• Roche/Genentech does not provide any specific recommendations for dosing when switching from previous anti-VEGF therapies to Vabysmo, beyond the dosing recommendations in the local prescribing information.
• The recommended dosing of Vabysmo for both DME and nAMD is 6 mg via IVT injection every 4 weeks for the first 4 doses, followed by 6 mg via IVT injection at intervals of up to every 16 weeks.
• Roche/Genentech does not provide any recommendations for when to switch from previous anti-VEGF therapies to Vabysmo. However, the treatment with previous therapy was accounted for during enrolment of the Phase 3 clinical studies.
• Patients with DME who previously received IVT anti-VEGF agents were eligible for study entry only if the treatment was not administered in the prior 3 months.
• Only treatment-naive patients with nAMD were enrolled in the studies. Patients who previously received anti-VEGF treatment were not eligible for study entry.
• A period of approximately 5 times the elimination half-life is generally considered sufficient for washout.

DME=diabetic macular edema

IVT=intravitreal

nAMD=neovascular age-related macular degeneration

Q4W=every 4 weeks

Q8W=every 8 weeks

Q12W=every 12 weeks

Q16W=every 16 weeks

VEGF=vascular endothelial growth factor

Roche/Genentech does not provide any specific recommendations for dosing when switching from previous anti-VEGF therapies to Vabysmo, beyond the dosing recommendations in the local prescribing information.

The recommended dosing of Vabysmo for both DME and nAMD is 6 mg via IVT injection every 4 weeks for the first 4 doses, followed by 6 mg via IVT injection at intervals of up to every 16 weeks.[1]

Monitoring between the dosing visits should be scheduled based on the patient's status and at the physician's discretion.[1]

The 6 mg dose was based on data from preclinical models, clinical outcomes from Phase 1 [2] and 2 [3-5] studies and clinical pharmacokinetic and pharmacodynamic assessments.

For Phase 3 studies, the 6 mg dose was selected to maximize the potential for a durable treatment effect on the basis of a pharmacokinetic and pharmacodynamic model.[6]

Phase 3 YOSEMITE and RHINE studies in DME patients

YOSEMITE (NCT03622580) and RHINE (NCT03622593) were two identical, randomized, multicenter, double-masked, global Phase 3 trials designed to evaluate the efficacy and safety of Vabysmo compared with aflibercept in patients with DME.[7]

The two Vabysmo treatment groups received either four initial 6 mg doses Q4W up to Week 12, followed by dosing interval adjustments according to a personalized treatment interval or six initial 6 mg doses Q4W up to Week 20, followed by a dosing interval increase to Q8W.[7]

Phase 3 LUCERNE and TENAYA studies in nAMD patients

TENAYA (NCT03823287) and LUCERNE (NCT03283300) were two identical, randomized, multicenter, double-masked, global Phase 3 trials to evaluate the efficacy, safety, and durability of Vabysmo compared with aflibercept in patients with nAMD.[8]

The Vabysmo treatment group received four initial 6 mg doses Q4W, up to Week 12, then dosing intervals were increased to either Q8W, Q12W or Q16W through Week 60 based on protocol-defined disease activity criteria.[8]

Roche/Genentech does not provide any recommendations for when to switch from previous anti-VEGF therapies to Vabysmo.

However, the treatment with previous therapy was accounted for during enrolment of the Phase 3 clinical studies.

Eligibility criteria in the YOSEMITE and RHINE studies in DME patients

Patients who previously received IVT anti-VEGF agents were eligible for study entry only if the treatment was not administered in the prior 3 months.[9,10]

Eligibility criteria in the TENAYA and LUCERNE studies in nAMD patients

Only treatment-naive patients were enrolled in the studies. Patients who previously received anti-VEGF treatment were not eligible for study entry.[11,12]

Washout period of IVT anti-VEGF therapy

A period of approximately 5 times the elimination half-life is generally considered sufficient for washout.[13,14] The appropriate washout period will depend on the vitreous elimination half-life of the previous IVT anti-VEGF drug. We refer the interested reader to the prescribing information of the respective drugs for more information.

1. Roche Internal Regulatory Document (Vabysmo Core Data Sheet 4.0)(Accessed on 7 August 2023).
2. European Medicines Agency (EMA). Vabysmo: EPAR - Public Assessment Report. Available at https://www.ema.europa.eu/documents/assessment-report/vabysmo-epar-public-assessment-report_en.pdf. Accessed on August 7, 2023.
3. Sahni J, Patel S, Dugel P, et al. Simultaneous Inhibition of Angiopoietin-2 and Vascular Endothelial Growth Factor-A with Faricimab in Diabetic Macular Edema: BOULEVARD Phase 2 Randomized Trial. Ophthalmology 2019;126:1155-1170. https://www.ncbi.nlm.nih.gov/pubmed/30905643
4. Khanani A, Patel S, Ferrone P, et al. Efficacy of Every Four Monthly and Quarterly Dosing of Faricimab vs Ranibizumab in Neovascular Age-Related Macular Degeneration: The STAIRWAY Phase 2 Randomized Clinical Trial. JAMA Ophthalmol 2020;138:964-972. https://www.ncbi.nlm.nih.gov/pubmed/32729897
5. Sahni J, Dugel P, Patel S, et al. Safety and Efficacy of Different Doses and Regimens of Faricimab vs Ranibizumab in Neovascular Age-Related Macular Degeneration: The AVENUE Phase 2 Randomized Clinical Trial. JAMA Ophthalmol 2020;138:955-963. https://www.ncbi.nlm.nih.gov/pubmed/32729888
6. Hutton-Smith L, Gaffney E, Byrne H, et al. A Mechanistic Model of the Intravitreal Pharmacokinetics of Large Molecules and the Pharmacodynamic Suppression of Ocular Vascular Endothelial Growth Factor Levels by Ranibizumab in Patients with Neovascular Age-Related Macular Degeneration. Mol Pharm 2016;13:2941-50. https://www.ncbi.nlm.nih.gov/pubmed/26726925
7. Wykoff C, Abreu F, Adamis A, et al. Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials. Lancet 2022;399:741-755. https://www.ncbi.nlm.nih.gov/pubmed/35085503
8. Heier J, Khanani A, Quezada RC, et al. Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials. Lancet 2022;399:729-740. https://www.ncbi.nlm.nih.gov/pubmed/35085502
9. Roche Internal Clinical Study Report (YOSEMITE)(Accessed on 1 August 2023).
10. Roche Internal Clinical Study Report (RHINE)(Accessed on 1 August 2023).
11. Roche Internal Clinical Study Report (TENAYA)(Accessed on 1 August 2023).
12. Roche Internal Clinical Study Report (LUCERNE)(Accessed on 1 August 2023).
13. European Medicines Agency. Guideline on the investigation of bioequivalence. Available at https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-investigation-bioequivalence-rev1_en.pdf. Accessed on August 4, 2023.
14. US Food and Drug Administration. Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application. Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bioequivalence-studies-pharmacokinetic-endpoints-drugs-submitted-under-abbreviated-new-drug. Accessed on August 4, 2023.