Faricimab for the Treatment of Diabetic Macular Edema and Neovascular Age-Related Macular Degeneration.
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SUBMITTER: Ferro Desideri L
PROVIDER: S-EPMC10222467 | biostudies-literature | 2023 May
REPOSITORIES: biostudies-literature
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Faricimab for the Treatment of Diabetic Macular Edema and Neovascular Age-Related Macular Degeneration.
Ferro Desideri Lorenzo L Traverso Carlo Enrico CE Nicolò Massimo M Munk Marion R MR
Pharmaceutics 20230505 5
Nowadays; intravitreal anti-vascular endothelial growth factor (VEGF) drugs are considered the first-line therapeutic strategy for treating macular exudative diseases; including wet age-related macular degeneration (w-AMD) and diabetic macular edema (DME). Despite the important clinical achievements obtained by anti-VEGF drugs in the management of w-AMD and DME; some limits still remain; including high treatment burden; the presence of unsatisfactory results in a certain percentage of patients a ...[more]
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Project description:PurposeEvaluate the ocular pharmacodynamics (PD) of intravitreal faricimab, a bispecific inhibitor of angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A), in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME).MethodsAqueous humor (AH) samples (1025 free Ang-2 concentrations and 1345 free VEGF-A concentrations) were collected from approximately 300 faricimab-treated patients with nAMD or DME in phase 2/3 trials. A population pharmacokinetic pharmacodynamic (popPKPD) model was developed to describe the dynamic effect of faricimab on free AH Ang-2 and VEGF-A.ResultsMean baseline Ang-2 concentrations were 8.1 and 13.4 pg/mL in patients with nAMD and DME, respectively. The corresponding mean baseline VEGF-A concentrations were 58 and 135 pg/mL, respectively. Overall, approximately 79% of Ang-2 (84% within 8 weeks postdose and 55% beyond 12 weeks postdose) and 7% of VEGF-A postdose observations were below the lower limit of quantification. Model-derived Ang-2 and VEGF-A concentration-time profiles for patients on every 4-week/every 8-week dosing were predicted to maintain greater than 50% suppression of Ang-2 concentrations for the entire dosing period. Patients on every 12-week/16-week dosing were predicted to have greater than 50% Ang-2 suppression for 12 or more weeks, whereas 50% VEGF-A suppression was maintained for 9 to 10 weeks. At 8 weeks postdose, the median Ang-2 concentrations remained suppressed by approximately 80%. At 16 weeks postdose, the median VEGF-A concentrations returned to baseline, but median Ang-2 levels remained below baseline.ConclusionsA popPKPD analysis demonstrated faricimab's rapid and sustained suppression of AH Ang-2 and VEGF-A.Translational relevanceA popPKPD analysis suggested that sustained suppression of ocular Ang-2 contributes to faricimab's extended durability, observed in clinical trials.
| S-EPMC11562974 | biostudies-literature
Project description:IntroductionIntravitreal anti-vascular endothelial growth factor (VEGF) therapy has become the mainstay of treatment in many retinal diseases. The comparative efficacy and safety of newer bispecific anti-VEGF/angiopoietin 2 (Ang2) agents in the treatment paradigm versus widely used monospecific anti-VEGF agents remains unclear.MethodsA systematic literature search of MEDLINE, Embase, and Cochrane Library was conducted to identify comparative observational studies and randomized controlled trials published from 2015 to Jul 2024. With assessment by three independent reviewers, original English peer-reviewed full-text articles evaluating faricimab versus monospecific anti-VEGF agent(s) in FDA-indicated retinal disease with data on at least one set of efficacy and/or safety outcomes for each treatment arm and a minimum 3-month follow-up period were included. Data were appraised using the Cochrane RoB2 and ROBINS-I tools, PRISMA, and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines. All outcomes were collected at the last follow-up. Random effects meta-analyses with 95% confidence intervals were conducted to calculate weighted mean differences and risk ratios. Change in best-corrected visual acuity (BCVA, ETDRS letters), change in central subfield thickness (CSFT, μm), and presence of retinal fluid were primary endpoints; ocular adverse events were secondary endpoints.ResultsAcross 13 studies, in the context of neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO), 2,226 eyes received anti-VEGF monotherapy and 3,022 received faricimab. Final and change in BCVA were similar between treatment groups. Faricimab was associated with a significantly higher reduction in CSFT in DME and RVO eyes but not in nAMD eyes. The incidence of ocular adverse events was similar between groups.ConclusionThere was no difference in BCVA between faricimab and anti-VEGF monotherapy in nAMD, DME, and RVO. While faricimab offered superior improvement in CSFT at the final follow-up for DME and RVO eyes, this effect was not seen in nAMD eyes. Future studies are needed to establish the long-term safety and efficacy of faricimab for retinal vascular disease.
