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Drug Design, Development and Therapy 2023Degenerative eye conditions such as age-related macular degeneration (AMD), diabetic retinopathy, and retinal vein occlusion are major contributors to significant vision... (Review)
Review
Degenerative eye conditions such as age-related macular degeneration (AMD), diabetic retinopathy, and retinal vein occlusion are major contributors to significant vision loss in developed nations. The primary therapeutic approach for managing complications linked to these diseases involves the intravitreal delivery of anti-vascular endothelial growth factor (VEGF) treatments. Faricimab is a novel, humanised, bispecific antibody that simultaneously binds all VEGF-A isoforms and Angiopoietin-2, which has been approved by regulatory agencies, such as the US Food and Drug Administration (FDA), the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA), for the treatment of neovascular AMD and diabetic macular oedema (DMO). Intravitreal faricimab holds the promise of reducing the treatment burden for patients with these conditions by achieving comparable or superior therapeutic outcomes with fewer clinic visits. The scope of faricimab's application includes addressing complex macular conditions such as DMO. This review intends to elucidate the distinctive pharmacological characteristics of faricimab and provide an overview of the key clinical trials and real-world studies that assess its effectiveness and safety in treating degenerative macular diseases.
Topics: Humans; Vascular Endothelial Growth Factor A; Ranibizumab; Angiogenesis Inhibitors; Bevacizumab; Receptors, Vascular Endothelial Growth Factor; Visual Acuity; Wet Macular Degeneration; Macular Edema; Diabetic Retinopathy; Intravitreal Injections
PubMed: 37746113
DOI: 10.2147/DDDT.S427416 -
JAMA Ophthalmology Jul 2023Aflibercept biosimilars can expand available treatment options in retinal diseases and have the potential to improve patient access to safe and effective therapy. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Aflibercept biosimilars can expand available treatment options in retinal diseases and have the potential to improve patient access to safe and effective therapy.
OBJECTIVE
To establish equivalence in efficacy and similarity in safety, pharmacokinetics, and immunogenicity of SB15 and reference aflibercept (AFL) in neovascular age-related macular degeneration (nAMD).
DESIGN, SETTING, AND PARTICIPANTS
This was a randomized double-masked parallel group phase 3 trial conducted at 56 centers in 10 countries from June 2020 to March 2022, including follow-up through 56 weeks. Of 549 screened participants, 449 participants 50 years and older with treatment-naive nAMD were included and randomly assigned to SB15 (n = 224) or AFL (n = 225). Key exclusion criteria included considerable scarring, fibrosis, atrophy, and hemorrhage. This report includes results up to the end of the parallel group period at week 32. Of the 449 randomized participants, 438 (97.6%) completed week 32 follow-up.
INTERVENTION
Participants were randomized 1:1 to receive 2 mg of SB15 or AFL every 4 weeks for the first 12 weeks (3 injections), followed by dosing every 8 weeks up to week 48, with final assessments at week 56.
MAIN OUTCOMES AND MEASURES
The primary end point was the change in best-corrected visual acuity (BCVA) from baseline to week 8 with predefined equivalence margins of -3 letters to 3 letters. Other key end points were changes in BCVA and central subfield thickness up to week 32, safety, pharmacokinetics, and immunogenicity.
RESULTS
The mean (SD) age among the 449 included participants was 74.0 (8.1) years, and 250 participants (55.7%) were female. Baseline demographic characteristics and most disease characteristics were comparable between treatment groups. The least squares mean change in BCVA from baseline to week 8 in the SB15 group was equivalent to that in the AFL group (6.7 letters vs 6.6 letters, respectively; difference, 0.1 letters; 95% CI, -1.3 to 1.4). Comparable efficacy between treatment groups was maintained up to week 32 (least squares mean change from baseline in BCVA: SB15, 7.6 letters vs AFL, 6.5 letters; least squares mean change from baseline in central subfield thickness: SB15, -110.4 μm vs AFL, -115.7 μm). No clinically relevant differences were observed in the incidence of treatment-emergent adverse events (TEAEs) (SB15, 107/224 [47.8%] vs AFL, 98/224 [43.8%]) and ocular TEAEs in the study eye (SB15, 41/224 [18.3%] vs AFL, 28/224 [12.5%]). The serum concentration profiles and cumulative incidences of overall antidrug antibody positive participants were comparable.
CONCLUSIONS AND RELEVANCE
In this phase 3 randomized clinical trial, SB15 and AFL showed equivalent efficacy and comparable safety, pharmacokinetics, and immunogenicity in participants with nAMD.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04450329.
