Novartis Reports Positive Topline Results from Two Phase III Trials of Beovu® in Diabetic Macular Edema, Demonstrating Non-Inferiority to Aflibercept in Efficacy and Favorable Safety Profile

December 15, 2020 /Bio ValleyBIOON/ --Novartis(Novartis) recently announced the evaluation of the new-generation ophthalmic drug Beovu (brolucizumab) for the treatment ofDiabetesResults of the Phase III KESTREL study on diabetic macular edema (DME). This is the second pivotal Phase III study comparing the efficacy and safety of Beovu versus Eylea (aflibercept) for the treatment of DME, following the pivotal Phase III KITE study. The data showed that the primary endpoint was met during the first year of treatment (52 weeks): Beovu 6 mg demonstrated non-inferiority to aflibercept 2 mg in terms of mean change in best-corrected visual acuity (BCVA). Furthermore, the study also met its key secondary endpoint: Beovu 6 mg demonstrated non-inferiority to aflibercept 2 mg in terms of mean change in BCVA during weeks 40–52. Currently, Beovu is approved for the treatment of wet age-related macular degeneration (wet AMD) at a dose of 6 mg.

During the first year (52 weeks), more than half of the patients in the Beovu (6 mg) treatment group maintained a 3-month dosing interval after the loading phase. From weeks 40 to 52, patients in the Beovu (6 mg) treatment group showed significant improvement in the change from baseline in central subfield thickness (CST), a key indicator of retinal fluid. As Beovu 3 mg did not demonstrate non-inferiority in terms of changes in best-corrected visual acuity (BCVA) in the KESTREL study, confirmatory testing for superiority in anatomical outcomes was not performed. Further analysis of the KESTREL study results is ongoing.In this study, Beovu demonstrated a generally well-tolerated safety profile.

This September,NovartisAnnounced the positive results of the first pivotal Phase 3 KITE study. The results of the KESTREL study supported the positive findings from the KITE study, further demonstrating that Beovu is a potential new treatment for patients with diabetic macular edema (DME).

Data from the KITE and KESTREL studies will be presented at the upcoming medicalMeetingpublished online and will be published in a peer-reviewed journal.NovartisPlans are in place to submit data from the KITE and KESTREL studies to regulatory authorities worldwide in the first half of 2021, with the expectation of collaborating with these agencies to make Beovu available to patients with diabetic macular edema (DME).

NovartisDirk Sauer, Global Head of Ophthalmology at Novartis Pharmaceuticals, stated, “These results indicate that Beovu has the potential to offer improved disease management for patients with diabetic macular edema (DME), if approved. Building on these data and the robust outcomes observed earlier this year from the KITE clinical study, we look forward to collaborating with regulatory authorities to make Beovu available to the DME patient community.”

Currently,NovartisThe comprehensive clinical development program for Beovu is being actively advanced, including wet age-related macular degeneration (wet-AMD), diabetic macular edema (DME), retinal vein occlusion, and proliferativeDiabetesStudy of Retinopathy. The favorable benefit-risk profile of the Beovu development program was approved by the U.S.FDASupport for the review of ongoing research.

DiabetesMacular Edema - DME (Image source: bceye.com)

DME isDiabetesThe leading cause of blindness in patients, affecting 21 million people worldwide, with type 1 diabetes accounting for 12% and type 2 diabetes accounting for 28%.Sustained high blood glucose levels associated with diabetes can damage the small blood vessels in the eyes, causing them to leak fluid. Fluid accumulation in the macula (known as edema) can lead to vision loss. The macula is the area of the retina responsible for clear central vision.Early symptoms of DME include blurred or wavy central vision and distorted color perception, but the disease may also progress asymptomatically in its early stages.

Beovu is a next-generation anti-vascular endothelial growth factor (VEGF) drug, 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 40 countries worldwide. In June this year, the U.S. labeling for Beovu was updated to include additional safety information regarding retinal vasculitis and retinal vascular occlusion.

Wet AMD is a leading cause of blindness, affecting more than 20 million people worldwide; frequent intravitreal injections are a common reason for treatment discontinuation among patients with wet AMD.

Notably, Beovu is the first anti-VEGF agent demonstrating efficacy comparable to Eylea (aflibercept), while maintaining this efficacy with a 3-month dosing interval for maintenance therapy following a 3-month loading phase in eligible patients with wet AMD. By reducing the frequency of injections, it improves patient adherence to treatment, 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 systemic clearance, and favorable drug delivery properties.

The innovative structure of brolucizumab results in a small molecular weight of only 26 kDa, conferring high affinity and potent inhibitory activity against all VEGF-A isoforms. 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 reports positive topline results from second Phase III trial of Beovu® in patients with diabetic macular edema