| S-EPMC11614417 | biostudies-literature
Project description:Background: Retinal diseases are major contributors to disability, significantly affecting patients' quality of life. Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) represent a significant disease and economic burden in Colombia. Assessing the economic evaluation of available treatments is essential for the efficient allocation of healthcare resources. Objective: To estimate the cost-effectiveness and budget impact of using faricimab for the treatment of patients with DME and nAMD within the Colombian health system. Methods: This study used a 25-year Markov cohort model to estimate the cost-effectiveness of faricimab vs aflibercept, ranibizumab, and brolucizumab. We used the methodological guidelines of the local health technology assessment agency for conducting the cost-effectiveness and budget impact analysis. Transition probabilities and injection frequencies were derived from the literature. Drug prices were retrieved from public local databases. Quality-adjusted life years (QALYs) were assessed. The potential patient population for the budget impact analysis was estimated based on disease prevalence and expert consultations. Results: Faricimab treat-and-extend (T&E) was dominant vs aflibercept T&E (+0.22 QALYs), ranibizumab T&E (+0.55 QALYs), and brolucizumab for 8 to 12 weeks (+0.06 QALYs) in DME, generating cost savings (in US dollars) of 3849, 1375, and 2824,respectively.InnAMD,faricimabalsoshoweddominancevsafliberceptasneeded(+0.12QALYs),ranibizumabasneeded(+0.05QALYs),andbrolucizumab8to12weeks(+0.12QALYs)withsavingsin(US) 7223, 5792,and 6798, respectively. Assuming an annual market share increase for faricimab of 15% for DME and 13% for nAMD, the Colombian Health System could save 144millionover3years.Ofthesesavings, 122.7 million are attributed to drug costs and 21.3milliontoadministrationcosts(US 1 = Col$4325). Conclusion: Considering a willingness to pay threshold of $5988 per additional QALY, faricimab is a cost-effective alternative for both DME and nAMD for the Colombian healthcare system, showing dominance over other anti-vascular endothelial growth factor agents. Faricimab provides better health outcomes at lower costs vs other treatments.
