Novartis announced on March 31st that brolucizumab (Beovu) 6mg has been approved by the European Commission (EC) for the treatment of diabetic macular edema (DME). This drug was first approved by the EC for the treatment of wet age-related macular degeneration (AMD) in 2020 and has now been approved for DME treatment based on the one-year data from the Phase III of the KESTREL and KITE clinical trials. These trials met their primary goal of non-inferior results in terms of best-corrected visual acuity (BCVA) from baseline compared to aflibercept 2mg at the one-year mark. Furthermore, fewer patients treated with Beovu presented intraretinal and subretinal fluid compared to patients administered aflibercept, thus showing potential improvement in fluid resolution.
The current EC-approved prescribing information for Beovu consists of a loading phase of 5 doses that are injected six weeks apart; treatment can then be customized according to the patient’s needs and disease activity. Physicians should consider 12-week intervals between treatments for patients without disease activity, whereas, in patients with disease activity, the gaps should be shortened to 8 weeks. Novartis has submitted regulatory applications for Beovu use in the treatment of DME to the U.S. Food and Drug Administration (FDA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA), which are currently under review.
A little more about the KESTREL and KITE clinical trials
KESTREL and KITE were the first pivotal trials to study anti-vascular endothelial growth factor (VEGF) treatment with a loading phase administration interval of 6-weeks, suggesting that Beovu could offer fewer injections from the start of therapy. They are randomly assigned, double-masked, global, two-year studies that compared the safety and efficacy of Beovu with aflibercept in the treatment of DME in 926 patients from 36 countries.
In the KESTREL arm, patients were divided in a 1:1:1 ratio: brolucizumab 3mg, brolucizumab 6mg or aflibercept 2mg. In the KITE arm, patients were randomly divided in a 1:1 ratio: brolucizumab 6mg or aflibercept 2mg. The loading phase consisted of 5 doses spaced out by 6-weeks in the Beovu arms and by four weeks in the aflibercept arm in both trials. Following the loading phase, Beovu patients were treated every 12 weeks if they did not show any disease activity and every eight weeks if disease activity was noted; as for the aflibercept arm, all patients were treated every eight weeks after the loading phase.
In the KESTREL arm, the percentage of participants that suffered a ≥15 letter loss from baseline at the one-year mark was 1.6% with Beovu 3mg, 0% for Beovu 6mg and 0.5% for aflibercept. In KITE, the same analysis was performed, and the results were 1.1% for Beovu 6mg and 1.7% for aflibercept. The most common (≥5%) adverse events were conjunctival hemorrhage, nasopharyngitis, and hypertension.