US FDA & EMA accepts Novartis’ sBLA for Beovu to treat diabetic macular edema

BaselThursday, October 14, 2021, 09:00 Hrs  [IST]

Novartis announced that the US Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) and that the European Medicines Agency (EMA) has validated the type-II variation application for Beovu (brolucizumab) 6 mg for the treatment of diabetic macular edema (DME). Additionally, the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) accepted an application for Beovu in the treatment of DME. Regulatory decisions for Beovu in DME are expected in mid-2022 for the US and Europe.

If approved, DME would be the second indication for Beovu following its approval for wet age-related macular degeneration in October 2019 (FDA) and February 2020 (European Commission). DME is the leading cause of blindness in adults in developed countries, affecting 12% of people with type 1 diabetes and 28% of those with type 2 diabetes. Consistently high blood sugar levels associated with diabetes can damage small blood vessels in the eye, causing them to leak fluid. Unmet needs in DME include improving fluid resolution and addressing the burden of frequent treatment schedules.

“People living with diabetes often need to manage multiple comorbidities related to diabetes and there is a significant need to provide better disease management. If approved, Beovu has the potential to provide better fluid resolution and fewer injections during the loading phase and throughout maintenance treatment,” said Jill Hopkins, SVP and global development unit head, Ophthalmology, Novartis Pharmaceuticals. “We look forward to bringing this potential new treatment option that may help to address unmet needs in the DME patient population.”

The regulatory applications are based on year one data from the Phase III, randomized, double-masked KESTREL and KITE studies, which met their primary endpoint of non-inferiority in change in best corrected visual acuity (BCVA) from baseline versus aflibercept at year one. In KESTREL and KITE, following the loading phase, over half of patients in the Beovu 6 mg arm remained on a 12-week dosing interval through year one. Fewer eyes treated with Beovu had intraretinal and/or subretinal fluid (IRF/SRF) at week 32 and week 52 versus eyes treated with aflibercept4. The KESTREL and KITE trials are the first pivotal trials to assess an anti-VEGF treatment on six-week dosing intervals in the loading phase, suggesting Beovu may offer fewer injections from the start of treatment.

Overall, Beovu demonstrated a favorable benefit-risk profile in KESTREL and KITE. The most common ocular and non-ocular adverse events (=5%) in KESTREL and KITE were conjunctival hemorrhage, nasopharyngitis and hypertension. IOI rates in KESTREL were 4.7% for brolucizumab 3 mg (including 1.6% retinal vasculitis), 3.7% for Beovu 6 mg (including 0.5% retinal vasculitis), and 0.5% for aflibercept 2 mg4. IOI rates in KITE were equivalent (1.7%) between the Beovu 6 mg and aflibercept 2 mg arms with no retinal vasculitis reported4. Retinal vascular occlusion was reported in KESTREL for brolucizumab 3 mg (1.1%) and 6 mg (0.5%), and in KITE for brolucizumab and aflibercept (0.6% each). The majority of these events were manageable and resolved with or without treatment.

Novartis remains committed to bringing Beovu to the patients who may benefit most from this important medicine.

KESTREL and KITE are global, randomized, double-masked, phase III, two-year studies comparing the safety and efficacy of Beovu and aflibercept in the treatment of DME.

KESTREL and KITE involved 926 patients in 36 countries. In the loading phase of both trials, patients in the Beovu arms were treated every six weeks for a total of five doses; patients in the aflibercept arms were treated every four weeks for a total of five doses, in line with its label at the start of the studies. Following the loading phase, patients in the Beovu arms were subsequently treated every 12 weeks, with those demonstrating disease activity moved to dosing every eight weeks for the remainder of the study.

At week 72 of KITE, Beovu patients dosed every 12 weeks could be extended to dosing every 16 weeks, and patients dosed every eight weeks could be extended to every 12 weeks. As in year one, those demonstrating disease activity were moved to dosing every eight weeks for the remainder of the study. Through the entirety of both two-year trials, patients in the aflibercept arms were treated every eight weeks.

Beovu (brolucizumab, also known as RTH258) 6 mg is approved for the treatment of wet age-related macular degeneration (AMD) in more than 70 countries, including in the US, EU, UK, Japan, Canada and Australia. Additional trials, which study the effects of brolucizumab in patients with wet AMD, diabetic macular edema (DME), and proliferative diabetic retinopathy (PDR), are currently ongoing.