Browsing by Subject "Anti-VEGF"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Double-Masked, Randomized, Phase 2 Evaluation of Abicipar Pegol (an Anti-VEGF DARPin Therapeutic) in Neovascular Age-Related Macular Degeneration
    (Mary Ann Liebert, 2018-11-09) Callanan, David; Kunimoto, Derek; Maturi, Raj K.; Patel, Sunil S.; Staurenghi, Giovanni; Wolf, Sebastian; Cheetham, Janet K.; Hohman, Thomas C.; Kim, Kimmie; López, Francisco J.; Schneider, Susan; Ophthalmology, School of Medicine
    PURPOSE: To evaluate safety and efficacy of the vascular endothelial growth factor binding protein abicipar pegol (abicipar) versus ranibizumab for neovascular age-related macular degeneration. METHODS: Phase 2, multicenter, randomized, double-masked comparison (REACH study, stage 3). Patients (n = 64) received intravitreal injections of abicipar 1 mg or 2 mg at baseline, week 4, and week 8 (3 injections) or ranibizumab 0.5 mg at baseline and monthly (5 injections). RESULTS: In the abicipar 1 mg (n = 25), abicipar 2 mg (n = 23), and ranibizumab (n = 16) arms, respectively, least-squares mean best-corrected visual acuity (BCVA) change from baseline was +6.2, +8.3, and +5.6 letters at week 16 (primary endpoint) and +8.2, +10.0, and +5.3 letters at week 20. Least-squares mean central retinal thickness (CRT) reduction from baseline was 134, 113, and 131 μm at week 16 and 116, 103, and 138 μm at week 20. Intraocular inflammation adverse events (AEs), reported in 5/48 (10.4%) abicipar-treated patients, resolved without sustained vision loss or other sequelae. CONCLUSIONS: Abicipar demonstrated durability of effect: BCVA and CRT improvements were similar between abicipar and ranibizumab at weeks 16 and 20 (8 and 12 weeks after the last abicipar injection and 4 weeks after the last ranibizumab injection). No serious AEs were reported.
  • Thumbnail Image
    Item
    Longer-Term Anti-VEGF Therapy Outcomes in Neovascular Age-Related Macular Degeneration, Diabetic Macular Edema, and Vein Occlusion-Related Macular Edema: Clinical Outcomes in 130 247 Eyes
    (Elsevier, 2022-09) Ciulla, Thomas A.; Hussain, Rehan M.; Taraborelli, Donna; Pollack, John S.; Williams, David F.; Ophthalmology, School of Medicine
    Purpose The clinical practice visual acuity (VA) outcomes of anti-VEGF therapy for up to 5 years were assessed in patients with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), branch retinal vein occlusion-related macular edema (BRVO-ME), and central retinal vein occlusion-related macular edema (CRVO-ME). Design A retrospective analysis was performed using the Vestrum Health Retina Database. Participants Treatment-naive patients with nAMD, DME, BRVO-ME, or CRVO-ME who received anti-VEGF injections between 2014 and 2019 and had follow-up data for ≥12 months. Methods Data on age, sex, the number of anti-VEGF treatments, and VA were analyzed. Main Outcome Measures Mean VA change up to 3 years (BRVO-ME and CRVO-ME) and 5 years (nAMD and DME). Results At 1, 3, and 5 years, in 67 666, 21 305, and 5208 eyes with nAMD, after a mean of 7.6, 19.5, and 32 injections, there was a mean change of +3.1, −0.2, and −2.2 letters, respectively. At 1, 3, and 5 years, in 40 832, 7728, and 1192 eyes with DME, after a mean of 6.2, 15.4, and 26.0 injections, there was a mean change of +4.7, +3.3, and +3.1 letters, respectively. At 1 and 3 years, in 12 451 and 3027 eyes with BRVO-ME, after a mean of 7.1 and 18.2 injections, there was a mean change of +9.5 and +7.7 letters, respectively. At 1 and 3 years, in 9298 and 2264 eyes with CRVO-ME, after a mean of 7.3 and 18.8 injections, there was a mean change of +8.3 and +6.0 letters, respectively (P < 0.01 for all VA changes of > 1 letter). In all 4 conditions, the mean VA increased with the mean number of anti-VEGF injections, eyes with a baseline VA of 20/40 or better tended to lose VA, and eyes with progressively worse baseline VA experienced a progressively greater VA gain at 3 years. Conclusions In practice, patients with nAMD, DME, BRVO-ME, and CRVO-ME showed limited visual outcomes, with patients with nAMD tending to lose VA at 3 and 5 years. Across all 4 disorders, the mean change in VA correlated with treatment intensity at 1, 3, and 5 years. Patients with better baseline VA are more vulnerable to vision loss.
