Novartis Announces FDA and EMA Filing Acceptances of Beovu for Patients with Diabetic Macular Edema

Novartis announced that the FDA has accepted the company’s supplemental biologics license application (BLA) 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 (AMD) in October 2019 (FDA) and February 2020 (European Commission).^5,6 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.¹ Consistently high blood sugar levels associated with diabetes can damage small blood vessels in the eye, causing them to leak fluid.¹ Unmet needs in DME include improving fluid resolution and addressing the burden of frequent treatment schedules.^1-3

“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 3, randomized, double-masked KESTREL and KITE studies, which met their primary endpoint of noninferiority in change in best corrected visual acuity (BCVA) from baseline versus aflibercept at year one.⁴ 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.⁴ Fewer eyes treated with Beovu had intraretinal and/or subretinal fluid (IRF/SRF) at week 32 and week 52 versus eyes treated with aflibercept.⁴ The KESTREL and KITE trials are the first pivotal trials to assess an anti-VEGF treatment on 6-week dosing intervals in the loading phase, suggesting Beovu may offer fewer injections from the start of treatment.⁴ 

Overall, Beovu demonstrated a favorable benefit-risk profile in KESTREL and KITE.⁴ The most common ocular and non-ocular adverse events (≥5%) in KESTREL and KITE were conjunctival hemorrhage, nasopharyngitis, and hypertension.⁴ 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 mg.⁴ IOI rates in KITE were equivalent (1.7%) between the Beovu 6 mg and aflibercept 2 mg arms with no retinal vasculitis reported.⁴ 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).⁴ The majority of these events were manageable and resolved with or without treatment.⁴

About the KESTREL and KITE clinical trials

KESTREL and KITE are global, randomized, double-masked, phase 3, 2-year studies comparing the safety and efficacy of Beovu and aflibercept in the treatment of DME.^4,7,8

KESTREL and KITE involved 926 patients in 36 countries.^7,8 In the loading phase of both trials, patients in the Beovu arms were treated every 6 weeks for a total of five doses; patients in the aflibercept arms were treated every 4 weeks for a total of five doses, in line with its label at the start of the studies.^7.8 Following the loading phase, patients in the Beovu arms were subsequently treated every 12 weeks, with those demonstrating disease activity moved to dosing every 8 weeks for the remainder of the study.^7,8

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.⁸ As in year 1, those demonstrating disease activity were moved to dosing every eight weeks for the remainder of the study.⁸ Through the entirety of both 2-year trials, patients in the aflibercept arms were treated every eight weeks.^7,8

References

1. Romero-Aroca P. Managing diabetic macular edema: The leading cause of diabetes blindness. World J Diabetes. 2011;2(6):98-104.
2. Browning DJ, Stewart MW, Lee C. Diabetic macular edema: Evidence-based management. Indian J Ophthalmol. 2018;66(12):1736-1750. 
3. Kiss S, Chandwani HS, Cole AL, Patel VD, Lunacsek OE, Dugel PU. Comorbidity and health care visit burden in working-age commercially insured patients with diabetic macular edema. Clin Ophthalmol. 2016;10:2443-2453.
4. Brown D, Wolf S, Garweg JG, et al. Brolucizumab for the treatment of visual impairment due to diabetic macular edema: 52-week results from the KESTREL & KITE studies. Presented at: The Association for Research in Vision and Ophthalmology (ARVO) 2021 Annual Meeting. May 2021.
5. Beovu [US prescribing information] East Hanover, NJ. Novartis: 2020.
6. Beovu [summary of product characteristics] Basel, Switzerland. Novartis: 2020.
7. Data on file. KESTREL clinical trial protocol (CRTH258B2301). Novartis, 2021.
8. Data on file. KITE clinical trial protocol (CRTH258B2302). Novartis, 2021.
9. National Eye Institute. Macular Edema. Available at: https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/macular-edema. Accessed October 2021.
10. National Eye Institute. Diabetic Retinopathy. Available at: https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/diabetic-retinopathy. Accessed October 2021.
11. Pharma Japan. National Health Insurance Pricing. Available at: https://pj.jiho.jp/sites/default/files/pj/document/2020/05/New%20Drugs%20to%20Be%20Added%20to%20NHI%20Price%20List%20on%20May%2020_1.pdf. Accessed October 2021.
12. Canadian Agency for Drugs and Technologies in Health. CADTH Canadian Drug Expert Committee Recommendation. Available at: https://cadth.ca/sites/default/files/cdr/complete/SR0632%20Beovu%20-%20CDEC%20Final%20Recommendation%20%E2%80%93%20May%2025%2C%202020_for%20posting.pdf. Accessed October 2021.
13. Beovu [prescription medicine decision summary] Australia. Novartis: 2020.