scholarly journals Biosimilar SB11 versus reference ranibizumab in neovascular age-related macular degeneration: 1-year phase III randomised clinical trial outcomes

2021 ◽  
pp. bjophthalmol-2021-319637
Author(s):  
Neil M Bressler ◽  
Miroslav Veith ◽  
Jan Hamouz ◽  
Jan Ernest ◽  
Dominik Zalewski ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Randomised Clinical Trial ◽  
Age Related Macular Degeneration ◽  
Phase Iii ◽  
Treatment Groups ◽  
Age Related ◽  
Parallel Group ◽  
Central Subfield Thickness ◽  
Trial Outcomes ◽  
Full Analysis

Background/AimsTo provide longer-term data on efficacy, safety, immunogenicity and pharmacokinetics (PK) of ranibizumab biosimilar SB11 compared with the reference ranibizumab (RBZ) in patients with neovascular age-related macular degeneration (nAMD).MethodsSetting: Multicentre. Design: Randomised, double-masked, parallel-group, phase III equivalence study. Patient population: ≥50 years old participants with nAMD (n=705), one ‘study eye’. Intervention: 1:1 randomisation to monthly intravitreal injection of 0.5 mg SB11 or RBZ. Main outcome measures: Visual efficacy endpoints, safety, immunogenicity and PK up to 52 weeks.ResultsBaseline and disease characteristics were comparable between treatment groups. Of 705 randomised participants (SB11: n=351; RBZ: n=354), 634 participants (89.9%; SB11: n=307; RBZ: n=327) completed the study until week 52. Previously reported equivalence in primary efficacy remained stable up to week 52 and were comparable between SB11 and RBZ. The adjusted treatment difference between SB11 and RBZ in full analysis set at week 52 of change from baseline in best-corrected visual acuity was −0.6 letters (90% CI −2.1 to 0.9) and of change from baseline in central subfield thickness was −14.9 µm (95% CI –25.3 to –4.5). The incidence of ocular treatment-emergent adverse events (TEAEs) (SB11: 32.0% vs RBZ: 29.7%) and serious ocular TEAE (SB11: 2.9% vs RBZ: 2.3%) appeared comparable between treatment groups, and no new safety concerns were observed. The PK and immunogenicity profiles were comparable, with a 4.2% and 5.5% cumulative incidence of antidrug antibodies up to week 52 for SB11 and RBZ, respectively.ConclusionsLonger-term results of this study further support the biosimilarity established between SB11 and RBZ.

scholarly journals The role of future treatments in the management of neovascular age-related macular degeneration in Europe

2021 ◽  
pp. 112067212110183
Author(s):  
Laurent Kodjikian ◽  
Carl Joe Mehanna ◽  
Salomon-Yves Cohen ◽  
François Devin ◽  
Sam Razavi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Phase Iii ◽  
Vascular Endothelial ◽  
Real World Data ◽  
Phase Iii Clinical Trials ◽  
Age Related ◽  
Injection Frequency ◽  
Endothelial Growth Factor

Anti-vascular endothelial growth factor (VEGF) agents have transformed the management of patients with neovascular age-related macular degeneration (nAMD) over the past two decades. However, as more long-term real-world data become available, it is clear that treatment outcomes are inferior to those reported in large, controlled clinical trials. This is largely driven by undertreatment, that is, not maintaining a consistent injection frequency to achieve sustained VEGF suppression, whether due to patient non-compliance, an important injection burden, or non/incomplete anatomical response. Newer therapeutic advances under evaluation hold promise in achieving more, for less. We review the latest drugs currently in or having successfully finished phase III clinical trials, and determine their potential place in the management of patients with nAMD in Europe.

Relationship between Aflibercept Efficacy and Genetic Variants of Genes Associated with Neovascular Age-Related Macular Degeneration: The BIOIMAGE Trial

2020 ◽  
Vol 243 (6) ◽  
pp. 461-470
Author(s):  
Anniken Burés Jelstrup ◽  
Esther Pomares ◽  
Rafael Navarro ◽  
Keyword(s):  
Macular Degeneration ◽  
Genetic Variants ◽  
Treatment Efficacy ◽  
Retinal Pigment ◽  
Predictive Biomarkers ◽  
Age Related Macular Degeneration ◽  
Phase Iii ◽  
Extension Phase ◽  
Open Label ◽  
Age Related

