Novartis Receives EU Approval for Beovu (Brolucizumab): A Next-Generation Anti-VEGF Therapy for Wet AMD with Quarterly Dosing

February 18, 2020 News /BioValleyBIOON/ --NovartisNovartis recently announced that the European Commission (EC) has approved Beovu (brolucizumab, also known as RTH258), a next-generation ophthalmic drug, for the treatment of wet age-related macular degeneration (wet AMD, also known as neovascular AMD or nAMD). This approval applies to all 27 EU member states, as well as the United Kingdom, Iceland, Norway, and Liechtenstein. In the EU, an estimated 1.7 million people are affected by wet AMD, which is the leading cause of severe vision loss and blindness in individuals aged 65 and older.

Beovu is a next-generation anti-vascular endothelial growth factor (VEGF) drug, approved in the United States in October 2019 for the treatment of wet AMD. Notably, Novartis used a Priority Review Voucher (PRV) to accelerate the U.S. regulatory review of Beovu, shortening the review period from the standard 10 months to 6 months. In January 2020, Beovu also received approval in Switzerland and Australia.NovartisCommitted to bringing Beovu to patients worldwide, Beovu is currently under review by regulatory authorities in Canada, Japan, and Brazil.

Wet AMD is a leading cause of blindness, affecting more than 20 million people worldwide. Frequent injections are a common reason for patients with wet AMD to discontinue treatment. In the United States and the European Union, Beovu is the first anti-VEGF drug approved by regulators that demonstrates greater reduction in retinal fluid compared to Regeneron’s blockbuster ophthalmic product Eylea (aflibercept). In eligible patients with wet AMD, Beovu maintains efficacy with a dosing interval of once every three months following a three-month loading phase. By reducing the frequency of injections, Beovu improves patient adherence to treatment, thereby effectively preserving vision.

Existing labels for ophthalmic therapeutic products indicate that a dosing regimen administered every 12 weeks (3 months) yields suboptimal efficacy. Beovu is the first drug to offer a reduced dosing frequency while maintaining therapeutic effectiveness during the first year of treatment, thereby allowing patients with wet age-related macular degeneration (AMD) more time to focus on what matters most in their lives.

Marie France Tschudin, President of Novartis Pharmaceuticals, stated, “Patients with wet AMD are often elderly and may face significant challenges in managing their disease. We believe that Beovu and its ability to reduce retinal fluid will deliver substantial therapeutic value, helping physicians optimize patient treatment based on disease activity. With the approval of this innovative biologic,”Novartis"Continuing to reimagine treatment options for patients with wet AMD."

Wet AMD (wet-AMD, image source: retinaboston.com)

This approval is based on data from the Phase III HAWK (NCT02307682) and HARRIER (NCT02434328) studies. These two studies are the first and only global head-to-head clinical trials to prospectively demonstrate the significant efficacy of initiating Beovu treatment with a dosing regimen of once every 12 weeks (once every 3 months) in patients with wet AMD. Both studies were prospective, randomized, double-blind, multicenter trials conducted in patients with wet AMD to evaluate the efficacy and safety of Beovu versus Eylea. In both studies, eligible patients could receive maintenance therapy with a 3-month dosing interval immediately following the loading phase.

The results showed that both studies met their primary endpoints. In the first year of treatment (Week 48), Beovu (6 mg) demonstrated non-inferiority to Eylea in improving visual acuity. Specifically, in the HAWK and HARRIER studies, the mean change from baseline in best-corrected visual acuity (BCVA) for the Beovu (6 mg) treatment groups was +6.6 letters (compared with +6.8 letters in the Eylea group) and +6.9 letters (compared with +7.6 letters in the Eylea group), respectively. In both studies, approximately 30% of patients in the Beovu treatment groups achieved a BCVA improvement of at least 15 letters at one year.

Furthermore, Beovu (6 mg) demonstrated superiority in three secondary endpoints related to key indicators of disease progression: disease activity, central subfield retinal thickness, and retinal fluid (intraretinal fluid and/or subretinal fluid). The specific data are as follows: (1) At Week 16 and Year 1, the proportion of patients with disease activity was lower in the Beovu (6 mg) group than in the Eylea group (Week 16 [HAWK study: 24.0% vs. 34.5%, p=0.001; HARRIER study: 22.7% vs. 32.2%, p=0.002]; Year 1 [HAWK study: 23.5% vs. 33.5%, p=0.002; HARRIER study: 21.9% vs. 31.4%, p=0.002]); (2) At Week 16 and Year 1, the proportion of patients with intraretinal fluid (IRF) and/or subretinal fluid (SRF) was significantly reduced in the Beovu (6 mg) group compared with the Eylea group (Week 16: a 35% reduction in both the HAWK and HARRIER studies; Year 1: a 30% reduction in the HAWK study and a 41% reduction in the HARRIER study); (3) At Year 1, the Beovu group showed a significantly greater reduction from baseline in central subfield retinal thickness compared with the Eylea group (HAWK study: LS mean −172.8 μm vs. −143.7 μm, p=0.001; HARRIER study: LS mean −193.8 μm vs. −143.9 μm, p<0.001). Anatomical retinal fluid outcomes indicated that Beovu was superior to Eylea.

Furthermore, in the first year, more than half of the patients in the Beovu (6 mg) treatment group maintained a 3-month dosing interval (56% in the HAWK study and 51% in the HARRIER study). Among patients in the Beovu (6 mg) group who initiated the 3-month dosing regimen after the loading phase, 85% (HAWK study) and 82% (HARRIER study) maintained this dosing interval during the first year. The safety profile of Beovu was generally comparable to that of Eylea in these studies.

The active pharmaceutical ingredient of Beovu is brolucizumab (RTH258), a humanized single-chain antibody fragment (scFv) that targets all forms of vascular endothelial growth factor-A (VEGF-A). Single-chain antibody fragments have garnered significant attention in drug development due to their small size, enhanced tissue penetration, rapid systemic clearance, and favorable drug delivery properties.

Brolucizumab’s innovative structure results in a small molecular size of only 26 kDa, conferring potent inhibitory activity against all VEGF-A isoforms with high affinity. In preclinical studies, brolucizumab inhibited VEGF receptor activation by blocking ligand-receptor interactions. Increased signaling through the VEGF pathway is associated with pathological ocular angiogenesis and retinal edema. In patients with chorioretinal vascular diseases, inhibition of the VEGF pathway suppresses the growth of neovascular lesions, alleviates retinal edema, and improves visual acuity. (Bioon.com)

Original Source: Novartis receives ECapproval for Beovu®, a next-generation anti-VEGF treatment for wet AMD, a leading cause of blindness worldwide