Chemistry:Ranibizumab

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Short description: Pharmaceutical drug
Ranibizumab
Monoclonal antibody
TypeFab fragment
SourceHumanized (from mouse)
TargetVascular endothelial growth factor A (VEGF-A)
Clinical data
Trade namesLucentis, others
AHFS/Drugs.comMonograph
MedlinePlusa607044
License data
Pregnancy
category
Routes of
administration		Intravitreal injection
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-lifeApprox. 9 days[4]
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC2158H3282N562O681S12
Molar mass48379.97 g·mol−1
 ☒N☑Y (what is this?)  (verify)

Ranibizumab, sold under the brand name Lucentis among others, is a monoclonal antibody fragment (Fab) created from the same parent mouse antibody as bevacizumab. It is an anti-angiogenic[12] that is approved to treat the "wet" type of age-related macular degeneration (AMD, also ARMD), diabetic retinopathy, and macular edema due to branch retinal vein occlusion or central retinal vein occlusion.

Ranibizumab was developed by Genentech and marketed by them in the United States, and elsewhere by Novartis,[13] under the brand name Lucentis.[4][13][14] Ranibizumab (Lucentis) was approved for medical use in the United States in June 2006,[14][4] and in the European Union in January 2007.

Medical uses

In the United States, ranibizumab is indicated for the treatment of neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema, diabetic retinopathy, and myopic choroidal neovascularization.[4][15]

In the European Union, ranibizumab is indicated for the treatment of neovascular (wet) age-related macular degeneration, visual impairment due to diabetic macular edema, proliferative diabetic retinopathy, visual impairment due to macular edema secondary to retinal vein occlusion, and visual impairment due to choroidal neovascularisation.[8][9][10]

It is often used for age-related wet macular degeneration.[16] Its effectiveness is similar to that of bevacizumab[17][18] and aflibercept.[19] A 2017 systematic review update found that while ranibizumab and bevacizumab provide similar functional outcomes in diabetic macular edema, there is low-certainty evidence suggesting that ranibizumab is more effective in reducing central retinal thickness than bevacizumab.[20]

Side effects

A 2014 Cochrane review did not find a difference between bevacizumab and ranibizumab in deaths or total severe side effects when used for macular degeneration.[21] There, however, was not a lot of evidence, and thus this conclusion is not that certain.[21]

Ranibizumab does appear to result in a lower risk of stomach and intestinal problems.[21] It is also associated with a low rate of eye related side effects.[22]

The most common side effects in clinical trials were conjunctival haemorrhage, eye pain, vitreous floaters, increased intraocular pressure, and intraocular inflammation.

Although there is a theoretical risk for arterial thromboembolic events in people receiving VEGF-inhibitors by intravitreal injection, the observed incidence rate was low (< 4%) and similar to that seen with placebo.

Serious adverse events related to the injection procedure occurred with an incidence rate of less than 1% and included endophthalmitis, retinal detachment, and traumatic cataracts. Other serious ocular adverse events observed among ranibizumab-treated patients (incidence rate < 1%) included intraocular inflammation and blindness.[23]

Interactions

No significant interactions are known.[24]

Pharmacology

Ranibizumab is a monoclonal antibody that inhibits angiogenesis by inhibiting vascular endothelial growth factor A, a mechanism similar to that of Bevacizumab.[25]

Society and culture

Economics

Its effectiveness is similar to that of bevacizumab.[17][26] Its rates of side effects also appear similar.[21] However, ranibizumab typically costs $2,000 a dose, while the equivalent dose of bevacizumab typically costs $50.[27][28][29][30]

In November 2010, The New York Times reported that Genentech began offering secret rebates to about 300 ophthalmologists in an apparent inducement to get them to use more ranibizumab rather than their less expensive bevacizumab. This may have been in anticipation of the results of the CATT clinical trial,[28] which was sponsored by the National Eye Institute, and compared the relative safety and efficacy of ranibizumab and bevacizumab in treating AMD. In 2008, bevacizumab cost Medicare only $20 million for about 480,000 injections, while ranibizumab cost Medicare $537 million for only 337,000 injections.[31] A small study showed no superior effect of ranibizumab versus bevacizumab in direct comparison.[32] The initial results of the larger Comparison of Age-related Macular Degeneration Treatments Trials (CATT) trial were published in the New England Journal of Medicine in May 2011.[28] The trial showed that the two drugs "had equivalent effects on visual acuity when administered according to the same schedule;" however, serious adverse events were more common in the bevacizumab arm of the trial.