<b><i>Purpose:</i></b> To identify the genetic variants of the vascular endothelial growth factor (VEGF) pathway genes and other genes associated with neovascular age-related macular degeneration (nAMD) as possible predictive biomarkers of a favorable treatment response to aflibercept. <b><i>Design:</i></b> A 52-week (with extension phase: 104-week), prospective, open-label, single-arm, multicenter, phase IV trial was conducted in Spain. <b><i>Participants:</i></b> Patients with nAMD were enrolled. <b><i>Methods:</i></b> Aflibercept was administered every 8 weeks until week 48 (after 1-monthly loading doses over 3 months). After week 48, the interval between visits for aflibercept administration was extended by 2 weeks per visit to a maximum of 12 weeks if no evidence of disease activity was observed. A total of 338 SNPs in 90 genes associated with nAMD were analyzed. <b><i>Main Outcome Measures:</i></b> Efficacy was evaluated mainly with best-corrected visual acuity (BCVA), and adverse events (AEs) were reported. Treatment efficacy was defined as an increase in BCVA ≥15 letters versus the baseline visit. Univariate and multivariate logistic regressions were used to associate single-nucleotide polymorphisms (SNPs) and treatment efficacy. <b><i>Results:</i></b> 194 nonconsecutive patients were enrolled, 170 completed the 52-week follow-up, and of the 85 patients who started the extension phase, 77 completed this phase. Mean BCVA increased from baseline to weeks 52 and 104 by 9 and 10 letters (<i>p</i> = 0.0001 for both), respectively. The percentages of patients gaining ≥15 letters in weeks 52 and 104 were 33 and 31%, respectively. Multivariate logistic regression showed significant associations of 6 SNPs (in 6 genes) with treatment efficacy: rs12366035 (<i>VEGFB</i>; TT; odds ratio [OR] 217), rs25681 (<i>C5</i>; AA/AG; OR 19.7/8.3), rs17793056 (<i>CX3CR1</i>; CT/CC; OR 8.1/6.2), rs1800775 (<i>CETP</i>; CC; OR 6.6), rs2069845 (<i>IL6</i>; GG/AA; OR 5.6/3.3), and rs13900 (<i>CCL2</i>; CT; OR 4.0). One percent of the patients reported arteriothrombolic events related to aflibercept (cerebrovascular accident) according to the Antiplatelet Trialist Collaboration, and 2% reported serious ocular (retinal pigment epithelial tear, retinal tear, and endophthalmitis) and systemic (cardiac failure, hypersensitivity, and transient ischemic attack) AEs related to aflibercept. <b><i>Conclusions:</i></b> Results suggest strong pharmacogenetic associations between one genetic variant of <i>VEGFB</i> (TT, rs12366035) and<i> C5</i> (AA, rs12366035) genes and the BCVA response after 52-week aflibercept treatment in patients with nAMD. Likewise, the results support the efficacy of aflibercept observed in phase III studies and a good safety profile.

scholarly journals Aflibercept for age-related macular degeneration: 4-year outcomes of a ‘treat-and-extend’ regimen with exit-strategy

2020 ◽  
pp. bjophthalmol-2020-316514
Author(s):  
Damian Jaggi ◽  
Thanoosha Nagamany ◽  
Andreas Ebneter ◽  
Marion Munk ◽  
Sebastian Wolf ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Long Term Outcomes ◽  
Treat And Extend ◽  
Age Related ◽  
Central Subfield Thickness ◽  
Treatment Naïve ◽  
Treat And Extend Regimen

AimTo report long-term outcomes on best-corrected visual acuity (BCVA) and treatment intervals with a treat-and-extend (T&E) regimen in patients with neovascular age-related macular degeneration (nAMD).MethodsThis observational study included treatment-naïve patients with nAMD, treated with aflibercept. A specific T&E protocol without a loading phase and predefined exit criteria was administered. After reaching predefined ‘exit-criteria’, the treatment period was complete, and patients were observed three monthly.ResultsEighty-two patients with a follow-up period of ≥2 years were included. BCVA (mean±SD, ETDRS letters) increased from 51.9±25.2 at baseline to 63.7±17.7 (p<0.0001) at 1 year, 61.7±18.5 (p<0.0001) at 2 years, 62.4±19.5 (p<0.0001, n=61) at 3 years and remained insignificantly higher than baseline at 4 years at 58.5±24.3 (p=0.22). Central subfield thickness (mean±SD, μm) decreased significantly from 387.5±107.6 (p<0.0001) at baseline to 291.9±65.5 (p<0.0001) at 1 year, and remained significantly lower until 4 years at 289.0±59.4 (p<0.0001). Treatment intervals (mean±SD, weeks) could be extended up to 9.3±3.1 weeks at 1 year and remained at 11.2±3.5 weeks at 4 years. Twenty-nine (35%) patients reached exit criteria and continued with three monthly observation only.ConclusionsAfter 4 years of treatment, initial vision gains were maintained with a reasonable treatment burden, even without an initial loading phase. Our results on functional outcomes are comparable with large controlled studies.

