyses included patients with ≥1 dose of study treatment.

A total of 3247 patients were screened for eligibility in YOSEMITE (n = 1532) and RHINE (n = 1715). Following the exclusion period, 940 patients were enrolled into YOSEMITE between September 2018 - 2019 and 951 patients were enrolled into RHINE between October 2018 - September 2019.

The total patient population were randomly assigned to faricimab every 8 weeks (YOSEMITE, n = 315; RHINE, n = 317), faricimab PTI (n = 313, n = 319), or aflibercept every 8 weeks (n = 312, n = 315).

The noninferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean versus aflibercept every 8 weeks in YOSEMITE, 10.7 ETDRS letters, 97.52% CI, 9.4 - 12.0 versus 10.9 ETDRS letters, 97.52%, 9.6 - 12.2), at a difference of -0.2 ETDRS letters (-2.0 to 1.6).

It was additionally achieved in RHINE (11.8 ETDRS letters versus 10.3 ETDRS letters, difference of 1.5 ETDRS letters) and faricimab PTI (YOSEMITE 11.6 ETDRS letters, difference 0.7 ETDRS letters; RHINE 10.8 ETDRS letters, difference 0.5 ETDRS letters).

Further, the incidence of ocular adverse events was found to be comparable between faricimab every 8 weeks (YOSEMITE, n = 98, 31%, RHINE, n = 137, 43%; faricimab PTI, n = 106, 34%, n = 119, 37%, and aflibercept every 8 weeks, n = 102, 33%, n = 113, 36%).

“Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular edema,” wrote study author Charles C Wykoff, MD, Retina Consultants of America, Blanton Eye Institute.

The study, “Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials,” was published in The Lancet.