| S-EPMC11884430 | biostudies-literature
Project description:PurposeTo develop machine learning (ML) models to predict, at baseline, treatment outcomes at month 9 in patients with neovascular age-related macular degeneration (nAMD) receiving faricimab.DesignRetrospective proof of concept study.ParticipantsPatients enrolled in the phase II AVENUE trial (NCT02484690) of faricimab in nAMD.MethodsBaseline characteristics and spectral domain-OCT (SD-OCT) image data from 185 faricimab-treated eyes were split into 80% training and 20% test sets at the patient level. Input variables were baseline age, sex, best-corrected visual acuity (BCVA), central subfield thickness (CST), low luminance deficit, treatment arm, and SD-OCT images. A regression problem (BCVA) and a binary classification problem (reduction of CST by 35%) were considered. Overall, 10 models were developed and tested for each problem. Benchmark classical ML models (linear, random forest, extreme gradient boosting) were trained on baseline characteristics; benchmark deep neural networks (DNNs) were trained on baseline SD-OCT B-scans. Baseline characteristics and SD-OCT data were merged using 2 approaches: model stacking (using DNN prediction as an input feature for classical ML models) and model averaging (which averaged predictions from the DNN using SD-OCT volume and from classical ML models using baseline characteristics).Main outcome measuresTreatment outcomes were defined by 2 target variables: functional (BCVA letter score) and anatomical (percent decrease in CST from baseline) outcomes at month 9.ResultsThe best-performing BCVA regression model with respect to the test coefficient of determination (R2) was the linear model in the model-stacking approach with R2 of 0.31. The best-performing CST classification model with respect to test area under receiver operating characteristics (AUROC) was the benchmark linear model with AUROC of 0.87. A post hoc analysis showed the baseline BCVA and the baseline CST had the most effect in the all-model prediction for BCVA regression and CST classification, respectively.ConclusionsPromising signals for predicting treatment outcomes from baseline characteristics were detected; however, the predictive benefit of baseline images was unclear in this proof-of-concept study. Further testing and validation with larger, independent datasets is required to fully explore the predictive capacity of ML models using baseline imaging data.Financial disclosuresProprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
| S-EPMC10585644 | biostudies-literature
Project description:PurposeTo describe the rationale and design of the VOYAGER (NCT05476926) study, which aims to investigate the safety and effectiveness of faricimab and the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) in clinical practice. VOYAGER also aims to understand drivers of clinical practice treatment outcomes by gaining novel insight into the intersection of treatment regimens, decisions, anatomic outcomes, and vision.DesignPrimary data collection, noninterventional, prospective, multinational, multicenter clinical practice study.ParticipantsAt least 5000 patients initiating/continuing faricimab or PDS for nAMD/DME (500 sites, 31 countries).MethodsManagement will be per usual care, with no mandated scheduled visits/imaging protocol requirements. Using robust methodologies, relevant clinical and ophthalmic data, including visual acuity (VA), and data on treatment clinical setting/regimens/philosophies, presence of anatomic features, and safety events will be collected. Routinely collected fundus images will be uploaded to the proprietary Imaging Platform for analysis. An innovative investigator interface will graphically display the patient treatment journey with the aim of optimizing treatment decisions.Main outcome measuresPrimary end point: VA change from baseline at 12 months per study cohort (faricimab in nAMD and in DME, PDS in nAMD). Secondary end points: VA change over time and per treatment regimens (fixed, treat-and-extend, pro re nata, and other) and number. Exploratory end points: VA change in relation to presence/location of anatomic features that impact vision (fluid, central subfield thickness, fibrosis, atrophy, subretinal hyperreflective material, diabetic retinopathy severity, and disorganization of retinal inner layers) and per treatment regimen/philosophies. The impact of regional and practice differences on outcomes will be assessed as will safety.ResultsRecruitment commenced in November 2022 and will continue until late 2027, allowing for up to 5 years follow-up. Exploratory interim analyses are planned annually.ConclusionsVOYAGER is an innovative study of retinal diseases that will assess the effectiveness and safety of faricimab and PDS in nAMD and DME and identify clinician- and disease-related factors driving treatment outcomes in clinical practices globally to help optimize vision outcomes.Financial disclosuresProprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
| S-EPMC10831184 | biostudies-literature
Project description:PurposeTo report short-term outcomes of treatment switch to faricimab in real-world patients with aflibercept-resistant neovascular age-related macular degeneration (AMD).MethodsSingle-center, retrospective cohort study with chart-review using electronic injection database, electronic medical records, and optical coherence tomography (OCT) data from May to September 2023.ResultsA total of 50 eyes of 46 patients were analyzed. Faricimab treatment led to absence of fluid in 32% of the eyes and a reduction of fluid in 84% of the eyes. There was a statistically significant decrease in central retinal thickness (CRT) and pigment epithelial detachment (PED) height in those that responded to the switch (median difference: - 31 μm, IQR: 55, p < 0.0001 and median difference: - 21 μm, IQR: 36, p < 0.0001, respectively) and a statistically significant increase in CRT (median difference: + 19 μm, IQR: 20, p = 0.0143) and no change in PED height (median difference: + 22 μm, IQR: 64, p = 0.1508) in those that did not. Best-corrected visual acuity (BCVA) showed marginal decrease with low statistical significance. No ocular or systemic safety events were observed.ConclusionsOur findings suggest that switching to faricimab is generally safe and effective in patients with neovascular AMD who are otherwise difficult to treat and have residual fluid despite frequent injections with aflibercept. We observed a high rate of morphological response to the treatment switch, improvement of anatomical parameters with about one-third of patients having dry macula following a single injection, and a marginal change in BCVA. Sustainability of these results requires further investigation.Study registrationClinicalTrials.gov registration number: NCT06124677. Date of registration: 09/11/2023, retrospectively registered.