Topics: Humans; Female; Aged; Male; Angiogenesis Inhibitors; Biosimilar Pharmaceuticals; Treatment Outcome; Visual Acuity; Intravitreal Injections; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Macular Degeneration; Wet Macular Degeneration; Ranibizumab
PubMed: 37289448
DOI: 10.1001/jamaophthalmol.2023.2260 -
Advances in Therapy Dec 2023A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy, durability and safety of faricimab, used in a... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy, durability and safety of faricimab, used in a Treat & Extend (T&E) regime with intervals up to every 16 weeks (Q16W), relative to other therapies currently in use for treatment of diabetic macular oedema (DME). Of particular interest were anti-vascular endothelial growth factor (VEGF) therapies applied in flexible dosing regimens such as Pro re nata (PRN) and T&E, which are the mainstay in clinical practice.
METHODS
An SLR identifying randomised controlled trials (RCTs) published before August 2021 was conducted, followed by a Bayesian NMA comparing faricimab T&E treatment to aflibercept, ranibizumab, bevacizumab, dexamethasone and laser therapy. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA), change in central subfield thickness (CST), injection frequency, ocular adverse events (AE) and all-cause discontinuation, all of which were evaluated at 12 months. Subgroup analyses including patients' naïve to anti-VEGF were conducted where feasible.
RESULTS
Twenty-six studies identified in the SLR were included in the NMA. Most importantly for decision making in clinical practise, faricimab T&E was associated with a statistically greater (95% credible intervals exclude zero) and clinically meaningful decrease in retinal thickness compared to all other flexible dosing regimens (greater retinal drying by 55-125 microns). Anatomical outcomes determine treatment efficacy and retreatment of patients. The NMA also showed a statistically greater increase in mean change in BCVA for faricimab T&E vs. flexible regimens using ranibizumab and bevacizumab (increase of 4.4-4.8 letters) as well as a numerical improvement vs. aflibercept PRN (two letters, 95% credible intervals including zero). Accordingly, the injection frequency was numerically lower versus other treatments using flexible dosing regimens (decrease by 0.92-1.43 injections). The analyses also indicated that the safety profile of faricimab T&E was comparable to those of ranibizumab and aflibercept, which have well-established safety profiles, with similar results for the number of all-cause discontinuations.
CONCLUSION
Faricimab provides a new treatment option in DME with dual-pathway inhibition of VEGF and angiopoeitin-2 (Ang-2). To the authors' knowledge, this is the first indirect comparison of faricimab T&E in DME. The analyses indicate that faricimab T&E is associated with superior retinal drying along with numerically fewer injections compared to all other treatments given in flexible dosing regimens. It also showed superior visual acuity outcomes compared to ranibizumab and bevacizumab.
Topics: Humans; Angiogenesis Inhibitors; Bevacizumab; Diabetic Retinopathy; Intravitreal Injections; Macular Edema; Network Meta-Analysis; Ranibizumab; Vascular Endothelial Growth Factor A
PubMed: 37751021
DOI: 10.1007/s12325-023-02675-y -
Review of real-world evidence of dual inhibition of VEGF-A and ANG-2 with faricimab in NAMD and DME.International Journal of Retina and... Jan 2024Management of vitreoretinal disorders (e.g., neovascular age-related macular degeneration [nAMD] and diabetic macular edema [DME]) have assumed the standard therapy of... (Review)
Review
Management of vitreoretinal disorders (e.g., neovascular age-related macular degeneration [nAMD] and diabetic macular edema [DME]) have assumed the standard therapy of lifelong anti-VEGF injections with drugs like aflibercept, brolucizumab, ranibizumab and bevacizumab. However, the burden imposed on patients is a major deterrent for continual therapy and recovery. Faricimab, a bispecific antibody, blocking both VEGF-A and Ang-2 molecules, produces a comparable functional and anatomical results, with less injections, significantly reducing patient burden. Visual acuity, safety, adverse effects, and anatomical outcomes are discussed in the pivotal clinical trials (YOSEMITE/RHINE and TENAYA/LUCERNE), and early data from real-world studies (TRUCKEE, TAHOE, FARWIDE-DME, FARETINA and others). In YOSEMITE and RHINE, faricimab demonstrated non-inferior vision gains, better anatomical outcomes compared to aflibercept every 8 weeks. Faricimab in the personalized treatment interval (PTI), after week 96, achieved 12-week interval in 78.1% of the patients and 16-week interval in 62.3%. TENAYA and LUCERNE reported comparable best corrected visual acuity (BCVA) improvement and better anatomic outcomes during head-to-head phase, parallel to aflibercept, at its 8-week treatment schedule. Faricimab in the PTI regimen, after week 96 achieved 12-week interval in 77.8% of the patients and 16-week interval in 63.1%. Safety of faricimab has been comparable to aflibercept in these pivotal trials. Real-world data supports the data from the pivotal studies regarding the efficacy and safety profile of faricimab in heterogenous real world patient population. Moreover, in previously treated patients, it also demonstrated a faster fluid resolution, good safety profile. Considering faricimab has demonstrated anatomic and durability benefit in the treatment of nAMD and DME, additional data from ongoing extension clinical trials, AVONELLE-X and RHONE-X will help understand longer term outcomes for patients treated with faricimab as well as patients switching from aflibercept to faricimab after finishing the pivotal trials. Longer term data from the real-world studies will also continue to contribute to our understanding of long-term efficacy, safety and durability in the real world patient population.
