Novartis has terminated the Merlin, Raptor and Raven studies, which were assessing the efficacy and safety of brolucizumab (Beovu) with six initial monthly injections in retinal vein occlusion. The company cited patient safety as the primary reason.
Novartis reported the first interpretable year one results of the Phase III MERLIN study, a two-year study initiated in the second half of 2018, assessing the efficacy and safety of Beovu (brolucizumab) 6mg versus aflibercept 2mg given every four weeks following the loading phase in patients with wet age-related macular degeneration (AMD) who have persistent retinal fluid despite anti-VEGF therapy.
Beovu met MERLIN’s primary endpoint of non-inferiority in change in best corrected visual acuity from baseline and superiority on select anatomical secondary endpoints at year one versus aflibercept, when given every four weeks following the loading phase.1 However, given every four weeks in MERLIN, idiopathic orbital inflammation (IOI) including RV, and RO were reported with a higher frequency in the Beovu 6mg every four weeks arm when compared to aflibercept 2mg every four 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
“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,” said John Tsai, MD, Global Head of Drug Development and Chief Medical Officer, Novartis. “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 four week dosing intervals after the loading phase. In the interest of patient safety, Novartis has 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 four 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 6mg at intervals less than two 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.
When used on a two- to three-month interval following the loading phase, Beovu continues to be an important and effective treatment option for appropriate patients with wet AMD.2,3 Novartis remains committed to supporting the retina community with information regarding Beovu. 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.
References
- Data on file. MERLIN First interpretable results. Novartis; 2021.
- 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.
- 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.
- Beovu [US prescribing information] East Hanover, NJ. Novartis: 2020.
