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38248111000001108

New Medicines

Information

Beovu
New molecular entity
Novartis
Novartis

Development and Regulatory status

Launched
Launched
Launched
April 2020
Apr 20Available in the UK. Beovu 120mg/ml solution for injection in pre-filled syringe, 1=£816.00 [19].
Feb 20Safety concerns about retinal vasculitis may limit initial uptake of brolucizumab [18].
Feb 20Approved in EU [17].
Dec 19Recommended for EU approval by CHMP - the full indication is "the treatment of neovascular (wet) age-related macular degeneration (AMD)." It is proposed that the medicine be prescribed by physicians experienced in administering intravitreal injections for the treatment of neovascular (wet) age-related macular degeneration (AMD)[16].
Oct 19Launched in the US under the brand name Beovu [14].
Oct 19Approved by US FDA for treatment of wet AMD.[13]
Apr 19Filed in US [12].
Mar 19EU Marketing Authorisation Application validated by EMA [11].
Dec 18Filings will now be 2019 for wet AMD [10].
Feb 18Filings now planned for Q4 2018 [8].
Jun 17Filings now planned for 2017. US launch could be 2019 [6].
Dec 16Filings expected to happen in 2018 [4].
Dec 15Filings planned for 2018 or later [3].

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].
Age-related macular degeneration (AMD) - neovascular (wet)
Intravitreal

Further information

Yes
February 2021

Trial or other data

Feb 20The American Society of Retina Specialists (ASRS) has issued a note to members about 14 cases of retinal vasculitis for Beovu patients, 11 of which were occlusive retinal vasculitis that can lead to vision loss. Novartis has engaged an external safety review committee to further evaluate these post-marketing cases [18].
Sep 19PIII randomised, double-blind TALON trial (CRTH258A2303; EudraCT2019-000716-28; NCT04005352) initiated to compare the efficacy and safety of brolucizumab 6 mg to aflibercept 2 mg in a treat-to-control regimen in patients with neovascular AMD. Primary outcome measures are average change in BCVA at weeks 28 and 32, and distribution of the last interval with no disease activity up to week 32. Intended enrolment is 692 patients in Europe (not UK) and estimated primary completion date is Aug 2022 [14,15].
Oct 18Data 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].
Oct 18PIII randomised, double-blind MERLIN trial initiated to compare safety and efficacy of brolucizumab 6mg dosed every 4 weeks to aflibercept 2mg dosed every 4 weeks in patients with wet-age related macular degeneration, who have retinal fluid despite frequent anti-VEGF injections (CRTH258AUS04; NCT03710564). Primary endpoint will be change from baseline in Best-Corrected Visual Acuity (BCVA) at week 52 and intended enrolment is 500 patients in the US. Estimated primary completion date is Jun 2020 [14,15].
Feb 1824-week extension study (n=150) planned for subjects completing the HAWK trial (NCT03386474) [8].
Feb 18HAWK = NCT02307682; HARRIER = NCT02434328.
Jun 17Novartis 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 14A second PIII study of similar design will recruit patients predominantly from Europe, including the UK (NCT02434328) [5].
Dec 14PIII 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

BeovuDiabetic macular oedema

Information

Beovu
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 macular oedema
Intravitreal

Further information

Yes
To be confirmed

Evidence based evaluations

BeovuCentral and branch retinal vein occlusion

Information

Beovu
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). Given every 4 weeks for a total of 6 injections, followed by 48 weeks of individual flexible treatment.
Central retinal vein occlusion has an estimated incidence of around 1 in 100,000 per year. The majority of patients are aged >60 years. Younger patients usually have valvular heart disease. Men are slightly more affected than women [1].
Central and branch retinal vein occlusion
Intravitreal

BeovuProliferative diabetic retinopathy

Information

Beovu
Licence extension / variation
Novartis
Novartis

Development and Regulatory status

None
None
Phase III Clinical Trials

Category

A humanised monoclonal single chain FV antibody fragment inhibiting vascular endothelial growth factor A (VEGF-A). Given every 6 weeks for a total of 3 injections, followed by 12-weekly maintenance.
DR is a chronic progressive, potentially sight-threatening disease of the retinal microvasculature, associated with the prolonged hyperglycaemia of diabetes mellitus and with other DM-linked conditions, such as hypertension. In T1DM, proliferative retinopathy (formation of new vessels) appears after 10 years and affects ~40% after 20 years. In T2DM, these changes may be found at diagnosis because subclinical hyperglycaemia may have been present for a prolonged period. 83% progress to DR [1].
Proliferative diabetic retinopathy
Intravitreal