BALATON and COMINO: Phase III Randomized Clinical Trials of Faricimab for Retinal Vein Occlusion: Study Design and Rationale

Lars Olof Hattenbach; Francis Abreu; Pablo Arrisi; Karen Basu; Carl J. Danzig; Robyn Guymer; Zdenka Haskova; Jeffrey S. Heier; Aachal Kotecha; Ying Liu; Anat Loewenstein; András Seres; Jeffrey R. Willis; Charles C. Wykoff; Liliana P. Paris

doi:10.1016/j.xops.2023.100302

BALATON and COMINO: Phase III Randomized Clinical Trials of Faricimab for Retinal Vein Occlusion: Study Design and Rationale

Lars Olof Hattenbach, Francis Abreu, Pablo Arrisi, Karen Basu, Carl J. Danzig, Robyn Guymer, Zdenka Haskova, Jeffrey S. Heier, Aachal Kotecha, Ying Liu, Anat Loewenstein, András Seres, Jeffrey R. Willis, Charles C. Wykoff, Liliana P. Paris

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

PURPOSE: Dual inhibition of angiopoietin-2 and VEGF-A with faricimab (Vabysmo) offers excellent visual acuity gains with strong durability in patients with diabetic macular edema (ME) and neovascular age-related macular degeneration. The phase III BALATON/COMINO (NCT04740905/NCT04740931) trials will investigate the efficacy, safety, and durability of faricimab in patients with ME due to retinal vein occlusion (RVO).

DESIGN: Two identically designed global, randomized, double-masked, active comparator-controlled studies.

PARTICIPANTS: Anti-VEGF treatment-naive patients with branch, central, or hemiretinal RVO.

METHODS: Patients were randomized to 6 monthly injections of faricimab 6.0 mg or aflibercept 2.0 mg. From weeks 24 to 72, all patients received faricimab 6.0 mg administered in up to 16-week intervals using an automated treatment algorithm to generate a treat-and-extend-based personalized treatment interval dosing regimen. Personalized treatment interval adjustments were based on changes in central subfield thickness (CST) and best-corrected visual acuity (BCVA).

MAIN OUTCOME MEASURES: Primary end point was noninferiority of faricimab versus aflibercept in mean change from baseline in BCVA (week 24; noninferiority margin: 4 letters). Secondary end points (weeks 0-24) were mean change from baseline in BCVA, CST, and National Eye Institute Visual Function Questionnaire 25 composite score; proportion of patients gaining or avoiding loss of ≥ 15/≥ 10/≥ 5/> 0 letters. Secondary end points (weeks 24-72) were treatment durability (week 68); continuation of weeks 0 to 24 end points. Ocular/nonocular adverse events will be assessed.

RESULTS: In total, 1282 patients across 22 countries were enrolled (BALATON, 553 patients, 149 centers; COMINO, 729 patients, 193 centers).

CONCLUSIONS: Using a novel automated interval algorithm, BALATON/COMINO will evaluate the efficacy and safety of faricimab for ME secondary to RVO and provide key insights into how to personalize treatment.

FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Original language	English (US)
Article number	100302
Pages (from-to)	100302
Journal	Ophthalmology Science
Volume	3
Issue number	3
DOIs	https://doi.org/10.1016/j.xops.2023.100302
State	Published - Sep 2023

Keywords

Angiopoietin-2
Faricimab
Macular edema
Retinal vein occlusion
Vascular endothelial growth factor receptor

ASJC Scopus subject areas

Ophthalmology

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10.1016/j.xops.2023.100302

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Hattenbach, L. O., Abreu, F., Arrisi, P., Basu, K., Danzig, C. J., Guymer, R., Haskova, Z., Heier, J. S., Kotecha, A., Liu, Y., Loewenstein, A., Seres, A., Willis, J. R., Wykoff, C. C., & Paris, L. P. (2023). BALATON and COMINO: Phase III Randomized Clinical Trials of Faricimab for Retinal Vein Occlusion: Study Design and Rationale. Ophthalmology Science, 3(3), 100302. Article 100302. https://doi.org/10.1016/j.xops.2023.100302

