Novartis Announces Positive Year 2 Results of Phase 3 KESTREL Study of Beovu in Diabetic Macular Edema

Novartis announced the first interpretable results from year 2 (week 100) of the phase 3 KESTREL study. KESTREL assessed the safety and efficacy of Beovu (brolucizumab) 6 mg in patients with visual impairment due to diabetic macular edema (DME). Results from year 2 confirmed the visual acuity gains, fluid reduction findings and safety profile from year one, while addressing the burden of frequent treatments for DME patients.^1,2

Results from year 2 of KESTREL were consistent with those seen at year 1, including maintenance of best-corrected visual acuity (BCVA) and sustained reductions in central subfield thickness (CSFT).^1,2 Additionally, numerically fewer Beovu patients had intraocular fluid and/or sub-retinal fluid (IRF/SRF) versus patients treated with aflibercept.¹ 

More than 40% of Beovu patients were maintained on 12-week dosing intervals, and 70% of patients who completed the first 12-week cycle after loading remained on 12-week dosing through year two, showing the potential for Beovu to offer fluid resolution in more DME patients with fewer injections versus aflibercept.¹

“With an average age at diagnosis of 48 years, DME primarily affects working-age adults, which means managing their vision, in addition to multiple comorbidities related to diabetes, may result in loss of work productivity and employment instability,"^5,6 David M Brown MD, Director of Research, Retina Consultants of Texas, said in a company news release. “The extended dosing and fluid resolution observed in year 2 of the KESTREL clinical trial suggest Beovu has the potential to help appropriate patients more conveniently and effectively manage their disease with dosing intervals every 12 weeks after an initial loading phase.”

Further details of year-2 findings from the KESTREL trial, along with findings from KITE,*another pivotal phase 3 trial of Beovu in DME, will be presented at upcoming medical congresses.

About the KESTREL year 2 safety results

In KESTREL (NCT03481634), rates of intraocular inflammation (IOI) were 4.2% for Beovu 6 mg, 5.3% for Beovu 3 mg, and 1.1% for aflibercept; retinal vasculitis (RV) rates were 0.5% for Beovu 6 mg, 1.6% for Beovu 3 mg and 0% for aflibercept.¹ Rates of retinal vascular occlusion (RO) were 1.6% for both Beovu 6 mg and 3 mg, versus 0.5% for aflibercept.¹ The majority of IOI events were manageable and resolved without any clinical complications.¹ There were no vascular events reported in year 2 (weeks 52-100).¹ No new RV events were reported during year two of KESTREL.¹ Of the four new RO events reported during year 2 (two in Beovu 6 mg, one in Beovu 3 mg and one in aflibercept), none were associated with IOI or RV.¹

Brolucizumab 6 mg is the commercialized dose of Beovu in wet age-related macular degeneration (AMD).⁷ Novartis is committed to bringing Beovu 6 mg to DME patients and has submitted data from KESTREL and KITE (NCT03481660), to global health authorities in H2 2021.

References

1. Data on file. KESTREL (year two) first interpretable results. Novartis, 2021.
2. 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 2021 Annual Meeting. May 2021.
3. Kang SW, Park CY, Ham D-I. The correlation between fluorescein angiographic and optical coherence tomographic features in clinically significant diabetic macular edema. Am J Ophthalmol. 2004;137(2):313-322.
4. Arnold J, Markey CM, Kurstjens NP, Guymer GH. The role of sub-retinal fluid in determining treatment outcomes in patients with neovascular age-related macular degeneration--a phase IV randomised clinical trial with ranibizumab: the FLUID study. BMC Ophthalmol. 2016;143(4):679-680.
5. Petrella RJ, Blouin J, Davies B, Barbeau M. Prevalence, Demographics, and Treatment Characteristics of Visual Impairment due to Diabetic Macular Edema in a Representative Canadian Cohort. J Ophthalmol. 2012;2012:159167.
6. 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.
7. Beovu [US prescribing information] East Hanover, NJ. Novartis Pharmaceuticals Corp; 2020.
8. Data on file. KESTREL clinical trial protocol (CRTH258B2301). Novartis, 2021.
9. Data on file. KITE clinical trial protocol (CRTH258B2302). Novartis, 2021.
10. Romero-Aroca P. Managing diabetic macular edema: The leading cause of diabetes blindness. World J Diabetes. 2011;2(6):98-104.
11. National Eye Institute. Macular Edema. Available at: https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/macular-edema. Accessed December 2021.
12. National Eye Institute. Diabetic Retinopathy. Available at: https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/diabetic-retinopathy. Accessed December 2021.
13. Beovu [summary of product characteristics] Basel, Switzerland. Novartis; 2020.
14. 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 December 2021.
15. 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 December 2021.
16. Beovu [prescription medicine decision summary] Australia. Novartis: 2020.