Faricimab

Faricimab
Monoclonal antibody
TypeWhole antibody
SourceHumanized
TargetVEGF-A, angiopoietin 2[1]
Clinical data
Trade namesVabysmo
Other namesRO6867461; RG7716; faricimab-svoa
License data
Pregnancy
category
Routes of
administration		Intravitreal
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
UNII
KEGG
Chemical and physical data
FormulaC6506H9968N1724O1026S45
Molar mass130197.05 g·mol−1

Faricimab, sold under the brand name Vabysmo (/vəˈbaɪzmoʊ/ və-BYEZ-mow), is a monoclonal antibody used for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).[1][8] Faricimab is the first bispecific monoclonal antibody[9] to target both vascular endothelial growth factor (VEGF)[1] and angiopoietin 2 (Ang-2).[1] By targeting these pathways, faricimab stabilizes blood vessels in the retina.[9] It is given by intravitreal injection (injection into the eye) by an ophthalmologist.[1]

Faricimab was developed by Roche in Penzberg (Roche Innovation Center Munich).[10] Faricimab was approved for medical use in the United States in January 2022,[8][11] and in the European Union in September 2022.[7]

Medical uses

Faricimab is indicated for treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).[1]

Adverse effects

The most common adverse reaction reported in people receiving faricimab include conjunctival bleeding.[1]

Contraindications

Contraindications to injection of faricimab include active infection in or around the eye, active inflammation in the eye (uveitis), and prior allergic reactions to receiving the drug (hypersensitivity).[1]

Special populations

Pregnancy

There are no adequate and well-controlled studies of faricimab administration in pregnant women.[1]

Breast feeding

There is no information regarding faricimab accumulation in breast milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. However, the drug company states that many drugs are transferred in human milk with the potential for absorption and adverse reactions in the breastfed child.[1]

Fertility

No studies on the effects of faricimab on human fertility have been conducted and it is not known whether faricimab can affect reproduction. Based on its mechanism of action, treatment with may pose a risk to reproductive capacity.[1]

Pharmacology

Faricimab is a 150kDa-sized bispecific antibody whose molecular structure allows a high affinity bond to both vascular endothelial growth factor A (VEGF-A) and Angiopoietin (Ang-2).[9] By blocking the action of these two growth factors, faricimab decreases migration and replication of endothelial cells allowing for stabilization of vascular structures, thereby decreasing vascular leakage.[12][13][14] Faricimab has shown improved and sustained efficacy in comparison to agents that only target the VEGF pathway.[12]

History

In 2016, pre-clinical studies looking at the mechanism of action behind faricimab showed that by blocking Ang-2, one of the drug's targets, there was decreased endothelial barrier breakdown in blood vessels.[12] In 2017, phase I studies in neovascular age related macular degeneration (nAMD) showed that the drug was safe to use in people and well tolerated.[12]

Society and culture

On 21 July 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Vabysmo, intended for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DME).[15] The applicant for this medicinal product is Roche Registration GmbH.[15] Faricimab was approved for medical use in the European Union in September 2022.[7][16]

Names

Faricimab is the International Nonproprietary Name (INN).[17] Faricimab was formerly named RG7716.[18]

Research

Two phase II trials evaluated faricimab's efficacy and safety in comparison to ranibizumab and showed that faricimab received every 16 weeks and every twelve weeks was comparable to ranibizumab received every four weeks in visual acuity and imaging outcomes.[12] In 2019, two phase III multi-center randomized studies TENAYA and LUCERNE were initiated on 1,200 participants with neovascular age related macular degeneration (nAMD) to evaluate faricimab's safety, efficacy, and durability against aflibercept.[12] Both studies reached its primary endpoints and showed that faricimab given at up to every 16 weeks was non-inferior to aflibercept administered every 8 weeks. Faricimab demonstrated its potential to extend the time between intravitreal injections in nAMD patients.[19]

Diabetic macular edema

One phase II trial evaluated faricimab's efficacy and safety in comparison to ranibizumab and showed clinically meaningful and statistically significant improvements in visual acuity.[12][20] Two phase III multi-center randomized studies were completed on 1,891 diabetic participants with diabetic macular edema (DME).[12][21]

Branch and central retinal vein occlusion macular edema

In two phase III trials, faricimab met the primary endpoint of non-inferior visual acuity gains when compared with aflibercept in 553 participants with macular edema due to branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) in the BALATON and COMINO studies.[22][23][24]