scholarly journals Functional versus functional and anatomical criteria-guided ranibizumab treatment in patients with neovascular age-related macular degeneration – results from the randomized, phase IIIb OCTAVE study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Giovanni Staurenghi ◽  
Justus G. Garweg ◽  
Bianca S. Gerendas ◽  
Wayne Macfadden ◽  
Boris Gekkiev ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Comparable Group ◽  
Link Type ◽  
Age Related ◽  
Group I ◽  
Central Subfield Thickness ◽  
Phase Iiib ◽  
Group Ii ◽  
Ranibizumab Treatment

Abstract Background To evaluate the efficacy and safety of two individualized ranibizumab retreatment schemes in neovascular age-related macular degeneration. Methods Patients (N = 671) were randomized (1:1) to receive three initial monthly ranibizumab 0.5 mg injections, then retreatment guided by either best-corrected visual acuity (BCVA) loss (Group I) or BCVA loss and/or signs of disease activity on optical coherence tomography (OCT; Group II). The study was terminated prematurely and the decision to discontinue the study was made by the sponsor. Efficacy analyses were performed on patients who completed 12 months of the originally planned 24-month study. Safety analyses are presented for all safety analyzable patients. Results Of 671 randomized patients, 305 completed 12 months of the study. For the 12-month completers, baseline mean (standard deviation) BCVA and reading-center evaluated central subfield thickness (CSFT) were comparable [Group I: 60.9 (13.10) letters and 517.7(201.79) μm; Group II: 60.2 (12.21) letters and 515.3 (198.37) μm]. The change from baseline at Month 12 in BCVA was 6.7 (13.48) letters in Group I and 8.3 (13.53) letters in Group II and the change in CSFT was − 161.3 (163.48) μm and − 175.3 (170.45) μm, respectively. The mean number of ranibizumab injections was 8.2 in Group I and 8.4 in Group II. Conclusion Ranibizumab treatment resulted in visual and anatomic gains at 12 months for both retreatment strategies, with a trend in favor of OCT-guided vs BCVA loss guided retreatment. No new safety signals were seen. Trial registration www.ClinicalTrials.gov (NCT01780935). Registered 31 January 2013.

The Evidence Supporting Ranibizumab in the Treatment of Neovascular Age-related Macular Degeneration

2013 ◽  
Vol 07 (02) ◽  
pp. 102
Author(s):  
Simon P Kelly ◽  
Winfried Amoaku ◽  
◽  
Keyword(s):  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Phase Iii ◽  
Dosing Regimen ◽  
Good Safety Profile ◽  
Age Related ◽  
Optimal Dosing ◽  
Increased Risk ◽  
Large Phase ◽  
Wet Amd

The efficacy and safety of ranibizumab in neovascular age-related macular degeneration (AMD) or ‘wet AMD’ has been demonstrated in the large phase III ANCHOR and MARINA trials. Further studies including the PIER, PrONTO, EXCITE and SUSTAIN trials have also evaluated the optimal dosing regimen of ranibizumab. Various head-to-head studies have compared the anti-angiogenic treatments for wet AMD. The CATT and IVAN trials compared the safety and efficacy of ranibizumab with off-label use of bevacizumab and raised concern about an increased risk of ocular and systemic adverse events (AEs) in patients receiving bevacizumab compared with those receiving ranibizumab. Studies such as SAILOR and HORIZON have shown that ranibizumab has a good safety profile and is well tolerated for over 4 years with few serious ocular and systemic AEs.

scholarly journals Gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration: 1 year follow-up of a phase 1 randomised clinical trial

The Lancet ◽  
2015 ◽  
Vol 386 (10011) ◽  
pp. 2395-2403 ◽  
Author(s):  
Elizabeth P Rakoczy ◽  
Chooi-May Lai ◽  
Aaron L Magno ◽  
Matthew E Wikstrom ◽  
Martyn A French ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Gene Therapy ◽  
Macular Degeneration ◽  
Phase 1 ◽  
Randomised Clinical Trial ◽  
Age Related Macular Degeneration ◽  
Age Related
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