Brolucizumab

Unassigned

New Medicines

Neovascular (wet) age-related macular degeneration (AMD)

Information

New molecular entity
Novartis
Novartis

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Pre-registration (Filed)

Apr 19: Filed in US [12].


Mar 19: EU Marketing Authorisation Application validated by EMA [11].

Category

A humanised monoclonal single chain FV antibody fragment targeting vascular endothelial growth factor (VEGF). It inhibits VEGF-A.
The incidence of wet AMD, in people aged 50 and over, is estimated to be around 0.11%; this equates to approximately 39 cases per 100,000 population [1].
Neovascular (wet) age-related macular degeneration (AMD)
Intravitreal

Further information

Yes
To be confirmed

Trial or other data

Oct 18: Data from PIII HAWK and HARRIER studies presented at the American Academy of Ophthalmology 2018 Annual Meeting. Brolucizumab met its primary endpoint of non-inferiority vs. aflibercept in best-corrected visual acuity (BCVA). The mean change in BCVA was 5.9 letters for brolucizumab vs. 5.3 letters for aflibercept in HAWK, and 6.1 letters vs. 6.6 letters in HARRIER. Also, fewer pts with nAMD who were treated with brolucizumab 6mg had intra-retinal fluid (IRF) and/or sub-retinal fluid vs. pts who were treated with aflibercept at 96 weeks [24% for brolucizumab 6mg vs. 37% for aflibercept in HAWK (P=0.0001); 24% vs. 39%, respectively, in HARRIER (P<0.0001)]. Absolute reductions in central subfield thickness (CST) at 96 weeks were ‘175µm for brolucizumab vs. ‘149 µm for aflibercept in HAWK (P=0.0057) and ‘198µm vs.‘155 µm in HARRIER (P<0.0001). Of pts on brolucizumab 6mg who successfully completed year 1 on a 12-week dosing interval, 82% in HAWK and 75% in HARRIER were maintained on a 12-week dosing interval in year 2. No new, previously unreported types of safety events were identified at week 96, and brolucizumab continued to be comparable to aflibercept with the overall incidence of adverse events. The most frequent ocular adverse events were reduced visual acuity, conjunctival hemorrhage, vitreous floaters, eye pain, dry eye, retinal hemorrhage, cataract and vitreous detachment.[9]


Feb 18: 24-week extension study (n=150) planned for subjects completing the HAWK trial (NCT03386474) [8].


HAWK = NCT02307682; HARRIER = NCT02434328.


Jun 17: Novartis announces data from two PIII trials—HARRIER and HAWK—showing that long-acting VEGF brolucizumab matches Eylea when dosed just four times a year. Brolucizumab (at 6-mg and 3-mg doses) matched Eylea (2-mg) in the average change in best-corrected visual acuity (BCVA) over 48 weeks, and the two drugs had comparable side-effect profiles. More than half of the patients in HAWK and HARRIER (57% and 52% respectively) received brolucizumab every 12 weeks [6].


Dec 14: a second PIII study of similar design will recruit patients predominantly from Europe, including the UK (NCT02434328) [5].


Dec 14: PIII study (NCT02307682) to compare RTH258 ophthalmic solution for intravitreal (IVT) injection at two dosage levels to aflibercept solution for IVT injection (2 mg) in subjects with untreated active choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) in the study eye begins. This study will be conducted in Argentina, Australia, Brazil, Canada, Chile, Colombia, Costa Rica, Guatemala, Israel, Japan, Mexico, Panama, Peru, New Zealand, and US (including Puerto Rico) & will recruit 1,600 adults aged 50 years or over. Primary outcome is change in best corrected visual acuity (BCVA) from baseline at week 48. Collection of these data should complete Jun 17[2].


Evidence based evaluations

Diabetic macula oedema

Information

Licence extension / variation
Novartis
Novartis

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

A humanised monoclonal single chain FV antibody fragment inhibiting vascular endothelial growth factor A (VEGF-A). Dosed four times a year.
In 2017-18 there were 3,196,124 registrations of diabetes mellitus in patients aged 17 years and older in England [1]. It is estimated that approximately 7% of people with diabetes have DMO which is about 223,729 of whom 87,254 (39%) have clinically significant macular oedema [2].
Diabetic macula oedema
Intravitreal