Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Brolucizumab · 10 trials · 5 indications
BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts
Number of subjects in every 4 weeks (q4w), every 8 weeks (q8w), every 12 weeks (q12w) and every 20 weeks (q20w) intervals at last interval with no disease activity up to Week 56. Last interval with no disease activity (number of weeks): Number of subjects at 20/16/12/8/4-weeks intervals up to Week 56 for the study eye in the extension study
Best-Corrected Visual Acuity (BCVA) was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual Function of the study eye was assessed using the ETDRS protocol. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. The average change in BCVA from Baseline of the extension study at Week 52 and Week 56 was estimated by an analysis of variance (ANOVA) with baseline age categories, baseline BCVA categories and treatment arm in the core study included as fixed effects. Last observation carried forward (LOCF) was used to impute missing BCVA values.
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of \>= 34 ETDRS letters (Snellen equivalent 20/200) at Screening / Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.
No disease activity is defined as no change in visual acuity and no change in other signs of the disease (e.g. Intraretinal Fluid (IRF), Subretinal Fluid (SRF), hemorrhage, leakage, etc.). Treatment interval distribution. Number (%) of subjects at 12/8/4-weeks intervals up to Week 32 for the study eye. If the study treatment is discontinued before Week 16, then the treatment interval is 4 weeks; otherwise. the last interval with no disease activity is used (if there was disease activity, the last interval is shortened by 4 weeks, down to a minimum of 4 weeks). If the duration of the last interval falls within the following ranges of (4-week, 8-week) or (8-week, 12-week) or ≥12-week then the floor value of these ranges was used.
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. Least squares mean estimate - for weeks 28 and 32 combined.
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual Function of the study eye was assessed using the ETDRS protocol. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual Function of the study eye was assessed using the ETDRS protocol. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 73 to 23 (per the inclusion criteria) (approximate Snellen equivalent of 20/40 to 20/320) in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.
Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The overall BCVA score (number of letters read correctly by the patient) was calculated using the BCVA worksheet 0-100 letter score, with higher score indicating improvement in acuity. A positive change from baseline is a favorable outcome. BCVA assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.
Number of participants with ocular and non-ocular treatment emergent events with the new formulation brolucizumab 6 mg in this extension trial up to week 24 vs. the corresponding last 6 months of brolucizumab treatment in the Core trial \>= 2%. Safety assessment of the new formulation brolucizumab 6 mg was based on a within-patient comparison with the last 6 months of corresponding Core safety data. Missing brolucizumab data were imputed using last observation carried forward (LOCF).
| Arm | Type | Description |
|---|---|---|
| Personalized regimen arm | EXPERIMENTAL | 1\~3 x 4-week loading injections and one 8-week injection, followed by Treat-and-extend (T\&E) regimen up to Week 56 |
| Standard regimen arm | ACTIVE_COMPARATOR | 3 x 4-week loading injections and disease activity assessment at week 16 followed by q12w/q8w up to Week 56 |
| brolucizumab 6 mg | EXPERIMENTAL | Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity. |
| Panretinal photocoagulation laser Arm | ACTIVE_COMPARATOR | Initial treatment in 1-4 sessions up to Week 12, followed with additional PRP treatment as needed |
| Aflibercept 2 mg | ACTIVE_COMPARATOR | 3 monthly intravitreal injections of aflibercept 2 mg in the loading treatment period (q4w regimen) up to Week 8 followed by injections every 8 weeks (q8w) up to Week 40. |
| Brolucizumab 6mg q4w | EXPERIMENTAL | Brolucizumab 6 mg/0.05 mL every 4 weeks. |
| Aflibercept 2mg q4w | ACTIVE_COMPARATOR | Aflibercept 2mg/0.05 mL every 4 weeks |
| Brolucizumab 3 mg | EXPERIMENTAL | Brolucizumab 3 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule. To fulfil the double-masking requirement, each investigational site had masked and unmasked staff. The investigator who performed the injection was unmasked to the treatments as were any other site personnel who had been delegated responsibility for working with the Investigational Product (IP). |
| Brolucizumab | EXPERIMENTAL | Brolucizumab 6 mg solution for IVT injection, single injection at Day 1 (baseline), Week 8, and Week 16 or Week 20 |
| Aflibercept | OTHER | Aflibercept 2 mg solution for IVT injection, single injection at Day 1 (baseline), Week 8 and Week 16 to maintain the masking of the extension trial only. |
| Name | Type | Description |
|---|---|---|
| Brolucizumab 6mg | DRUG | Brolucizumab 6mg (intravitreal) Personalized regimen arm: 1\~3 x 4-week loading injections and one 8-week injection, followed by Treat-and-extend (T\&E) regimen up to Week 56 |
| brolucizumab | DRUG | brolucizumab 6 mg/0.05 mL solution for intravitreal injection |
| Brolucizumab 6 mg | BIOLOGICAL | 3 x q6w loading injections, followed by q12w maintenance through Week 90 |
| Panretinal photocoagulation laser | PROCEDURE | initial treatment in 1-4 sessions up to Week 12, followed with additional PRP treatment as needed |
| Aflibercept 2 mg | DRUG | Intravitreal injection |
| Aflibercept | DRUG | 5 x every 4 weeks loading then every 8 weeks maintenance |
Inclusion Criteria: 1. Signed informed consent must be obtained prior to participation in the study. 2. Participants ≥ 50 years of age at Screening. Study eye: 3. Presence of active polypoidal lesions in the macula as shown by Indocyanine green angiography (ICGA) AND presence of serosanguinous ...
Brolucizumab is an investigational monoclonal antibody being developed for ophthalmology indications including age-related macular degeneration, diabetic macular edema, macular polypoidal choroidal vasculopathy, neovascular age-related macular degeneration, and proliferative diabetic retinopathy. It is administered as an intravitreal injection and is currently in Phase 3 clinical development.
Brolucizumab is a humanized single-chain antibody fragment that targets vascular endothelial growth factor A (VEGF-A). By binding to VEGF-A, it inhibits the growth of abnormal blood vessels in the retina, which is the underlying cause of vision loss in conditions like wet age-related macular degeneration and diabetic macular edema.
Brolucizumab is developed by Novartis AG, a multinational pharmaceutical company listed on the New York Stock Exchange under the ticker symbol NVS. Novartis is conducting Phase 3 clinical trials to evaluate the safety and efficacy of brolucizumab across multiple retinal diseases.
Brolucizumab is in Phase 3 clinical development. It is an investigational drug and has not yet been approved by regulatory authorities. Four Phase 3 trials have been completed, evaluating its efficacy and safety compared to standard treatments like aflibercept and panretinal photocoagulation laser.
Brolucizumab has completed four Phase 3 trials. NCT03481660 compared brolucizumab to aflibercept in 360 patients with diabetic macular edema. NCT04005352 (TALON) compared brolucizumab 6mg to aflibercept 2mg in 734 patients with age-related macular degeneration. NCT04058067 compared brolucizumab to aflibercept in 266 Chinese patients with diabetic macular edema. NCT04278417 compared brolucizumab to panretinal photocoagulation laser in 689 patients with proliferative diabetic retinopathy.
Brolucizumab is the international nonproprietary name for the drug marketed under the brand name Beovu. Both names refer to the same anti-VEGF agent developed by Novartis for the treatment of retinal diseases. In clinical trials and regulatory documents, it is referred to as brolucizumab, while Beovu is the commercial brand name.