Novartis announced yesterday that the U.S. Food and Drug Administration (FDA) accepted the company's Biologics License Application (BLA) for brolucizumab (RTH258) for the treatment of wet age-related macular degeneration (AMD), also known as neovascular AMD. Novartis used a priority review voucher to expedite FDA review to make brolucizumab available as quickly as possible. If approved, Novartis anticipates launching brolucizumab by the end of 2019.
The regulatory application is primarily based on Phase III data from the HAWK (NCT02307682) and HARRIER (NCT02434328) trials — prospective, randomized, double-masked multi-center studies, enrolling more than 1,800 patients across nearly 400 sites worldwide. The studies were designed to compare the efficacy and safety of intravitreal injections of brolucizumab 6 mg (HAWK and HARRIER) and 3 mg (HAWK only) versus aflibercept 2 mg in patients with AMD. In both trials, patients were randomized to either brolucizumab or aflibercept. Immediately following the 3-month loading phase, patients in the brolucizumab arms received a q12w dosing interval with an option to adjust to a q8w dosing interval based on masked disease activity assessments at defined visits. Aflibercept was dosed bi-monthly according to its label at the time of study initiation.
Brolucizumab met the primary efficacy objective of non-inferiority versus aflibercept in mean change in best-corrected visual acuity (BCVA) from baseline to week 48 with high statistical significance. Additionally, brolucizumab demonstrated superiority in three secondary endpoints considered key parameters of AMD: central subfield retinal thickness, retinal fluid (intraretinal fluid and/or subretinal fluid) and disease activity.
Brolucizumab (RTH258) is a humanized single-chain antibody fragment (scFv). Single-chain antibody fragments are highly sought after in drug development due to their small size, enhanced tissue penetration, rapid clearance from systemic circulation and drug delivery characteristics. The proprietary structure is a potent inhibitor of all VEGF-A isoforms, which are associated with pathologic ocular angiogenesis and retinal edema. In preclinical studies, brolucizumab inhibited activation of VEGF receptors through prevention of the ligand-receptor interaction. Inhibition of the VEGF pathway has been shown to inhibit the growth of neovascular lesions, resolve retinal edema and improve vision in patients with chorioretinal vascular diseases.
Full news release: https://www.prnewswire.com/news-releases/novartis-announces-fda-filing-acceptance-and-priority-review-of-brolucizumab-rth258-for-patients-with-wet-amd-300832296.html