PubMed: 38233896
DOI: 10.1186/s40942-024-00525-9 -
Ophthalmology Sep 2023To compare the efficacy and the safety of submacular hemorrhage (SMH) management using either surgical pars plana vitrectomy (PPV) or pneumatic displacement (PD) with... (Randomized Controlled Trial)
Randomized Controlled Trial
Surgery, Tissue Plasminogen Activator, Antiangiogenic Agents, and Age-Related Macular Degeneration Study: A Randomized Controlled Trial for Submacular Hemorrhage Secondary to Age-Related Macular Degeneration.
PURPOSE
To compare the efficacy and the safety of submacular hemorrhage (SMH) management using either surgical pars plana vitrectomy (PPV) or pneumatic displacement (PD) with tissue plasminogen activator (tPA) and vascular endothelial growth factor (VEGF) inhibitor added to each arm.
DESIGN
Randomized, open-label, multicenter superiority study.
PARTICIPANTS
Ninety patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older with recent SMH (≤ 14 days) of more than 2 optic disc areas and predominantly overlying the retinal pigment epithelium.
METHODS
Patients were assigned randomly to surgery (PPV, subretinal tPA [maximum, 0.5 ml/50 μg], and 20% sulfur hexafluoride [SF] tamponade) or PD (0.05 ml intravitreal tPA [50 μg] and 0.3 ml intravitreal pure SF). Both groups were asked to maintain a head upright position with the face forward at 45° for 3 days after intervention and received 0.5 mg intravitreal ranibizumab at the end of the intervention, at months 1 and 2, as the loading phase, and then on a pro re nata regimen during a 6-month follow-up.
MAIN OUTCOME MEASURES
The primary efficacy endpoint was mean best-corrected visual acuity (VA) change at month 3. The secondary endpoints were mean VA change at month 6, 25-item National Eye Institute Visual Function Questionnaire composite score value at months 3 and 6, number of anti-VEGF injections, and complications during the 6-month follow-up.
RESULTS
Of the 90 patients randomized, 78 patients (86.7%) completed the 3-month efficacy endpoint visit. The mean VA change from baseline to month 3 in the surgery group (+16.8 letters [95% confidence interval (CI), 8.7-24.9 letters]) was not significantly superior to that in the PD group (+16.4 letters [95% CI, 7.1-25.7 letters]; adjusted difference β, 1.9 [-11.0; 14.9]; P = 0.767). Both groups achieved similar secondary outcomes at month 6. No unexpected ocular safety concerns were observed in either group.
CONCLUSIONS
Surgery did not yield superior visual gain nor additional benefit for SMH secondary to nAMD compared with PD at 3 months, with intravitreal anti-VEGF added to each arm. Both treatment strategies lead to a clinical improvement of VA without safety concerns for SMH over 6 months. Both design and results of the trial cannot be used to establish equivalence between treatments.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Middle Aged; Infant, Newborn; Tissue Plasminogen Activator; Angiogenesis Inhibitors; Fibrinolytic Agents; Vascular Endothelial Growth Factor A; Ranibizumab; Retinal Hemorrhage; Macular Degeneration; Retinal Pigment Epithelium; Intravitreal Injections
PubMed: 37088447
DOI: 10.1016/j.ophtha.2023.04.014 -
Frontiers in Pediatrics 2023Anti-VEGF drugs like ranibizumab can be used to treat retinopathy of prematurity (ROP) by halting the formation of abnormal blood vessels, or lasers can be used to burn... (Review)
Review
UNLABELLED
Anti-VEGF drugs like ranibizumab can be used to treat retinopathy of prematurity (ROP) by halting the formation of abnormal blood vessels, or lasers can be used to burn the edges of the retina where these vessels are present. The objective is to compare the efficacy for ROP between ranibizumab and laser therapy.