| S-EPMC11222265 | biostudies-literature
Project description:BackgroundTo systematically review the real-world outcomes of intravitreal faricimab treatment in patients with neovascular age-related macular degeneration (nAMD) to evaluate its efficacy and safety in clinical settings. This study was conducted due to the need for real-world evidence to complement the findings from controlled clinical phase-III trials.MethodsA systematic literature search was conducted on March 17, 2024, across 11 databases, utilizing search terms specifically tailored each database. All studies were reviewed qualitatively with specific focus on the outcomes of interest: the best-corrected visual acuity (BCVA), the central retina thickness (CRT), and the burden of therapy.ResultsWe identified a total of 22 eligible studies of 1762 eyes from 1618 patients with nAMD. Studies reported that intravitreal faricimab injections maintained BCVA in patients with previously treated eyes and demonstrated statistically significant improvement in patients with treatment-naïve eyes. The CRT was reduced after intravitreal faricimab therapy. Faricimab was well-tolerated, with no significant safety concerns identified, and reduced the overall burden of therapy.ConclusionReal-world studies corroborate the conclusions drawn from phase-III trials regarding faricimab treatment, demonstrating improvement in both visual and anatomical outcomes. Additionally, no significant safety issues were identified, as the treatment was generally well-tolerated and reduced the overall burden of therapy in the real-world settings.
| S-EPMC11245828 | biostudies-literature
Project description:IntroductionNew anti-vascular endothelial growth factor (VEGF) treatments are emerging for the treatment of diabetic macular edema (DME)/neovascular age-related macular degeneration (nAMD). This study aimed to explore the treatment attributes patients find important when deciding on treatment options.MethodsThis noninterventional survey study assessed treatment preferences through a discrete choice experiment (DCE) among patients with DME/nAMD in the USA, Canada, France, Italy, Spain, and the UK. The DCE design was informed by a targeted literature review and qualitative interview research and included five treatment attributes: mode of administration, frequency of examinations, frequency of injections or refills, likely change in visual acuity, and eye-related side effects. Conditional logit models were used to analyze the choice data.ResultsOverall, 537 patients completed the DCE (DME, n = 173; nAMD, n = 364). Patients reported preferring "injection" over "implant surgery and refills" and better visual outcomes over "stabilization," which were also the most important attributes driving preference (35.1% and 31.5%, respectively). They also showed a preference for less-frequent treatment and examinations and for "mild-moderate, frequent" over "severe, rare" side effects. These findings were generally consistent across the two conditions, although significant differences were found depending on anti-VEGF treatment duration (nAMD, DME) and number of reported barriers (nAMD).ConclusionPatient preferences for treatment are driven by several factors. Considering these preferences is essential when designing/introducing new therapies. Individual treatment preferences should be identified and given key consideration when helping patients select from an expanding array of treatment options.