References

  1. ^ a b c d e f g h i j k l "Vabysmo- faricimab injection, solution". DailyMed. 7 February 2022. Archived from the original on 21 February 2022. Retrieved 20 February 2022.
  2. ^ a b "Vabysmo". Therapeutic Goods Administration (TGA). 9 November 2022. Retrieved 29 April 2023.
  3. ^ "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 21 December 2022. Archived from the original on 3 April 2022. Retrieved 2 January 2023.
  4. ^ "Vabysmo (Roche Products Pty Ltd)". Therapeutic Goods Administration (TGA). 28 September 2022. Archived from the original on 13 October 2022. Retrieved 29 April 2023.
  5. ^ "Summary Basis of Decision - Vabysmo". Health Canada. 31 August 2022. Archived from the original on 29 September 2022. Retrieved 29 September 2022.
  6. ^ "Vabysmo Product information". Health Canada. 25 April 2012. Archived from the original on 1 October 2022. Retrieved 30 September 2022.
  7. ^ a b c "Vabysmo EPAR". European Medicines Agency (EMA). 19 July 2022. Archived from the original on 14 October 2022. Retrieved 14 October 2022.
  8. ^ a b "FDA approves Roche's Vabysmo, the first bispecific antibody for the eye, to treat two leading causes of vision loss" (Press release). Roche. 31 January 2022. Archived from the original on 31 January 2022. Retrieved 31 January 2022.
  9. ^ a b c Nicolò M, Ferro Desideri L, Vagge A, Traverso CE (March 2021). "Faricimab: an investigational agent targeting the Tie-2/angiopoietin pathway and VEGF-A for the treatment of retinal diseases". Expert Opinion on Investigational Drugs. 30 (3): 193–200. doi:10.1080/13543784.2021.1879791. PMID 33471572. S2CID 231665201.
  10. ^ "Neue Netzhaut-Therapie aus Penzberg". www.merkur.de (in German). 2 September 2023. Retrieved 12 August 2024.
  11. ^ "FDA approves faricimab for treatment of wet AMD, DME". Ophthalmology Times. 28 January 2022. Archived from the original on 29 January 2022. Retrieved 29 January 2022.
  12. ^ a b c d e f g h Khan M, Aziz AA, Shafi NA, Abbas T, Khanani AM (August 2020). "Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab". Cells. 9 (8): 1869. doi:10.3390/cells9081869. PMC 7464130. PMID 32785136.
  13. ^ Iglicki M, González DP, Loewenstein A, Zur D (February 2022). "Next-generation anti-VEGF agents for diabetic macular oedema". Eye. 36 (2): 273–277. doi:10.1038/s41433-021-01722-8. PMC 8807622. PMID 34373607. Archived from the original on 30 July 2022. Retrieved 30 July 2022.
  14. ^ Fenner BJ, Cheung CM, Sim SS, Lee WK, Staurenghi G, Lai TY, et al. (February 2022). "Evolving treatment paradigms for PCV". Eye. 36 (2): 257–265. doi:10.1038/s41433-021-01688-7. PMC 8807588. PMID 34262165. Archived from the original on 30 July 2022. Retrieved 30 July 2022.
  15. ^ a b "Vabysmo: Pending EC decision". European Medicines Agency. 22 July 2022. Archived from the original on 28 July 2022. Retrieved 29 July 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  16. ^ "Vabysmo Product information". Union Register of medicinal products. Archived from the original on 27 October 2022. Retrieved 3 March 2023.
  17. ^ World Health Organization (2018). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 80". WHO Drug Information. 32 (3). hdl:10665/330907.
  18. ^ Kaplon H, Chenoweth A, Crescioli S, Reichert JM (January 2022). "Antibodies to watch in 2022". mAbs. 14 (1): 2014296. doi:10.1080/19420862.2021.2014296. PMC 8765076. PMID 35030985.
  19. ^ Heier JS, Khanani AM, Quezada Ruiz C, Basu K, Ferrone PJ, Brittain C, et al. (February 2022). "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" (PDF). Lancet. 399 (10326): 729–740. doi:10.1016/s0140-6736(22)00010-1. PMID 35085502. S2CID 246242760. Archived (PDF) from the original on 31 May 2023. Retrieved 10 March 2024.
  20. ^ "Phase II data support potential for Roche's novel anti-VEGF/anti-angiopoietin-2 bispecific antibody, RG7716, for people with diabetic macular edema". Roche (Press release). Archived from the original on 17 February 2022. Retrieved 17 February 2022.
  21. ^ Sharma A, Kumar N, Parachuri N, Karanam D, Kuppermann BD, Bandello F, Regillo CD (April 2022). "Faricimab phase 3 DME trial significance of personalized treatment intervals (PTI) regime for future DME trials". Eye. 36 (4): 679–680. doi:10.1038/s41433-021-01831-4. PMC 8956679. PMID 34718339. S2CID 240157515.
  22. ^ Clinical trial number NCT04740905 for "A Study to Evaluate the Efficacy and Safety of Faricimab in Participants With Macular Edema Secondary to Branch Retinal Vein Occlusion (BALATON)" at ClinicalTrials.gov
  23. ^ Clinical trial number NCT04740931 for "A Study to Evaluate the Efficacy and Safety of Faricimab in Participants With Macular Edema Secondary to Central Retinal or Hemiretinal Vein Occlusion (COMINO)" at ClinicalTrials.gov
  24. ^ "Roche touts positive top-line Phase III results for Vabysmo". The Pharma Letter. Archived from the original on 28 October 2022. Retrieved 28 October 2022.
  • Clinical trial number NCT03622580 for "A Study to Evaluate the Efficacy and Safety of Faricimab (RO6867461) in Participants With Diabetic Macular Edema (YOSEMITE)" at ClinicalTrials.gov
  • Clinical trial number NCT03622593 for "A Study to Evaluate the Efficacy and Safety of Faricimab (RO6867461) in Participants With Diabetic Macular Edema (RHINE)" at ClinicalTrials.gov
  • Clinical trial number NCT03823287 for "A Study to Evaluate the Efficacy and Safety of Faricimab in Participants With Neovascular Age-Related Macular Degeneration (TENAYA)" at ClinicalTrials.gov
  • Clinical trial number NCT03823300 for "A Study to Evaluate the Efficacy and Safety of Faricimab in Participants With Neovascular Age-Related Macular Degeneration (LUCERNE)" at ClinicalTrials.gov