Hattenbach, LO, Abreu, F, Arrisi, P, Basu, K, Danzig, CJ, Guymer, R, Haskova, Z, Heier, JS, Kotecha, A, Liu, Y, Loewenstein, A, Seres, A, Willis, JR, Wykoff, CC & Paris, LP 2023, 'BALATON and COMINO: Phase III Randomized Clinical Trials of Faricimab for Retinal Vein Occlusion: Study Design and Rationale', Ophthalmology Science, vol. 3, no. 3, 100302, pp. 100302. https://doi.org/10.1016/j.xops.2023.100302

@article{142458a55d344e41b6006bccc653bcc0,

title = "BALATON and COMINO: Phase III Randomized Clinical Trials of Faricimab for Retinal Vein Occlusion: Study Design and Rationale",

abstract = "PURPOSE: Dual inhibition of angiopoietin-2 and VEGF-A with faricimab (Vabysmo) offers excellent visual acuity gains with strong durability in patients with diabetic macular edema (ME) and neovascular age-related macular degeneration. The phase III BALATON/COMINO (NCT04740905/NCT04740931) trials will investigate the efficacy, safety, and durability of faricimab in patients with ME due to retinal vein occlusion (RVO).DESIGN: Two identically designed global, randomized, double-masked, active comparator-controlled studies.PARTICIPANTS: Anti-VEGF treatment-naive patients with branch, central, or hemiretinal RVO.METHODS: Patients were randomized to 6 monthly injections of faricimab 6.0 mg or aflibercept 2.0 mg. From weeks 24 to 72, all patients received faricimab 6.0 mg administered in up to 16-week intervals using an automated treatment algorithm to generate a treat-and-extend-based personalized treatment interval dosing regimen. Personalized treatment interval adjustments were based on changes in central subfield thickness (CST) and best-corrected visual acuity (BCVA).MAIN OUTCOME MEASURES: Primary end point was noninferiority of faricimab versus aflibercept in mean change from baseline in BCVA (week 24; noninferiority margin: 4 letters). Secondary end points (weeks 0-24) were mean change from baseline in BCVA, CST, and National Eye Institute Visual Function Questionnaire 25 composite score; proportion of patients gaining or avoiding loss of ≥ 15/≥ 10/≥ 5/> 0 letters. Secondary end points (weeks 24-72) were treatment durability (week 68); continuation of weeks 0 to 24 end points. Ocular/nonocular adverse events will be assessed.RESULTS: In total, 1282 patients across 22 countries were enrolled (BALATON, 553 patients, 149 centers; COMINO, 729 patients, 193 centers).CONCLUSIONS: Using a novel automated interval algorithm, BALATON/COMINO will evaluate the efficacy and safety of faricimab for ME secondary to RVO and provide key insights into how to personalize treatment.FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.",

keywords = "Angiopoietin-2, Faricimab, Macular edema, Retinal vein occlusion, Vascular endothelial growth factor receptor",

author = "Hattenbach, {Lars Olof} and Francis Abreu and Pablo Arrisi and Karen Basu and Danzig, {Carl J.} and Robyn Guymer and Zdenka Haskova and Heier, {Jeffrey S.} and Aachal Kotecha and Ying Liu and Anat Loewenstein and Andr{\'a}s Seres and Willis, {Jeffrey R.} and Wykoff, {Charles C.} and Paris, {Liliana P.}",

note = "{\textcopyright} 2023 by the American Academy of Ophthalmology.",

year = "2023",

month = sep,

doi = "10.1016/j.xops.2023.100302",

language = "English (US)",

volume = "3",

pages = "100302",

journal = "Ophthalmology Science",

issn = "2666-9145",

publisher = "Elsevier BV",

number = "3",

}

TY - JOUR

T1 - BALATON and COMINO

T2 - Phase III Randomized Clinical Trials of Faricimab for Retinal Vein Occlusion: Study Design and Rationale

AU - Hattenbach, Lars Olof

AU - Abreu, Francis

AU - Arrisi, Pablo

AU - Basu, Karen

AU - Danzig, Carl J.

AU - Guymer, Robyn

AU - Haskova, Zdenka

AU - Heier, Jeffrey S.

AU - Kotecha, Aachal

AU - Liu, Ying

AU - Loewenstein, Anat

AU - Seres, András

AU - Willis, Jeffrey R.

AU - Wykoff, Charles C.

AU - Paris, Liliana P.

