Abstract
Purpose
To evaluate the efficacy, durability and safety of intravitreal faricimab versus aflibercept over 48 weeks in patients with neovascular age-related macular degeneration (nAMD) from the LUCERNE China subpopulation.
Design
LUCERNE (NCT03823300) was a phase 3 global, double-masked, active comparator-controlled trial. The China subpopulation comprised patients from mainland China, Taiwan and Hong Kong.
Methods
Treatment-naïve patients aged ≥50 years with nAMD were randomized 1:1 to receive faricimab 6.0 mg up to every 16 weeks (Q16W) based on prespecified disease criteria after four initial Q4W doses or aflibercept 2.0 mg Q8W after three initial Q4W doses. The primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA) averaged over weeks 40 to 48. Anatomical, durability and safety outcomes were also evaluated.
Results
The China subpopulation comprised 119 patients (faricimab: n = 59, aflibercept: n = 60). At weeks 40 to 48, adjusted mean (95% confidence interval [CI]) BCVA letter gains from baseline were +9.7 (7.4 to 12.0) and +9.8 (7.5 to 12.1) with faricimab and aflibercept, respectively. Central subfield thickness was reduced from baseline by weeks 40 to 48 in both arms, with an adjusted mean (95% CI) change of −145.4 µm (−156.2 to −134.6) and −156.5 µm (−167.3 to −145.7) for faricimab and aflibercept, respectively. By week 48, 87.3% of the patients were on extended ≥Q12W faricimab dosing. Faricimab was well tolerated with no new safety signals.
Conclusions
Faricimab up to Q16W showed durable efficacy in the LUCERNE China subpopulation, consistent with global findings. Faricimab may reduce treatment burden for patients with nAMD in China, without compromising efficacy.
1
Introduction
Age-related macular degeneration (AMD) is a leading cause of vision loss among the elderly population. In China, the prevalence of late-stage AMD ranged from 0.38% in people 45 to 49 years of age to 3.88% in people 85 to 89 years of age. Although the prevalence of AMD is lower for Asian subpopulations compared to global estimates, the prevalence of AMD in China is projected to rise significantly and may affect more than 55 million people by 2050.
Neovascular AMD (nAMD), a form of late-stage AMD, is a leading cause of severe visual impairment worldwide. The standard of care for nAMD is the use of anti–vascular endothelial growth factor (anti-VEGF) therapies to treat choroidal neovascularization (CNV). However, anti-VEGF therapies are not always effective for patients with nAMD. In addition, anti-VEGF treatment often demands regular healthcare visits for frequent intravitreal injections, contributing to a considerable burden and barriers to treatment. Thus, there is an unmet need for durable treatments for nAMD that can protect patients’ vision with fewer healthcare visits.
Faricimab is the first bispecific antibody designed for intraocular use, and it simultaneously and independently binds to both angiopoietin-2 (Ang-2) and VEGF-A with high affinity and specificity. In January 2022, faricimab was approved in the United States for the treatment of nAMD and diabetic macular edema and has since been approved for use in more than 90 countries as of December 2023. In the phase 3 global TENAYA and LUCERNE studies, faricimab was efficacious, durable and well tolerated in patients with nAMD in global population, Asia subpopulation (Hong Kong, Japan, Singapore, South Korea and Taiwan) and Japan subpopulation analyses.
The phase 3 TENAYA and LUCERNE studies (NCT03823287/NCT03823300) were designed to investigate the efficacy, safety and durability of intravitreal faricimab in treatment-naïve patients with nAMD across 112 weeks. The 48-week outcomes of the global TENAYA and LUCERNE studies have been previously published. To support the approval of faricimab in China for the treatment of patients with nAMD, the LUCERNE study included a China subpopulation. This comprised patients enrolled during the LUCERNE global enrollment phase (from mainland China, Taiwan and Hong Kong), as well as additional patients from mainland China recruited following the global enrollment phase (hereafter referred to as the China extension phase). The aim of the current analysis was to describe the 48-week efficacy, durability and safety of faricimab in the China subpopulation of the LUCERNE study.
2
Methods
2.1
Study design
LUCERNE (ClinicalTrials.gov identifier, NCT03823300) was a phase 3 global, multicenter, randomized, double-masked, active comparator-controlled, 112-week trial of faricimab in treatment-naïve patients with nAMD (N = 658). Patients with nAMD were randomized 1:1 to the following treatment arms: 1) faricimab up to every 16 weeks (Q16W): faricimab 6.0 mg was administered Q8W, Q12W or Q16W by intravitreal injection after four initial Q4W doses (dosing intervals were based on protocol-defined anatomical and best-corrected visual acuity [BCVA] measurements at weeks 20 or 24); and 2) aflibercept Q8W: aflibercept 2.0 mg (active comparator) was administered Q8W by intravitreal injection after three initial Q4W doses. Additional details on the LUCERNE study design, methods, statistics and the 48-week global findings have been previously published.
LUCERNE was conducted in accordance with the International Council for Harmonization’s E6 Guideline for Good Clinical Practice, tenets of the Declaration of Helsinki, U.S. Food and Drug Administration regulations, the European Union Clinical Trials Directive (2001/20/EC) and all applicable local, state and federal laws. Study protocols were approved by applicable institutional review boards and ethics committees before trial commencement, and all patients provided informed consent. The full list of investigators for the LUCERNE China subpopulation is provided in Supplementary Table 1 .
