Casirivimab/imdevimab

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Casirivimab/imdevimab
REGN-COV2 binding SARS-CoV-2 spike protein.png
REGN10933 (blue) and REGN10987 (orange) bound to SARS-CoV-2 spike protein (pink). From PDB: 6VSB, 6XDG​.
Combination of
CasirivimabMonoclonal antibody against spike protein of SARS-CoV-2
ImdevimabMonoclonal antibody against spike protein of SARS-CoV-2
Clinical data
Trade namesREGEN-COV, Ronapreve
AHFS/Drugs.comMonograph
License data
Pregnancy
category
Routes of
administration
Intravenous, subcutaneous injection
ATC code
  • None
Legal status
Legal status
Identifiers
DrugBank
KEGG
Casirivimab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetSpike protein of SARS-CoV-2
Clinical data
Other namesREGN10933
ATC code
  • None
Identifiers
CAS Number
  • 2415933-42-3
DrugBank
UNII
KEGG
Imdevimab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetSpike protein of SARS-CoV-2
Clinical data
Other namesREGN10987
ATC code
  • None
Identifiers
CAS Number
  • 2415933-40-1
DrugBank
UNII
KEGG

Casirivimab/imdevimab, sold under the brand name REGEN-COV among others,[5][7] is a combination medicine used for the treatment and prevention of COVID-19.[7] It consists of two human monoclonal antibodies, casirivimab and imdevimab that must be mixed together and administered as an infusion or subcutaneous injection.[9][5][7] The combination of two antibodies is intended to prevent mutational escape.[10] It is also available as a co-formulated product.[9] It was developed by the American biotechnology company Regeneron Pharmaceuticals.[11][12]

The most common side effects include allergic reactions, which include infusion related reactions, injection site reactions,[7] brief pain, weakness and others.[13]

The combination is approved under the brand name Ronapreve for medical use in Japan, the United Kingdom, the European Union, and Australia.[1][4][7][8][14][15]

Medical uses[edit]

In the European Union, the combination is indicated for the treatment of COVID-19 in people aged twelve years of age and older weighing at least 40 kilograms (88 lb) who do not require supplemental oxygen and who are at high increased risk of progressing to severe COVID-19;[7] and for the prevention of COVID-19 in people aged twelve years of age and older weighing at least 40 kilograms (88 lb).[7]

Trials[edit]

In a clinical trial of people with COVID-19, casirivimab and imdevimab, administered together, were shown to reduce COVID-19-related hospitalization or emergency room visits in people at high risk for disease progression within 28 days after treatment when compared to placebo.[6] The safety and effectiveness of this investigational therapy for use in the treatment of COVID-19 continues to be evaluated.[6]

The data supporting the emergency use authorization (EUA) for casirivimab and imdevimab are based on a randomized, double-blind, placebo-controlled clinical trial in 799 non-hospitalized adults with mild to moderate COVID-19 symptoms.[6] Of these participants, 266 received a single intravenous infusion of 2,400 milligrams casirivimab and imdevimab (1,200 mg of each), 267 received 8,000 mg casirivimab and imdevimab (4,000 mg of each), and 266 received a placebo, within three days of obtaining a positive SARS-CoV-2 viral test.[6]

The prespecified primary endpoint for the trial was time-weighted average change in viral load from baseline.[6] Viral load reduction in participants treated with casirivimab and imdevimab was larger than in participants treated with placebo at day seven.[6] However, the most important evidence that casirivimab and imdevimab administered together may be effective came from the predefined secondary endpoint of medically attended visits related to COVID-19, particularly hospitalizations and emergency room visits within 28 days after treatment.[6] For participants at high risk for disease progression, hospitalizations and emergency room visits occurred in 3% of casirivimab and imdevimab-treated participants on average compared to 9% in placebo-treated participants.[6] The effects on viral load, reduction in hospitalizations and ER visits were similar in participants receiving either of the two casirivimab and imdevimab doses.[6]

Since September 2020, REGEN-COV is being evaluated as part of the RECOVERY Trial,[16] and in June 2021 the first results of the research were announced with evidence proving the effectiveness of the treatment.