The results of several subsequent head-to-head trials of the two anti-VEGF treatments were later published, and the overall results reinforced CATT's findings. The two therapies performed equally at restoring visual acuity according to a 2012 meta-analysis,[33] and also in the IVAN trial, alone and in the investigators' meta-analysis pooling its own results with CATT's.[34] A 2012 meta-analysis focused specifically on safety issues concluded that the rates of several adverse events were higher with bevacizumab, although the absolute rates of ocular serious adverse events were low with both therapies: ocular adverse events were about 2.8 times as frequent with bevacizumab than with ranibizumab, and "The proportion of patients with serious infections and gastrointestinal disorders was also higher." The authors concluded that "clinicians and patients should continue to carefully weigh-up the benefits and harms when choosing between the two treatment options. We also emphasize the need for studies that are powered not just for efficacy, but for defined safety outcomes based on the signals detected in this systematic review".[26]

Biosimilars

Byooviz was approved for medical use in the European Union in August 2021.[9][35]

Ranibizumab-nuna (Byooviz) was approved for medical use in the United States in September 2021.[5][15]

Susvimo was approved for medical use in the United States in October 2021.[6][36]

In India, Lupin Limited received marketing approval for its biosimilar of Ranibizumab.[37]

In June 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 Ranivisio, intended for the treatment of neovascular (wet) age-related macular degeneration, visual impairment due to macular edema or choroidal neovascularization, and proliferative diabetic retinopathy.[38] The applicant for this medicinal product is Midas Pharma GmbH.[38] Ranivisio was approved for medical use in the European Union in August 2022.[10][39]

Ranibizumab-eqrn (CIMERLI®) was approved for medical use in the United States in August 2022.[7][40]

In September 2022, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Ximluci, intended for the treatment of neovascular (wet) age-related macular degeneration, visual impairment due to diabetic macular edema, proliferative diabetic retinopathy, visual impairment due to macular edema secondary to retinal vein occlusion (branch RVO or central RVO), and visual impairment due to choroidal neovascularization.[41] The applicant for this medicinal product is STADA Arzneimittel AG.[41] Ximluci was approved for medical use in the European Union in November 2022.[11][42]

In November 2023, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Rimmyrah, intended for the treatment of neovascular (wet) age-related macular degeneration, visual impairment due to diabetic macular edema, proliferative diabetic retinopathy, visual impairment due to macular edema secondary to retinal vein occlusion (branch RVO or central RVO), and visual impairment due to choroidal neovascularization.[43] The applicant for this medicinal product is QILU PHARMA SPAIN S.L.[43] Rimmyrah is a biosimilar medicinal product that is highly similar to the reference product Lucentis (ranibizumab), which was authorized in the EU in January 2007.[43]

In January 2024, Sandoz signed an agreement to acquire ranibizumab-eqrn, the biosimilar version of ranibizumab branded as CIMERLI®* from Coherus BioSciences, Inc. for an upfront cash purchase payment of USD 170 million.[44][45][46]