2.2
Study population
Analysis of the LUCERNE China subpopulation was performed. Patients were enrolled at 20 sites between March 2019 and July 2021. Patients from mainland China, Taiwan and Hong Kong were enrolled in the global enrollment phase. In addition, the China extension phase to support registration in China enrolled additional patients from mainland China. Patients were included in the study if they were ≥50 years of age and had treatment-naïve CNV secondary to AMD in the study eye. Additional inclusion criteria for the study eye included: 1) subfoveal CNV or juxtafoveal/extrafoveal CNV with a subfoveal component related to the CNV activity identified by either fundus fluorescein angiography (FFA) or optical coherence tomography (OCT); 2) a CNV lesion of any type, with a total lesion size of ≤9 disc areas on FFA, including blood, atrophy, fibrosis and neovascularization; 3) a CNV area of ≥50% of the lesion size; 4) evidence of leakage (active CNV confirmed on FFA) and presence of fluid (CNV exudation confirmed on OCT); and 5) BCVA of 78 to 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/32 to 20/320 approximate Snellen equivalent). Patients were excluded if the study eye had: 1) CNV or a history of macular pathology unrelated to AMD; 2) a retinal pigment epithelium (RPE) tear in the macula or vitreous hemorrhage on day 1; 3) subretinal hemorrhage, fibrosis or atrophy of the fovea or > 50 % of the total lesion area; 4) any concurrent intraocular condition that could reduce the potential for visual improvement or require intervention; 5) any prior treatment for CNV (including intravitreal anti-VEGF therapy); 6) any prior intravitreal treatment for any retinal disease; and 7) any prior intraocular surgery. Patients with polypoidal choroidal vasculopathy (PCV) were not excluded from the study.
2.3
Outcome measures
The following efficacy outcomes were reported for the intention-to-treat population: 1) change from baseline in BCVA (as measured on the ETDRS chart at a starting distance of 4 m), averaged over weeks 40, 44 and 48; 2) the proportion of patients gaining ≥15 BCVA letters and avoiding a loss of ≥15 BCVA letters from baseline, averaged over weeks 40, 44 and 48; 3) change from baseline in central subfield thickness (CST) (measured as the distance from the inner limiting membrane to the RPE), averaged over weeks 40, 44 and 48; and 4) the proportion of patients in the faricimab arm on a Q8W, Q12W or Q16W treatment interval at week 48. The incidence and severity of ocular and nonocular adverse events (AEs) are presented for the safety-evaluable population (all patients randomized in the study who received ≥1 injection of faricimab or aflibercept in the study eye).
2.4
Statistical analysis
The statistical methods used in this LUCERNE China subpopulation analysis were generally consistent with those described for the primary TENAYA and LUCERNE analyses. Continuous outcomes were analyzed using a mixed model for repeated measures. Binary endpoints were analyzed using unstratified estimation for binomial proportions. The estimates and confidence intervals (CIs) were provided for the mean (for continuous variables) or proportion (for binary variables) for each treatment arm and for the difference in means or proportions between the active comparator (aflibercept Q8W) and the faricimab arm. No formal statistical analysis was performed.
3
Results
3.1
Patients
A total of 119 patients in the LUCERNE China subpopulation were randomized into the study (n = 59 faricimab up to Q16W, n = 60 aflibercept Q8W; Supplementary Fig. 1 ) from both the global enrollment phase (28 out of 119, 23.5%) and the China extension phase (91 out of 119, 76.5%). Seven patients (5.9%) withdrew from the study before week 48: three patients in the faricimab arm (n = two patient decision; n = one physician decision) and four patients in the aflibercept arm (n = three patient decision; n = one AE). Baseline patient and ocular characteristics were similar between treatment arms in the LUCERNE China subpopulation ( Table 1 ).
| Characteristic | Faricimab up to Q16W (n = 59 a ) | Aflibercept Q8W (n = 60 a ) |
|---|---|---|
| Age, years, mean (SD) | 68.9 (8.1) | 69.5 (6.9) |
| Female, n (%) | 19 (32.2) | 21 (35.0) |
| BCVA, ETDRS letters, mean (SD) | 57.8 (13.7) | 57.2 (14.2) |
| CST, µm, mean (SD) | 356.4 (127.2) | 333.0 (131.6) |
| Phakic, n (%) | 51 (86.4) | 53 (88.3) |
| Absence of IRF, n (%) | 41 (69.5) | 33 (55.0) |
| Absence of SRF, n (%) | 17 (28.8) | 12 (20.0) |
| CNV location by FFA, n (%) | ||
| Subfoveal | 39 (66.1) | 38 (63.3) |
| Juxtafoveal | 16 (27.1) | 14 (23.3) |
| Extrafoveal | 4 (6.8) | 8 (13.3) |
| PCV by ICGA b , n (%) | 3 (21.4) c | 4 (36.4) c |
b Patient participation in ICGA (to assess PCV status) was optional and was conducted at 9 out of 20 study sites.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
