Novartis Reports Preliminary Findings from Consortium Investigation into Retinal Adverse Events with Beovu in Wet AMD

November 16, 2020 /BioonBIOON/ -- Novartis recently announced preliminary results from a joint investigation into key issues related to the use of its next-generation ophthalmic drug, Beovu (brolucizumab), in adult patients with wet age-related macular degeneration (wet AMD). At the 2020 Annual Meeting of the American Academy of Ophthalmology (AAO), analyses of U.S. real-world data and Phase III clinical trial data identified that baseline patient characteristics may be associated with the incidence of inflammation-related adverse events following Beovu treatment.NovartisA comprehensive work plan is underway to investigate the root causes and potential risk factors of these events, and to identify mitigation strategies and treatment protocols.

Analysis of data from the IRIS Registry (including 12,000 patients treated with Beovu) revealed that the highest observed risk of retinal vasculitis (RV) and/or retinal vascular occlusion (RO) within six months after the first Beovu injection occurred in patients who had experienced intraocular inflammation (IOI) and/or RO within the 12 months prior to their first Beovu injection. The overall incidence rate of RV/RO among all Beovu-treated patients in the IRIS Registry was 0.46%, increasing to 3.97% in patients with a history of IOI and/or RO.

NovartisMarcia Kayath, Global Head of Medical Affairs and Chief Medical Officer at Novartis, stated, “We are pleased to share these findings, which underscore the importance of carefully evaluating patients for active intraocular inflammation prior to initiating Beovu therapy and throughout the treatment course. Despite significant advances in the treatment of wet age-related macular degeneration (AMD), data show that 50% of patients still have retinal fluid and one-third require monthly injections, highlighting a substantial unmet medical need that Beovu has the potential to address.”

In a post hoc unblinded assessment of the Phase III HAWK and HARRIER data, a trend toward an increased incidence of retinal vasculitis/retinal vascular occlusion (RV/RO) was observed in patients who developed treatment-emergent (enhanced/pre-existing) anti-drug antibodies (ADAs). Currently,NovartisFurther analysis of the provided data is underway, and additional data are being collected.

Furthermore, the results also showed that, compared with Eylea (aflibercept), Beovu was associated with a greater and sustained reduction in pigment epithelial detachments and subretinal hyper-reflective material.

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

According to HAWK and HARRIERClinical TrialsAs a result, Beovu has been approved in more than 50 countries, including the United States, the European Union, the United Kingdom, Japan, Canada, and Australia.NovartisBeovu remains an important treatment option for patients with wet AMD, with a favorable benefit-risk profile.

Beovu is a next-generation anti-vascular endothelial growth factor (VEGF) drug that was approved in the United States in October 2019 and in the European Union in February 2020 for the treatment of wet age-related macular degeneration (wet AMD). To date, Beovu has been approved for marketing in more than 50 countries worldwide.

In early 2020, following post-marketing reports of vasculitis, Novartis initiated a review of post-marketing safety case reports and, together with an external review committee, confirmed a safety signal for a rare adverse event termed “retinal vasculitis (RV)” and/or “retinal vascular occlusion (RO),” which may lead to severe vision loss. Therefore,NovartisInitiated global label updates to reflect this adverse event information.In June this year, the US label for Beovu was updated to include additional safety information regarding RV and RO.

Wet AMD is a leading cause of blindness, affecting more than 20 million people worldwide. Frequent intravitreal injections are a common reason for wet AMD patients to discontinue treatment.

Notably, Beovu is the first anti-VEGF agent with efficacy comparable to Eylea (aflibercept) that allows for a 3-month maintenance dosing interval following a 3-month loading phase in eligible patients with wet AMD, without compromising efficacy. This regimen improves patient adherence by reducing the frequency of injections, thereby effectively preserving visual acuity.

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 clearance from systemic circulation, and favorable drug delivery properties.

Brolucizumab’s innovative structure gives it a small size of only 26 kDa, potent inhibitory activity against all VEGF-A isoforms, and high affinity. In preclinical studies, brolucizumab inhibited the activation of VEGF receptors 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: Results from Real-World Data and Post-Hoc Analysis of Novartis Beovu® Pivotal Trials Presented at AAO 2020