| S-EPMC11844665 | biostudies-literature
Project description:ObjectivesTo investigate the eligibility of a real-world neovascular age-related macular degeneration (nAMD) population for the TENAYA and LUCERNE trials (testing faricimab), and to compare the eligible real-world patients to trial participants.Design, settings and participantsIn this retrospective cross-sectional study, we used data from the Swedish Macula Registry (SMR) between 1 January 2017 and 31 December 2020. Persons were eligible if they fulfilled the main inclusion criteria in TENAYA and LUCERNE: (1) nAMD diagnosis, (2) treatment naïve, (3) ≥50 years and (4) best-corrected visual acuity (BCVA) of 78-24 letters.Main outcome measuresCharacteristics at the original visit of the eligible SMR population and baseline data from the clinical trials were compared.ResultsIn total, 27 962 individuals with nAMD were registered in SMR. A total of 15 399 (55%) individuals were treatment naïve; of these, 15 368 (55%) were ≥50 years and 13 265 (47%) also had BCVA of 78-24 letters and fulfilled eligibility. Among treatment-naïve individuals, 86% were eligible and the BCVA criterion was the most common reason for non-eligibility. The eligible SMR population was significantly older than either TENAYA or LUCERNE. SMR included more women and patients with worse visual acuity than TENAYA, while SMR patients were diagnosed more quickly than LUCERNE.ConclusionsAlmost half of the real-world nAMD population in SMR fulfilled the main inclusion criteria of the TENAYA and LUCERNE trials. Among treatment-naïve individuals, 86% were eligible. Marginally differences were shown between the eligible SMR population and the trial populations. The SMR population were older and more similar to the population in LUCERNE than TENAYA.
| S-EPMC9472139 | biostudies-literature
Project description:We conducted a systematic review and meta-analysis to evaluate the visual, anatomical, and safety outcomes of the intravitreal faricimab, a novel vascular endothelial growth factor (VEGF)/angiopoietin-2 (Ang-2) bispecific agent, in neovascular age-related macular degeneration (nAMD) patients. The follow-up times in the included studies ranged from a minimum of 36 weeks to a maximum of 52 weeks. EMBASE, Ovid-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, the WHO ICTRP, ClinicalTrial.gov, the EU Clinical Trials Register, and Chinese Clinical Trial Registry (ChiCTR) were searched (The last literature search was performed on August 17, 2023) for randomized controlled trials (RCTs) comparing faricimab with control groups for neovascular age-related macular degeneration (nAMD). The risk of bias for eligible RCTs was independently assessed using the Cochrane Risk of Bias Tool by two authors (W.-T.Y. and C.-S.W.). The meta-analysis was conducted using Review Manager 5.4 software. The mean best corrected visual acuity (BCVA), central subfield thickness (CST), total choroidal neovascularization (CNV) area, and total lesion leakage were analyzed as continuous variables and the outcome measurements were reported as the weighted mean difference (WMD) with a 95% confidence interval (CI). The ocular adverse events and ocular serious adverse events were analyzed as dichotomous variables and the outcome measurements were analyzed as the odds ratios (ORs) with a 95% CI. Random-effects model was used in our study for all outcome synthesizing due to different clinical characteristics. Four RCTs with 1,486 patients were eligible for quantitative analysis. There was no statistically significant difference between intravitreal faricimab and anti-VEGF in BCVA [weighted mean difference (WMD) = 0.47; 95% CI: (- 0.17, 1.11)]. The intravitreal faricimab group showed numerically lower CST [WMD = - 5.96; 95% CI = (- 7.11, - 4.82)], total CNV area [WMD = - 0.49; 95% CI = (- 0.68, - 0.30)], and total lesion leakage [WMD = - 0.88; 95% CI = (- 1.08, - 0.69)] after intravitreal therapy compared with the intravitreal anti-VEGF group. There were no statistically significant differences between intravitreal faricimab and anti-VEGF in ocular adverse events (AEs) [pooled odds ratio (OR) = 1.10; 95% CI = (0.81, 1.49)] and serious adverse events (SAEs) [pooled OR = 0.84; 95% CI = (0.37, 1.90)]. The intravitreal bispecific anti-VEGF/angiopoietin 2 (Ang2) antibody faricimab with a extended injection interval was non-inferior to first-line anti-VEGF agents in BCVA. It was safe and had better anatomical recovery. Large, well-designed RCTs are needed to explore the potential benefit of extended faricimab for nAMD. This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022327450).
| S-EPMC10827713 | biostudies-literature