Beovu obtains DME indication in Europe

The European Commission (EC) has approved anti-VEGF therapy Beovu (brolucizumab) 6 mg for diabetic macular edema (DME), marking the therapy’s second indication in the bloc.

Ophthalmic pharmaceutical giant Novartis announced the clearance on 31 March that applied to all 27 European Union (EU) member states as well as Iceland, Norway and Liechtenstein.

It comes after Beovu was first approved for neovascular age-related macular degeneration (nAMD) in Europe in 2020. It’s also indicated for this disease in Australia where it has been listed on the Pharmaceutical Benefits Scheme (PBS) as a second-line treatment.

The EC approval was based on year one data from the Phase 3, randomised, 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 (Eylea) at year one, Novartis stated.

In both trials, following the loading phase, over half of patients (55.1% in KESTREL and 50.3% in KITE) in the Beovu 6 mg arm remained on a 12-week dosing interval through year one.

Aflibercept dosing was aligned to the approved EU label in year one of treatment. In aggregate, a numerically lower proportion of patient eyes treated with Beovu had intraretinal fluid, subretinal fluid or both at week 52 versus eyes treated with aflibercept (in KESTREL 60.3% in Beovu arm versus 73.3% in aflibercept arm; in KITE 54.2% versus 72.9%, respectively; testing for statistical significance was not performed)².

Per the approved prescribing information, following the loading phase of five doses injected six weeks apart, physicians may individualise treatment for DME patients based on their disease activity, as assessed by vision and fluid-related parameters³.

In patients without disease activity, physicians should consider 12-week intervals between Beovu treatments; in patients with disease activity, physicians should consider eight-week intervals between treatments³.

“This approval marks a significant milestone for DME patients, many of whom are of working age and struggle with adherence due to the need to manage multiple comorbidities related to diabetes,” said Ms Jill Hopkins, senior vice president and global development unit head of ophthalmology at Novartis Pharmaceuticals.

“KESTREL and KITE were the first pivotal trials to assess an anti-VEGF on six-week dosing intervals in the loading phase, suggesting Beovu may offer fewer injections from the start of treatment through year one.* The EC approval of Beovu in DME may thus help address unmet needs.”

Pursuing DME indication in other markets

The most common ocular and non-ocular adverse events (≥5%) at year one in KESTREL and KITE were conjunctival hemorrhage, nasopharyngitis and hypertension². Intraocular inflammation (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 mg².

IOI rates in KITE were equivalent (1.7%) between the Beovu 6 mg and aflibercept 2 mg arms with no retinal vasculitis reported². 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)². The majority of these events were manageable and resolved with routine clinical care².

In KESTREL, the percentage of patients who experienced ≥15 letter loss from baseline at year one was 1.6% for brolucizumab 3 mg, 0% for Beovu 6 mg and 0.5% for aflibercept². In KITE, the percentage of patients who experienced ≥15 letter loss from baseline at year one was 1.1% for Beovu 6 mg and 1.7% for aflibercept². Brolucizumab 6 mg is the commercialized dose of Beovu³.

Regulatory applications for Beovu in DME are under review by the US Food and Drug Administration (FDA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). Discussions with additional health authorities regarding Beovu are ongoing.

*Aflibercept dosing was aligned to the approved EU label in year one of treatment.

More reading

Beovu AMD therapy now listed on the PBS

Novartis AMD drug Beovu secures European approval

Lucentis now TGA-approved for retinopathy of prematurity

References

1. Romero-Aroca P. Managing diabetic macular edema: The leading cause of diabetes blindness. World J Diabetes. 2011;2(6):98-104.
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 (ARVO) 2021 Annual Meeting. May 2021.
3. Beovu [summary of product characteristics] Basel, Switzerland. Novartis: 2020.
4. Eylea [summary of product characteristics] Berlin, Germany. Bayer AG: 2014.
5. Data on file. KESTREL clinical trial protocol (CRTH258B2301). Novartis, 2021.
6. Data on file. KITE clinical trial protocol (CRTH258B2302). Novartis, 2021.
7. National Eye Institute. Macular Edema. Available at: https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/macular-edema. Accessed March 2022.
8. National Eye Institute. Diabetic Retinopathy. Available at: https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/diabetic-retinopathy. Accessed March 2022.
9. Beovu [US prescribing information] East Hanover, NJ. Novartis: 2020.
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11. 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 March 2022.
12. Beovu [prescription medicine decision summary] Australia. Novartis: 2020.