Novartis announces FDA and EMA filing acceptances of Beovu® for patients with diabetic macular edema

Oct 13, 2021
  • Regulatory decisions for Beovu (brolucizumab) in diabetic macular edema (DME) are expected in mid-2022 in the US and Europe
  • DME is the leading cause of blindness in adults in developed countries; unmet needs in DME include improving fluid resolution and addressing the burden of frequent treatment schedules1-3
  • The regulatory applications are based on year one data from the Phase III KESTREL and KITE trials investigating Beovu 6 mg versus aflibercept 2 mg in DME patients4
  • In KESTREL and KITE, Beovu was non-inferior to aflibercept in change in BCVA from baseline and showed potential for fluid resolution in more DME patients with fewer injections4
  • Beovu demonstrated a favorable benefit-risk profile in KESTREL and KITE4
  • The Japanese PMDA also accepted an application for Beovu in DME

Basel, October 13, 2021 — Novartis today 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)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 diabetes1. Consistently high blood sugar levels associated with diabetes can damage small blood vessels in the eye, causing them to leak fluid1. Unmet needs in DME include improving fluid resolution and addressing the burden of frequent treatment schedules1-3.

“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 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 one4. 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 one4. 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 treatment4.

Overall, Beovu demonstrated a favorable benefit-risk profile in KESTREL and KITE4. The most common ocular and non-ocular adverse events (≥5%) in KESTREL and KITE were conjunctival hemorrhage, nasopharyngitis and hypertension4. 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)4. The majority of these events were manageable and resolved with or without treatment4.

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

About the KESTREL and KITE clinical trials
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 DME4,7,8.

KESTREL and KITE involved 926 patients in 36 countries7,8. 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 studies7.8. Following the loading phase, patients in the Beovu arms were subsequently treated every 12 weeks, with those demonstrating disease activity moved to dosing every eight weeks for the remainder of the study7,8.

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 weeks8. As in year one, those demonstrating disease activity were moved to dosing every eight weeks for the remainder of the study8. Through the entirety of both two-year trials, patients in the aflibercept arms were treated every eight weeks7,8.

About diabetic macular edema (DME)
DME is a common microvascular complication in patients with diabetes that may have a debilitating impact on visual acuity, eventually leading to blindness1. DME is the leading cause of blindness in adults in developed countries, affecting 12% of patients with type 1 diabetes and 28% of those with type 2 diabetes1.

Consistently high blood sugar levels associated with diabetes can damage small blood vessels in the eye, causing them to leak fluid1. This damage leads to an excess of vascular endothelial growth factor (VEGF)1,9. VEGF is a protein that stimulates the growth of blood vessels1,9. At elevated levels in DME, VEGF stimulates the growth of abnormal, leaky blood vessels1,9. The resulting accumulation of fluid (known as edema) in the macula can lead to vision loss1,9. The macula is the area of the retina responsible for sharp, central vision9. Early symptoms of DME include blurry or wavy central vision and distorted color perception, although the disease can also progress without symptoms at early stages9,10.

About Beovu (brolucizumab) 6 mg
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 Australia5,6,11-13. 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.

About Novartis in Ophthalmology
At Novartis, our mission is to discover new ways to improve and extend people's lives. In ophthalmology, we develop and deliver life-changing medicines and therapies for diseases and conditions from front to back of the eye, enabled by data and transformative technologies. Our ophthalmic solutions reach more than 150M people per year, from premature infants to the elderly.

*Kite Pharma, Inc. is neither a sponsor of nor associated with Novartis’ KITE trial.

Disclaimer
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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.

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