  • Thumbnail Image
    Item
    Multifocal Electroretinography Changes after UBX1325 (Foselutoclax) Treatment in Neovascular Age-Related Macular Degeneration
    (MDPI, 2024-09-19) Macha, Nathan; Yu, Minzhong; Sapieha, Przemyslaw; Klier, Sharon; Ghosh, Anirvan; White, Lorraine; Maturi, Raj K.; Ophthalmology, School of Medicine
    Background/Objectives: The objective of this study was to determine the treatment effect of foselutoclax in neovascular age-related macular degeneration (AMD) by multifocal electroretinography (mfERG) and evaluate mfERG as a potential clinical endpoint in AMD studies. Methods: A total of five subjects were included in the study who had active choroidal neovascularization and a history of at least two anti-vascular endothelial growth factor (VEGF) injections in the last 6 months. Subjects received a 50 µL intravitreal injection of foselutoclax at the baseline visit and Weeks 4, 24, and 28 of the study period. Results: After foselutoclax treatment, the largest improvement in the mfERG N1-P1 response density occurred at Week 8 as three of five subjects achieved a ≥20% gain. In addition, three of five subjects demonstrated a BCVA improvement of ≥5 ETDRS letters over baseline at Weeks 4, 8, and 24. The mean change in BCVA demonstrated statistical significance in Weeks 4 and 8, showing increases of 5 (p = 0.02) and 6.2 (p = 0.02) letters, respectively. Conclusions: Foselutoclax treatment was shown to have the potential to recover outer retinal function as determined by mfERG and BCVA at approximately Week 8 of treatment.
  • Thumbnail Image
    Item
    Prediction of Anti-VEGF Response in Diabetic Macular Edema After 1 Injection
    (2017-05) Shah, Ankoor R.; Yonekawa, Yoshihiro; Todorich, Bozho; Van Laere, Lily; Hussain, Rehan; Woodward, Maria A.; Abbey, Ashkan M.; Wolfe, Jeremy D.; Ophthalmology, School of Medicine
    Purpose With multiple anti-vascular endothelial growth factor and steroid therapies available for diabetic macular edema (DME), there is a need for early determination of the best treatment for a particular patient to prevent irreversible vision loss from chronic DME. In this study, we classify patients as responders or non-responders to anti-vascular endothelial growth factor (VEGF) monotherapy in the treatment of DME after a single anti-VEGF injection. Methods The study was designed as a single center, retrospective, interventional case series. We included patients who received 3 consecutive monthly injections with the same anti-VEGF agent. We excluded patients who were treated for DME in the preceding 3 months with any form of anti-VEGF therapy. Visual acuity and central retinal thickness (CRT) data were followed for one year. Receiver operating characteristic (ROC) curve analysis was performed in order to identify cutoff values for identifying responders. Results 107 eyes were reviewed, with 40 eyes of 34 patients meeting all inclusion criteria. Based on ROC curve analysis, a reduction in CRT by > 15% at 1-month, identified eyes that responded to treatment and had a >25% reduction in CRT at 3-months (sensitivity 0.75, specificity 0.92). Conclusion DME eyes that have early response to anti-VEGF treatment by reduction in CRT will have significant response to treatment by 3 months.
  • Thumbnail Image
    Item
    Two-Year Results of the Phase 3 Randomized Controlled Study of Abicipar in Neovascular Age-Related Macular Degeneration
    (Elsevier, 2021) Khurana, Rahul N.; Kunimoto, Derek; Yoon, Young Hee; Wykoff, Charles C.; Chang, Andrew; Maturi, Raj K.; Agostini, Hansjürgen; Souied, Eric; Chow, David R.; Lotery, Andrew J.; Ohji, Masahito; Bandello, Francesco; Belfort, Rubens, Jr.; Li, Xiao-Yan; Jiao, Jenny; Le, Grace; Kim, Kimmie; Schmidt, Werner; Hashad, Yehia; CEDAR and SEQUOIA Study Groups; Ophthalmology, School of Medicine
    Purpose: To report the 2-year efficacy and safety of abicipar every 8 weeks and quarterly (after initial doses) compared with monthly ranibizumab in patients with treatment-naïve neovascular age-related macular degeneration (nAMD). Design: Two multicenter, randomized, phase 3 clinical trials with identical protocols (CEDAR and SEQUOIA). Analyses used pooled trial data. Participants: The trials enrolled 1888 patients (1 eye/patient) with active choroidal neovascularization secondary to age-related macular degeneration and best-corrected visual acuity (BCVA) of 24 to 73 Early Treatment Diabetic Retinopathy Study letters. Methods: At enrollment, patients were assigned to study eye treatment with abicipar 2 mg every 8 weeks after initial doses at baseline and weeks 4 and 8 (abicipar Q8, n = 630), abicipar 2 mg every 12 weeks after initial doses at baseline and weeks 4 and 12 (abicipar Q12, n = 628), or ranibizumab 0.5 mg every 4 weeks (ranibizumab Q4, n = 630). Main outcome measures: Efficacy measures included stable vision (<15-letter loss in BCVA from baseline) and change from baseline in BCVA and central retinal thickness (CRT). Safety measures included adverse events (AEs). Results: For patients who completed the study, efficacy of abicipar after initial doses was maintained through week 104. At week 104, the proportion of patients with stable vision was 93.0% (396/426), 89.8% (379/422), and 94.4% (470/498); mean change in BCVA from baseline was +7.8 letters, +6.1 letters, and +8.5 letters, and mean change in CRT from baseline was -147 μm, -146 μm, and -142 μm in the abicipar Q8 (14 injections), abicipar Q12 (10 injections), and ranibizumab Q4 (25 injections) groups, respectively. The overall incidence of intraocular inflammation (IOI) AEs was 15.4%, 15.3%, and 0.3% from baseline through week 52 and 16.2%, 17.6%, and 1.3% from baseline through week 104 in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively. Conclusions: Two-year results show efficacy of abicipar Q8 and Q12 in nAMD. First onset of IOI events with abicipar was much reduced in the second year and comparable with ranibizumab (0.8% and 2.3% vs. 1.0%). The extended duration of effect of abicipar allows for quarterly dosing and reduced treatment burden.