Novartis Terminates Three Trials of Beovu Despite Meeting Primary Endpoint of MERLIN Trial

Novartis reported that Beovu met its primary endpoint in the phase 3 MERLIN trial, but decided to terminate the study due to higher rates of intraocular inflammation with frequent dosing intervals.

Novartis reported the first interpretable year 1 results of the MERLIN trial, a 2-year study initiated in 2018 assessing the efficacy and safety of Beovu (brolucizumab–dbll) 6 mg versus aflibercept 2 mg given every 4 weeks following the loading phasein patients with wet age-related macular degeneration (AMD) who have persistent retinal fluid despite anti-VEGF therapy. Beovu met MERLIN’s primary endpoint of noninferiority in change in best corrected visual acuity from baseline and superiority on select anatomical secondary endpoints at year 1 versus aflibercept when given every 4 weeks following the loading phase.¹ 

However, in the MERLIN trial, intraocular inflammation (IOI), including retinal vasculitis and retinal vein occlusion, were reported with a higher frequency in the Beovu 6 mg every 4 weeks arm when compared to aflibercept 2 mg every 4 weeks (IOI: 9.3% vs 4.5% of which RV: 0.8% vs 0.0%; RO: 2.0% vs 0.0%).¹ The overall rate of vision loss (15 letters or more) due to all causes was 4.8% in the Beovu arm and 1.7% in the aflibercept arm.¹

“Although longer dosing intervals may benefit many people living with wet AMD and other retinal diseases, some are in need of monthly dosing to address persistent fluid. We initiated MERLIN and other clinical programs to explore Beovu for these patients,” John Tsai, MD, Global Head of Drug Development and Chief Medical Officer, Novartis, said in a company news release. “These data help inform our trials moving forward, so we can best determine how appropriate patients can benefit most from this important medicine.”

Novartis evaluated all ongoing brolucizumab clinical programs assessing studies with 4 week dosing intervals after the loading phase. In the interest of patient safety, Novartis decided to terminate the MERLIN study and the RAPTOR and RAVEN studies, which were assessing the efficacy and safety of brolucizumab with six initial monthly injections in retinal vein occlusion. All other relevant ongoing trial protocols will be amended to discontinue 4 week dosing intervals after the loading phase. Clinical trial investigators have been informed and will appropriately follow up with their patients. Physicians should not treat patients with Beovu 6 mg at intervals less than 2 months beyond the first three doses.

Novartis has proactively communicated these data to health authorities and will pursue an update to the Beovu prescribing information globally.

According to Novartis, when used on a 2- to 3-month interval following the loading phase, Beovu continues to be an effective treatment option for appropriate patients with wet AMD. Beovu is contraindicated in patients with ocular or periocular infections, active intraocular inflammation or known hypersensitivity to brolucizumab.⁴

Further analysis of the clinical data from MERLIN is ongoing, and detailed data will be presented at an upcoming medical meeting. 

Reference

1) Data on file. MERLIN First interpretable results. Novartis; 2021.

2) Dugel PU, Koh A, Ogura Y, et al. HAWK and HARRIER: Phase 3, Multicenter, Randomized, Double-Masked Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration. Ophthalmology. 2020;127(1):72-84.

3) Dugel PU, Singh RP, Koh A, et al. HAWK and HARRIER: Ninety-Six-Week Outcomes from the Phase 3 Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration. Ophthalmology. 2021;128(1):89-99.

4) Beovu [US prescribing information] East Hanover, NJ. Novartis: 2020.