References

  1. ↑ 1.0 1.1 "AusPAR: Ranibizumab". 9 December 2014. https://www.tga.gov.au/auspar/auspar-ranibizumab-1. 
  2. ↑ 2.0 2.1 https://www.tga.gov.au/resources/auspmd/byooviz [bare URL]
  3. ↑ "Summary Basis of Decision - Byooviz". 12 August 2022. https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00598&lang=en. 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 "Lucentis- ranibizumab injection, solution". https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de4e66cc-ca05-4dc9-8262-e00e9b41c36d. 
  5. ↑ 5.0 5.1 5.2 5.3 "Byooviz Nuna- ranibizumab injection, solution". 27 April 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e46db299-edd1-4457-89b2-c1e2e505f1b0. 
  6. ↑ 6.0 6.1 6.2 "Susvimo- ranibizumab injection, solution". https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9c6d9e2a-9a77-4d11-b692-de87cfde3444. 
  7. ↑ 7.0 7.1 7.2 7.3 "Cimerli- ranibizumab-eqrn injection, solution". 19 October 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e0e23118-1490-a554-e053-2995a90ab90c. 
  8. ↑ 8.0 8.1 "Lucentis EPAR". 17 September 2018. https://www.ema.europa.eu/en/medicines/human/EPAR/lucentis.  Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  9. ↑ 9.0 9.1 9.2 9.3 "Byooviz EPAR". 23 June 2021. https://www.ema.europa.eu/en/medicines/human/EPAR/byooviz.  Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  10. ↑ 10.0 10.1 10.2 10.3 "Ranivisio EPAR". 20 June 2022. https://www.ema.europa.eu/en/medicines/human/EPAR/ranivisio.  Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  11. ↑ 11.0 11.1 11.2 "Ximluci EPAR". 14 September 2022. https://www.ema.europa.eu/en/medicines/human/EPAR/ximluci.  Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  12. ↑ "Intravitreal Ranibizumab for Choroidal Neovascularization in Best's Vitelliform Macular Dystrophy in a 6-Year-Old Boy". Journal of Pediatric Ophthalmology and Strabismus 48 Online (6): e19–e22. March 2011. doi:10.3928/01913913-20110308-02. PMID 21417187. https://journals.healio.com/doi/abs/10.3928/01913913-20110308-02. Retrieved 1 October 2021. 
  13. ↑ 13.0 13.1 "Lucentis Fact Sheet". http://www.gene.com/gene/products/information/tgr/lucentis/factsheet.html. 
  14. ↑ 14.0 14.1 "Drug Approval Package: Lucentis (Ranibizumab) NDA #125156". 26 September 2006. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/125156s0000_LucentisTOC.cfm. 
  15. ↑ 15.0 15.1 "FDA Approves First Biosimilar to Treat Macular Degeneration Disease and Other Eye Conditions". U.S. Food and Drug Administration (FDA) (Press release). 20 September 2021. Archived from the original on 20 September 2021. Retrieved 20 September 2021. This article incorporates text from this source, which is in the public domain.
  16. ↑ "Age-Related Macular Degeneration: A Scientometric Analysis". Medical Hypothesis, Discovery & Innovation in Ophthalmology 4 (2): 39–49. 2015. PMID 26060829. 
  17. ↑ 17.0 17.1 "A clearer view of evidence in treating macular degeneration: off-label policies and independent research". The Cochrane Database of Systematic Reviews 9 (9): ED000090. September 2014. doi:10.1002/14651858.ED000090. PMID 25228121. 
  18. ↑ "Anti-vascular endothelial growth factor for neovascular age-related macular degeneration". The Cochrane Database of Systematic Reviews 8 (8): CD005139. August 2014. doi:10.1002/14651858.CD005139.pub3. PMID 25170575. 
  19. ↑ "Aflibercept for neovascular age-related macular degeneration". The Cochrane Database of Systematic Reviews 2016 (2): CD011346. February 2016. doi:10.1002/14651858.CD011346.pub2. PMID 26857947. 
  20. ↑ "Anti-vascular endothelial growth factor for diabetic macular oedema: a network meta-analysis". The Cochrane Database of Systematic Reviews 2018 (10): CD007419. October 2018. doi:10.1002/14651858.CD007419.pub6. PMID 30325017. 
  21. ↑ 21.0 21.1 21.2 21.3 "Systemic safety of bevacizumab versus ranibizumab for neovascular age-related macular degeneration". The Cochrane Database of Systematic Reviews 9 (9): CD011230. September 2014. doi:10.1002/14651858.CD011230.pub2. PMID 25220133. 
  22. ↑ "A safety review and meta-analyses of bevacizumab and ranibizumab: off-label versus goldstandard". PLOS ONE 7 (8): e42701. 2012. doi:10.1371/journal.pone.0042701. PMID 22880086. Bibcode: 2012PLoSO...742701S. 
  23. ↑ (in de) Austria-Codex (2009/2010 ed.). Vienna: Österreichischer Apothekerverlag. 2009. ISBN 978-3-85200-196-8. [page needed]
