Brolucizumab monotherapy may lead to “robust” gains in best corrected visual acuity (BCVA) comparable with aflibercept treated eyes with polypoidal choroidal vasculopathy (PCV), according to research results published in the British Journal of Ophthalmology.
HAWK (ClinicalTrials.gov identifier NCT02307682) is a prospective, 2-year, randomized, double-masked, multicenter, phase 3 clinical trial conducted in 10 countries between 2014 and 2018. Researchers conducted a subanalysis of HAWK study data and compared the safety and efficacy of 2 agents — brolucizumab and aflibercept — in eyes with PCV spanning a 96-week study period.
Included participants were adults 50 years or older with intraretinal or subretinal fluid, or both, that affected the central subfield, a best corrected visual acuity (BCVA) between 78 and 23 ETDRS letters, and no fibrosis or geographic atrophy in the central subfield. Participants were randomly assigned 1:1:1 to receive either brolucizumab 3 mg (n=358) or 6 mg (n=360) or aflibercept 2 mg (n=360).
In the brolucizumab groups, 3 monthly loading doses were given at weeks 0, 4, and 8; intravitreal injections were given every 12 weeks thereafter, adjusted to every 8 weeks thereafter if disease activity was detected. In the aflibercept group, medication was received every 8 weeks. Disease activity assessments were performed at weeks 16 through 20, and at weeks 32, 44, 56, 68, 80, and 92.
The total cohort for the subanalysis included 152 Japanese patients enrolled in HAWK. Of these, 59% were diagnosed with PCV at screening: 20 in the brolucizumab 3 mg group, 39 in the 6 mg group, and 30 in the aflibercept group.
Baseline characteristics were well-balanced among the participants in this subanalysis, excepting central subfield thickness which was 50 µm lower in the brolucizumab 6 mg group. Mean baseline BCVA in patients with PCV was 62.4 ETDRS in both treatment arms.
Investigators observed “robust” gains in BCVA in patients with BCVA in the treatment arms. At week 48, mean BCVA change in baseline was +10.4 and +11.6 letters in the brolucizumab 6 mg and aflibercept 2 mg groups, respectively. These gains were maintained through week 96 with mean changes from baseline of +11.4 and +11.1 letters.
These BCVA gains were achieved with the majority of those in the brolucizumab group on the every 12 week dosing schedule. For these eyes with PCV, the probability of maintaining exclusively an every 12 week dosing interval through weeks 48 and 96 was 76% and 68%.
At week 4, intraretinal and/or subretinal fluid was seen in fewer eyes treated with brolucizumab 6 mg vs aflibercept (48.7% vs 70%). This difference was observed early in the matched phase of the study at week 16 (35% vs 43.3%) and throughout the maintenance period to week 96 (12.8% vs 16.7%).
Absolute mean central subfield thickness at week 16 was 250 µm and 266 µm in the brolucizumab 6 mg and aflibercept 2 mg groups, respectively (baseline values, 393 µm and 445 µm). Mean central subfield thickness reduction from baseline to week 16 was 143±15 µm and 179±21 µm in each group, respectively. At week 48, these values were 149±17 µm and 182±21 µm, which were maintained through week 96.
Among patients with PCV, the brolucizumab safety profile was similar to that of the overall HAWK population. The most common ocular adverse events in each study arm were cataract and allergic conjunctivitis. Severe ocular adverse events included cataract and macular hole in the brolucizumab and aflibercept groups, respectively. A higher incidence of IOI events was reported in the brolucizumab group (15.4%) vs the aflibercept group.
Study limitations include the exploratory nature of the analysis, the small number of eyes in each treatment arm, and a lack of stratification by PCV status.
“Robust BCVA gains greater fluid resolution over 96 weeks were observed in eyes treated with brolucizumab…monotherapy compared with those treated with fixed [every 8 week] aflibercept dosing,” according to the research team. “These visual and anatomic outcomes were achieved through week 48.”
“There will be a growing need to manage eyes with PCV in many parts of the world, particularly in Asia where prevalence is high, as the population becomes increasingly aged,” the study says. “The results from this analysis suggest that brolucizumab could help to alleviate the treatment burden associated with PCV.”
Disclosure: This clinical trial was supported by Novartis Pharma AG. Multiple study authors declared affiliations with the biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Ogura Y, Jaffe GJ, Cheung CMG, et al. Efficacy and safety of brolucizumab versus aflibercept in eyes with polypoidal choroidal vasculopathy in Japanese participants of HAWK. Br J Ophthalmol. Published online July 22, 2021. doi:10.1136/bjophthalmol-2021-319090