VCBeat Health Contact Us
Home Novartis Announces Regulatory Submissions of Beovu® (brolucizumab) for Diabetic Macular Edema in the US, EU, and Japan

Novartis Announces Regulatory Submissions of Beovu® (brolucizumab) for Diabetic Macular Edema in the US, EU, and Japan

Oct 15, 2021 04:08 CST Updated 04:08
Novartis

Drug Development and Manufacturing

FDA

U.S. Food and Drug Administration

European Medicines Agency

The European Medicines Agency (EMA) is a decentralized agency of the European Union (EU), located in London. It began operations in 1995. The agency is responsible for the scientific evaluation, supervision, and safety monitoring of medicines developed by pharmaceutical companies for use in the EU. By ensuring that all medicines available on the EU market are safe, effective, and of high quality, the EMA protects public and animal health in the 28 EU Member States and countries of the European Economic Area.

PMDA

The PMDA is responsible for preventing adverse reactions to pharmaceuticals and biologics, as well as conducting timely assessments and responses to such risks, thereby helping to enhance the quality, efficacy, and safety of medicinal products and improve public health. Its scope of work includes providing relief for adverse drug reactions, reviewing pharmaceuticals, medical devices, and related businesses in accordance with the law, ensuring the safety of pharmaceuticals and medical devices, and disseminating information on safety measures and medical products.


Diabetes MellitusMacular Edema - DME (Image source: bceye.com)

October 13, 2021 News /BioonBIOON/ --Novartis(Novartis) recently announced that the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), Japan Pharmaceutical andMedical DevicesThe Pharmaceuticals and Medical Devices Agency (PMDA) has accepted applications for the next-generation ophthalmic drug BBeovu (brolucizumab, 6 mg) TreatmentDiabetes mellitusDiabetic Macular Edema (DME)application. Regulatory decisions regarding Beovu for the treatment of DME in the United States and the European Union are expected by mid-2022.

If approved, DME will become the second indication for Beovu following its approval for the treatment of wet age-related macular degeneration (wet-AMD) in October 2019 (US) and February 2020 (EU). In developed countries, DME is the leading cause of blindness in adults, affecting 12% of type 1Diabetes mellituspatients and 28% of type 2# Diabetes mellitusPatients. Chronic hyperglycemia associated with diabetes damages the small blood vessels in the eye, leading to fluid leakage. Unmet medical needs in DME include resolution of retinal fluid and addressing the burden of frequent injections.

The application for Beovu in the treatment of DME, based on two randomized, double-blind, double-dummy Phase 3 trials evaluating Beovu (brolucizumab, 6 mg) versus Eylea (aflibercept, 2 mg) for the treatment of DME.Clinical Trial(KESTREL, KITE) one-year data. Both trials met the primary endpoint:The change from baseline in best-corrected visual acuity (BCVA) for patients in the Beovu treatment group was non-inferior to that in the Eylea treatment group.. In the 2 trials, after the loading phase,In the Beovu 6 mg group, more than half of the patients maintained a 12-week dosing interval through to one year.. Compared with eyes treated with Eylea, eyes treated with Beovu developed at Week 32 and Week 52Less intraretinal and/or subretinal fluid (IRF/SRF)。

KESTREL and KITE are the first pivotal trials evaluating an anti-VEGF drug with a 6-week dosing interval during the loading phase.Clinical Trial, data indicate that Beovu may require fewer injections from treatment initiation.

In terms of safety, overall, Beovu demonstrated a favorable benefit-risk profile in 2 trials. The most common ocular and non-ocular adverse events (≥5%) were conjunctival hemorrhage, nasopharyngitis,# Hypertension。In the KESTREL trial, the incidence of intraocular inflammation (IOI) was 4.7% in the Beovu 3 mg group (including 1.6% retinal vasculitis), 3.7% in the Beovu 6 mg group (including 0.5% retinal vasculitis), and 0.5% in the Eylea 2 mg group. In the KITE trial, the incidence of IOI was comparable between the Beovu 6 mg group and the Eylea 2 mg group (1.7%), with no retinal vasculitis reported. Retinal vascular occlusion was reported in both the KESTREL trial (1.1% in the Beovu 3 mg group and 0.5% in the Beovu 6 mg group) and the KITE trial (0.6% in the Beovu group and 0.6% in the Eylea group). Most of these events were manageable and resolved with or without treatment.

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

DME is a leading cause of blindness in patients with diabetes, affecting 21 million people worldwide, with a prevalence of 12% in patients with type 1 diabetes and 28% in patients with type 2 diabetes. Persistently elevated blood glucose levels associated with diabetes can damage the small blood vessels in the eye, causing them to leak fluid. Fluid accumulation in the macula (known as edema) leads to vision loss. The macula is the region of the retina responsible for sharp central vision. Early symptoms of DME include blurry or wavy central vision and distorted color perception; however, the disease may also progress asymptomatically in its early stages.

BEovu is a next-generation anti-vascular endothelial growth factor (VEGF) drug., was approved in the United States in October 2019 and in the European Union in February 2020, forTreatment of wet age-related macular degeneration (wet-AMD). To date, Beovu has been approved for marketing in over 40 countries worldwide. In June 2020, the US label for Beovu was updated to include additional safety information regarding retinal vasculitis (RV) and retinal vascular occlusion (RO).

Wet age-related macular degeneration (wet-AMD, nAMD) is a leading cause of blindness, affecting over 20 million people worldwide, and frequent intravitreal injections are a common reason for treatment discontinuation among wet-AMD patients. Notably,Beovu is the first anti-VEGF agent with efficacy comparable to Eylea (aflibercept) that, in eligible patients with wet AMD, maintains efficacy without compromise when administered at 3-month dosing intervals for maintenance therapy following a 3-month loading phase. By reducing the frequency of injections, it improves patient treatment adherence, thereby effectively maintaining patients' vision.

The active pharmaceutical ingredient in Beovu is brolucizumab (RTH258), which is aHumanized single-chain antibody fragment (scFv), targeting all isoforms of vascular endothelial growth factor-A (VEGF-A). Single-chain antibody fragments have attracted significant attention in drug development due to their small size, enhanced tissue penetration, rapid clearance from systemic circulation, and drug delivery characteristics.

The novel structure of brolucizumab results in a molecular weight of only 26 kDa, exhibiting potent inhibition and high affinity for all isoforms of VEGF-A. In preclinical studies, brolucizumab inhibits VEGF receptor activation by blocking ligand-receptor interactions. Increased VEGF pathway signaling 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, reduces retinal edema, and improves visual acuity.

In China, Beovu has entered Phase III clinical trials for the development of indications such as wet age-related macular degeneration (AMD) and diabetic retinopathy. Notably, in April 2021, during the "Never-Ending" International Innovative Drugs and Medical Devices Exhibition, the first injection of Beovu for the treatment of wet AMD in China was administered at Hainan Boao Super Hospital. Beovu is currently the first globally approved anti-vascular endothelial growth factor (anti-VEGF) drug that can be administered once every three months following a loading dose phase. (Bioon.com)