Novartis Announces FDA Approval of Updated US Label for Beovu® (brolucizumab) to Include Additional Safety Information on Retinal Vasculitis and Retinal Vascular Occlusion

June 12, 2020 /BioValleyBIOON/ -- Novartis recently announced that the U.S. Food and Drug Administration (FDA) has approved the label update for the next-generation ophthalmic drug Beovu (brolucizumab, also known as RTH258), incorporating additional safety information regarding retinal vasculitis and retinal vascular occlusion.

This approval marks the first label update approval obtained since Novartis previously issued a notice stating that, following review and further analysis of rare post-marketing safety events reported to Novartis, the product label would be updated globally. This isNovartisAs part of the numerous efforts to help ophthalmologists make informed decisions regarding the use of Beovu, a dedicated internal team has been established to collaborate with top global experts (a consortium) to investigate root causes, risk factors, mitigation measures, and potential treatment strategies.

This update to the US labeling includes the addition of a subsection under “Warnings and Precautions” (Section 5) specifically addressing retinal vasculitis and/or retinal vascular occlusion. The update also clearly states that theseAdverse Reactionsis part of the intraocular inflammation rate profile from the Phase III HAWK and HARRIER trials (Table 1).

NovartisMarcia Kayath, Global Head of Medical Affairs and Chief Medical Officer at Novartis, stated: “This label update provides clinicians with critical information to guide treatment decisions. We believe that Beovu remains an important therapeutic option for patients with wet AMD, offering a favorable overall benefit-risk profile. We remain grateful to all physicians who have taken the time to share their expertise and treatment experiences, contributing to the collective understanding of these safety events. As we work to identify the root causes and potential mitigation strategies, we will continue to communicate our findings to regulatory authorities and healthcare providers in a transparent and timely manner.”

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

Wet AMD is a leading cause of blindness, affecting more than 20 million people worldwide. Frequent intravitreal injections are a common reason for patients with wet AMD to discontinue treatment. Beovu is the first anti-VEGF drug whose efficacy is comparable to that of Regeneron’s blockbuster ophthalmic product Eylea (aflibercept). In eligible patients with wet AMD, maintaining a three-month dosing interval after the initial three-month loading phase does not compromise efficacy. By reducing the frequency of injections, Beovu improves patient adherence to treatment, thereby effectively preserving vision.

Beovu Receives Regulatory Approval Based on Phase III HAWK and HARRIERClinical Trialresults. The data showed that Beovu demonstrated non-inferiority to Regeneron’s ophthalmic product Eylea (aflibercept) in terms of the mean change in best-corrected visual acuity (BCVA) during the first year of treatment (Week 48). Furthermore, Beovu exhibited superiority over Eylea in three secondary endpoints representing key indicators of disease progression, including: disease activity, central subfield retinal thickness, and retinal fluid (intraretinal and/or subretinal fluid). Importantly, Beovu demonstrated the ability to maintain a 3-month dosing interval immediately following the loading phase in the majority of patients.

In early 2020,NovartisFollowing the receipt of rare post-marketing reports of vasculitis (including retinal occlusive vasculitis), an internal review of these post-marketing safety case reports was initiated, including the establishment of an external Safety Review Committee (SRC) to conduct an independent and objective assessment of these cases and compare them with the intraocular inflammatory events observed in the Beovu Phase III trials (HAWK and HARRIER).

SRC recently released a report presenting an independent analysis of adverse events from the HAWK and HARRIER trials, identifying cases similar to those reported in post-marketing surveillance. The report also noted that although adverse events of retinal vasculitis/retinal vascular occlusion were associated with a risk of vision loss, the overall incidence of vision loss in the study population was similar between the Beovu and Eylea treatment groups.

Novartis will continue to collaborate with regulatory authorities worldwide to initiate safety information updates, thereby facilitating global updates to the prescribing information for Beovu. To date, Beovu has been approved in more than 30 countries. Recently, Beovu has received positive health technology assessment (HTA) reviews in countries such as Canada, and it is now fully reimbursed in multiple countries, including Japan and Switzerland.NovartisWe still believe that Beovu is an important treatment option for patients with wet AMD.

The active pharmaceutical ingredient of Beovu is brolucizumab (RTH258), a humanized single-chain antibody fragment (scFv) that targets all isoforms 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 weight 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: USFDA approves updated Novartis Beovu® label, to include additional safety information