MATERIAL AND METHODS
Electronic searches will be carried out in medical databases with key words and controlled vocabulary terms. Randomized controlled trials (RCT) will be assessed. The primary outcome will be the full ROP regression. Two reviewers will extract the data using predefined forms and, to assess the quality of the study, we will use RoB 2.0, the tool for randomized controlled trials developed by the Cochrane Collaboration. We used a combination of the inverse-variance approach and random-effects models for the meta-analysis.
RESULTS
The eyes of 182 preterm infants who had ranibizumab treatment were assessed in a total of 364 eyes, and 135 infants received laser therapy. The follow-up period was between 6 and 24 months. Ranibizumab was not associated with greater regression of ROP compared to laser therapy in preterm infants (RR: 1.09, CI 95%: 0.95-1.24; : 0.22). Also, ranibizumab was not associated with recurrence of ROP compared to laser therapy in preterm infants (RR: 3.77, CI 95%: 0.55-25.81; : 0.22).
CONCLUSIONS
The efficacy of ranibizumab compared to laser is very uncertain in terms of ROP regression and decreased ROP recurrence in preterm infants.
SYSTEMATIC REVIEW REGISTRATION
identifier PROSPERO (CRD42022324150).
PubMed: 37601137
DOI: 10.3389/fped.2023.1202927 -
International Journal of Molecular... Aug 2023Neovascular age-related macular degeneration (nAMD) is the primary disastrous retinal disease that leads to blindness in the elderly population. In the early 2000s, nAMD... (Review)
Review
Neovascular age-related macular degeneration (nAMD) is the primary disastrous retinal disease that leads to blindness in the elderly population. In the early 2000s, nAMD resulted in irreversible vision loss and blindness with no available treatment options. However, there have been breakthrough advances in the drug development of anti-angiogenic biological agents over the last two decades. The primary target molecule for treating nAMD is the vascular endothelial growth factor (VEGF), and there are currently several anti-VEGF drugs such as bevacizumab, ranibizumab, and aflibercept, which have made nAMD more manageable than before, thus preventing vision loss. Nevertheless, it should be noted that these anti-VEGF drugs for nAMD treatment are not effective in more than half of the patients, and even those who initially gain visual improvements lose their vision over time, along with potential deterioration in the geography of atrophy. As a result, there have been continuous endeavors to improve anti-VEGF agents through better efficacy, fewer doses, expanded intervals, and additional targets. This review describes past and current anti-VEGF therapeutics used to treat nAMD and outlines future directions to improve the effectiveness and safety of anti-VEGF agents.
Topics: Humans; Aged; Vascular Endothelial Growth Factors; Bevacizumab; Blindness; Angiogenesis Inhibitors; Macular Degeneration
PubMed: 37629185
DOI: 10.3390/ijms241613004 -
Medicine Aug 2023Ranibizumab addition may benefit to improve the efficacy in patients with diabetic retinopathy than only photocoagulation, and this meta-analysis aims to explore the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ranibizumab addition may benefit to improve the efficacy in patients with diabetic retinopathy than only photocoagulation, and this meta-analysis aims to explore the impact of ranibizumab addition on efficacy for diabetic retinopathy.
METHODS
PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched, and we included randomized controlled trials assessing the effect of ranibizumab addition on patients with diabetic retinopathy for this meta-analysis.
RESULTS
Six randomized controlled trials were finally included in the meta-analysis. Overall, compared with control intervention for diabetic retinopathy, ranibizumab addition showed significantly increased number of neovascularization area reduction (OR = 4.20; 95% CI = 1.47-12.02; P = .007) and reduced fluorescein leakage (MD = -2.53; 95% CI = -3.31 to -1.75; P < .00001), but showed no obvious impact on neovascularization area (MD = -1.80; 95% CI = -3.68 to 0.08; P = .06), photocoagulation retreatment (OR = 1.03; 95% CI = 0.47-2.27; P = .94) or adverse events (OR = 1.45; 95% CI = 0.49-4.29; P = .50).
CONCLUSIONS
Ranibizumab combined with photocoagulation is effective to improve efficacy for diabetic retinopathy.
Topics: Humans; Ranibizumab; Diabetic Retinopathy; Angiogenesis Inhibitors; Bevacizumab; Vascular Endothelial Growth Factor A; Laser Coagulation; Intravitreal Injections; Diabetes Mellitus
PubMed: 37543834
DOI: 10.1097/MD.0000000000034170