Ramin Tadayoni1, Laura Sararols2, Georges Weissgerber3, Rohini Verma3, Andreas Clemens4,5, Frank G Holz6. 1. Université de Paris, Ophthalmology Department, AP-HP, Hôpital Lariboisière, Paris, France. 2. Hospital General de Catalunya, Barcelona, Spain. 3. Novartis Pharma AG, Basel, Switzerland. 4. Novartis Pharma AG, Basel, Switzerland, andreas.clemens@novartis.com. 5. Department of Cardiology and Angiology I, Heart Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany, andreas.clemens@novartis.com. 6. Department of Ophthalmology, University of Bonn, Bonn, Germany.
Abstract
BACKGROUND: Despite the success of anti-vascular endothelial growth factors (anti-VEGFs), currently, there is a need for highly effective compounds that can alleviate the burden of managing neovascular age-related macular degeneration (nAMD). PURPOSE: To review the milestones in the molecular and clinical development of brolucizumab, the first single-chain antibody fragment (scFv) designed specifically for intraocular use in humans. METHODS: In this article, we summarize the preclinical and current clinical evidence of brolucizumab administration with an overview of the other treatment regimens and additional indications under investigation. RESULTS: The unique molecular design of brolucizumab led to a low molecular weight of only 26 kDa, allowing for a concentrated molar dose of 1 intravitreal injection compared with other anti-VEGF agents. Phase I and II clinical trial outcomes validated the efficacy of brolucizumab in the treatment of nAMD with signals of a more durable treatment effect. The pivotal phase III trials, HAWK and HARRIER, which included a total of 1,817 patients, established that brolucizumab can be administered every 3 months while maintaining disease control. CONCLUSIONS: The preclinical and clinical data on brolucizumab provide evidence of sustained disease control with longer injection intervals, thus potentially reducing the treatment burden in patients with nAMD.
BACKGROUND: Despite the success of anti-vascular endothelial growth factors (anti-VEGFs), currently, there is a need for highly effective compounds that can alleviate the burden of managing neovascular age-related macular degeneration (nAMD). PURPOSE: To review the milestones in the molecular and clinical development of brolucizumab, the first single-chain antibody fragment (scFv) designed specifically for intraocular use in humans. METHODS: In this article, we summarize the preclinical and current clinical evidence of brolucizumab administration with an overview of the other treatment regimens and additional indications under investigation. RESULTS: The unique molecular design of brolucizumab led to a low molecular weight of only 26 kDa, allowing for a concentrated molar dose of 1 intravitreal injection compared with other anti-VEGF agents. Phase I and II clinical trial outcomes validated the efficacy of brolucizumab in the treatment of nAMD with signals of a more durable treatment effect. The pivotal phase III trials, HAWK and HARRIER, which included a total of 1,817 patients, established that brolucizumab can be administered every 3 months while maintaining disease control. CONCLUSIONS: The preclinical and clinical data on brolucizumab provide evidence of sustained disease control with longer injection intervals, thus potentially reducing the treatment burden in patients with nAMD.