  24. ↑ Ranibizumab , Lexi-Drugs. Ranibizumab. Lexi-Comp, Inc.; 2007.
  25. ↑ "ranibizumab". http://reference.medscape.com/drug/lucentis-ranibizumab-343645#10. 
  26. ↑ 26.0 26.1 "A safety review and meta-analyses of bevacizumab and ranibizumab: off-label versus goldstandard". PLOS ONE 7 (8): e42701. 2012. doi:10.1371/journal.pone.0042701. PMID 22880086. Bibcode: 2012PLoSO...742701S. 
  27. ↑ "An effective eye drug is available for $50. But many doctors choose a $2,000 alternative.". The Washington Post. 7 December 2013. https://www.washingtonpost.com/business/economy/an-effective-eye-drug-is-available-for-50-but-many-doctors-choose-a-2000-alternative/2013/12/07/1a96628e-55e7-11e3-8304-caf30787c0a9_story.html?hpid=z1. 
  28. ↑ 28.0 28.1 28.2 "Ranibizumab and bevacizumab for neovascular age-related macular degeneration". The New England Journal of Medicine 364 (20): 1897–1908. May 2011. doi:10.1056/NEJMoa1102673. PMID 21526923. 
  29. ↑ "Switch From Lucentis to Avastin Could Save Medicare $18B". Medscape. 17 June 2014. http://www.medscape.com/viewarticle/826911_print. 
  30. ↑ "Switching to less expensive blindness drug could save medicare part B $18 billion over a ten-year period". Health Affairs 33 (6): 931–939. June 2014. doi:10.1377/hlthaff.2013.0832. PMID 24889941. 
  31. ↑ "Genentech Offers Secret Rebates for Eye Drug". The New York Times. 3 November 2010. https://www.nytimes.com/2010/11/04/business/04eye.html. 
  32. ↑ "Bevacizumab vs ranibizumab for age-related macular degeneration: 1-year outcomes of a prospective, double-masked randomised clinical trial". Eye 24 (11): 1708–1715. November 2010. doi:10.1038/eye.2010.147. PMID 20885427. 
  33. ↑ "Ranibizumab for age-related macular degeneration: a meta-analysis of dose effects and comparison with no anti-VEGF treatment and bevacizumab". Journal of Clinical Pharmacy and Therapeutics 39 (3): 234–239. June 2014. doi:10.1111/jcpt.12146. PMID 24635444. 
  34. ↑ "Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial". Lancet 382 (9900): 1258–1267. October 2013. doi:10.1016/S0140-6736(13)61501-9. PMID 23870813. 
  35. ↑ "Byooviz Product information". https://ec.europa.eu/health/documents/community-register/html/h1572.htm. 
  36. ↑ "Susvimo: FDA-Approved Drugs". https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761197. 
  37. ↑ "Lupin receives CDSCO committee approval for marketing ranibizumab". http://www.pharmabiz.com/NewsDetails.aspx?aid=139853&sid=1. 
  38. ↑ 38.0 38.1 "Ranivisio: Pending EC decision". 22 June 2022. https://www.ema.europa.eu/en/medicines/human/summaries-opinion/ranivisio.  Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  39. ↑ "Ranivisio Product information". https://ec.europa.eu/health/documents/community-register/html/h1673.htm. 
  40. ↑ "FDA Approves Coherus' Cimerli (ranibizumab-eqrn) as the First and Only Interchangeable Biosimilar to Lucentis for All Five Indications, with 12 Months of Interchangeability Exclusivity" (Press release). Coherus BioSciences. 2 August 2022. Archived from the original on 3 August 2022. Retrieved 2 August 2022 – via GlobeNewswire News Room.
  41. ↑ 41.0 41.1 "Ximluci: Pending EC decision". 15 September 2022. https://www.ema.europa.eu/en/medicines/human/summaries-opinion/ximluci.  Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  42. ↑ "Ximluci Product information". https://ec.europa.eu/health/documents/community-register/html/h1691.htm. 
  43. ↑ 43.0 43.1 43.2 "Rimmyrah: Pending EC decision". 10 November 2023. https://www.ema.europa.eu/en/medicines/human/summaries-opinion/rimmyrah.  Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  44. ↑ "FDA Approves Ranibizumab-eqrn Biosimilar, Interchangeable with Lucentis" (in en). 2022-08-03. https://www.pharmacytimes.com/view/fda-approves-ranibizumab-eqrn-biosimilar-interchangeable-with-lucentis. 
  45. ↑ "Error: no |title= specified when using {{Cite web}}". https://www.sandoz.com/sandoz-announces-agreement-acquire-cimerlir-business-coherus-strengthening-position-us-market/. 
  46. ↑ MarketScreener (2024-01-22). "Sandoz: acquisition of ophthalmology biosimilar -January 22, 2024 at 01:49 am EST | MarketScreener" (in en). https://www.marketscreener.com/quote/stock/SANDOZ-GROUP-AG-160016887/news/Sandoz-acquisition-of-ophthalmology-biosimilar-45782186/. 



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