PY - 2023/9

Y1 - 2023/9

N2 - PURPOSE: Dual inhibition of angiopoietin-2 and VEGF-A with faricimab (Vabysmo) offers excellent visual acuity gains with strong durability in patients with diabetic macular edema (ME) and neovascular age-related macular degeneration. The phase III BALATON/COMINO (NCT04740905/NCT04740931) trials will investigate the efficacy, safety, and durability of faricimab in patients with ME due to retinal vein occlusion (RVO).DESIGN: Two identically designed global, randomized, double-masked, active comparator-controlled studies.PARTICIPANTS: Anti-VEGF treatment-naive patients with branch, central, or hemiretinal RVO.METHODS: Patients were randomized to 6 monthly injections of faricimab 6.0 mg or aflibercept 2.0 mg. From weeks 24 to 72, all patients received faricimab 6.0 mg administered in up to 16-week intervals using an automated treatment algorithm to generate a treat-and-extend-based personalized treatment interval dosing regimen. Personalized treatment interval adjustments were based on changes in central subfield thickness (CST) and best-corrected visual acuity (BCVA).MAIN OUTCOME MEASURES: Primary end point was noninferiority of faricimab versus aflibercept in mean change from baseline in BCVA (week 24; noninferiority margin: 4 letters). Secondary end points (weeks 0-24) were mean change from baseline in BCVA, CST, and National Eye Institute Visual Function Questionnaire 25 composite score; proportion of patients gaining or avoiding loss of ≥ 15/≥ 10/≥ 5/> 0 letters. Secondary end points (weeks 24-72) were treatment durability (week 68); continuation of weeks 0 to 24 end points. Ocular/nonocular adverse events will be assessed.RESULTS: In total, 1282 patients across 22 countries were enrolled (BALATON, 553 patients, 149 centers; COMINO, 729 patients, 193 centers).CONCLUSIONS: Using a novel automated interval algorithm, BALATON/COMINO will evaluate the efficacy and safety of faricimab for ME secondary to RVO and provide key insights into how to personalize treatment.FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

AB - PURPOSE: Dual inhibition of angiopoietin-2 and VEGF-A with faricimab (Vabysmo) offers excellent visual acuity gains with strong durability in patients with diabetic macular edema (ME) and neovascular age-related macular degeneration. The phase III BALATON/COMINO (NCT04740905/NCT04740931) trials will investigate the efficacy, safety, and durability of faricimab in patients with ME due to retinal vein occlusion (RVO).DESIGN: Two identically designed global, randomized, double-masked, active comparator-controlled studies.PARTICIPANTS: Anti-VEGF treatment-naive patients with branch, central, or hemiretinal RVO.METHODS: Patients were randomized to 6 monthly injections of faricimab 6.0 mg or aflibercept 2.0 mg. From weeks 24 to 72, all patients received faricimab 6.0 mg administered in up to 16-week intervals using an automated treatment algorithm to generate a treat-and-extend-based personalized treatment interval dosing regimen. Personalized treatment interval adjustments were based on changes in central subfield thickness (CST) and best-corrected visual acuity (BCVA).MAIN OUTCOME MEASURES: Primary end point was noninferiority of faricimab versus aflibercept in mean change from baseline in BCVA (week 24; noninferiority margin: 4 letters). Secondary end points (weeks 0-24) were mean change from baseline in BCVA, CST, and National Eye Institute Visual Function Questionnaire 25 composite score; proportion of patients gaining or avoiding loss of ≥ 15/≥ 10/≥ 5/> 0 letters. Secondary end points (weeks 24-72) were treatment durability (week 68); continuation of weeks 0 to 24 end points. Ocular/nonocular adverse events will be assessed.RESULTS: In total, 1282 patients across 22 countries were enrolled (BALATON, 553 patients, 149 centers; COMINO, 729 patients, 193 centers).CONCLUSIONS: Using a novel automated interval algorithm, BALATON/COMINO will evaluate the efficacy and safety of faricimab for ME secondary to RVO and provide key insights into how to personalize treatment.FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

KW - Angiopoietin-2

KW - Faricimab

KW - Macular edema

KW - Retinal vein occlusion

KW - Vascular endothelial growth factor receptor

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DO - 10.1016/j.xops.2023.100302

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AN - SCOPUS:85154570370

SN - 2666-9145

VL - 3

SP - 100302

JO - Ophthalmology Science

JF - Ophthalmology Science

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M1 - 100302

ER -

BALATON and COMINO: Phase III Randomized Clinical Trials of Faricimab for Retinal Vein Occlusion: Study Design and Rationale

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