The latest results from a phase 3 trial suggest that the novel anti-VEGF agent brolucizumab, a single-chain antibody fragment, has promising durability and a similar efficacy to aflibercept for treating neovascular AMD, said Pravin Dugel, MD, during Friday’s Retina Subspecialty Day.
“Brolucizumab is the smallest known active unit of a human monoclonal antibody that allows for concentrated molar dosing,” said Dr. Dugel. With a molecular weight of only 26 kDa (compared with 48 kDa for ranibizumab and 115 kDa for aflibercept), a 6-mg dose can be delivered in a single 50-μL intravitreal injection.
A tale of 2 trials. HAWK and HARRIER trials are multicenter, randomized, double-masked trials of brolucizumab (6 mg) vs. aflibercept (3 mg). The 2 trials comprised more than 1,800 wet AMD patients. All patients received 3 monthly loading doses of the assigned treatment, followed by 12-week dosing intervals for brolucizumab eyes, with an option to adjust to an 8-week dosing based on disease activity. Aflibercept was administered every 8 weeks after the loading phase.
Outcomes show extended dosing is viable. At 48 weeks, brolucizumab achieved robust and consistent visual gains, and more than half of the study eyes were maintained on a 12-week dosing interval. Other outcomes that favored brolucizumab included:
- Significantly less disease activity at week 16
- Superior central subfield thickness improvement at weeks 16 and 48
- Significantly fewer patients with presence of intraretinal and/or subretinal fluid
- Overall safety comparable to aflibercept
Both the HAWK and HARRIER trials will continue to follow patients through 96 weeks, according to Dr. Dugel. The trials are expected to conclude in May 2018.—Keng Jin Lee
Correction: This article was updated on Nov. 11, 2017. The initial version incorrectly identified the research as being in phase 2.
Financial disclosures. : Acucela: C; Aerpio: C,O; Alcon Laboratories, Inc.: C; Alimera Sciences, Inc.: C,O; Allegro Ophthalmics, LLC: C,O; Allergan: C; Annidis: C,O; ArcticDx, Inc.: C; Bausch+Lomb: C; Boehringer Ingelheim Pharma GmbH: C; Byeonics: C; Chengdu Kanghong Biotechnology: C; Clearside Biomedical: C,O; DigiSight: C,O; DOSE Medical: C; Genentech: C; Graybug Vision: C; Irenix: C,O; Lux BioScience: C; Macusight: C; NeoVista, Inc.: C; Novartis, Alcon Pharmaceuticals: C; Omeros: C; Ophthotech: C,O; Opthea: C; Optos, Inc.: C; Optovue: C; ORA: C; PanOptica: C,O; Pentavision: C; Regeneron Pharmaceuticals, Inc.: C; Roche Diagnostics: C; Santen, Inc.: C; SciFluor Life Sciences: C; Shire Human Genetics: C; Stealth Biotherapeutics: C; ThromboGenics, Inc.: C; Topcon Medical Systems Inc.: C; TrueVision: C.
Disclosure key. C = Consultant/Advisor; E = Employee; L = Speakers bureau; O = Equity owner; P = Patents/Royalty; S = Grant support.