Deployment[edit]

REGEN-COV is manufactured at the Regeneron's manufacturing facility in Rensselaer, New York.[17] In September 2020, to free up manufacturing capacity for REGEN-COV, Regeneron began to shift production of its existing products from Rensselaer to the Irish city of Limerick.[18]

Regeneron has a deal in place with Roche (Genentech)[19] to manufacture and market REGEN-COV outside the United States.[20][21]

Society and culture[edit]

On 2 October 2020, Regeneron Pharmaceuticals announced that then-US President Donald Trump had received "a single 8 gram dose of REGN-COV2" after testing positive for SARS-CoV-2.[22][23] The drug was provided by the company in response to a "compassionate use" (temporary authorization for use) request from the president's physicians.[22]

In August 2021, Texas Governor Greg Abbott received REGEN-COV after testing positive for COVID-19.[24]

Economics[edit]

On 12 January 2021, the United States government agreed to purchase 1.25 million doses of the drug for $2.625 billion, at $2,100 per dose.[25][26] On 14 September, another 1.4 million doses were purchased for the same price, totaling $2.94 billion.[27]

On 24 January, the German government purchased 200,000 doses for €400 million at €2,000 per dose.[28]

On 25 May, Roche India and Cipla announced that the medicine would be available in India for Rs 59,750 per dose.[29]

On 24 September, the World Health Organization urged producers and governments to address the drug's high cost and called for technology sharing to enable the manufacture of biosimilar versions. The WHO also said that Unitaid is negotiating with Roche for lower prices and equitable distribution, especially in low- and middle income countries.[30]

Legal status[edit]

In November 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended granting a marketing authorization in the European Union for casirivimab/imdevimab (Ronapreve) for the treatment and prevention of COVID-19.[31][32] The company that applied for authorization of Ronapreve is Roche Registration GmbH.[32] Casirivimab/imdevimab was approved for medical use in the European Union in November 2021.[7]

Research[edit]

COVID-19[edit]

On 21 November 2020, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for casirivimab and imdevimab to be administered together for the treatment of mild to moderate COVID-19 in people twelve years of age or older weighing at least 40 kilograms (88 lb) with positive results of direct SARS-CoV-2 viral testing and who are at high risk for progressing to severe COVID-19.[6][20][9][33] This includes those who are 65 years of age or older or who have certain chronic medical conditions.[6] Casirivimab and imdevimab must be administered together by intravenous (IV) infusion or subcutaneous injection.[6][9]

Casirivimab and imdevimab are not authorized for people who are hospitalized due to COVID-19 or require oxygen therapy due to COVID-19.[6] A benefit of casirivimab and imdevimab treatment has not been shown in people hospitalized due to COVID-19.[6] Monoclonal antibodies, such as casirivimab and imdevimab, may be associated with worse clinical outcomes when administered to hospitalized people with COVID-19 requiring high flow oxygen or mechanical ventilation.[6] In June 2021, the EUA was revised to authorize "the use of the unapproved product, REGEN-COV (casirivimab and imdevimab) co-formulated product and REGEN-COV (casirivimab and imdevimab) supplied as individual vials to be administered together, for the treatment of mild to moderate COVID-19 in people aged twelve years of age and older weighing at least 40 kilograms (88 lb) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death."[9][5]

The EUA was issued to Regeneron Pharmaceuticals Inc.[6][20][33][34]

On 1 February 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) started a rolling review of data on the REGN‑COV2 antibody combination (casirivimab/imdevimab), which is being co-developed by Regeneron Pharmaceuticals, Inc. and F. Hoffman-La Roche, Ltd (Roche) for the treatment and prevention of COVID‑19.[35][36] In February 2021, the CHMP concluded that the combination, also known as REGN-COV2, can be used for the treatment of confirmed COVID-19 in people who do not require supplemental oxygen and who are at high risk of progressing to severe COVID-19.[37]

The Central Drugs Standards Control Organisation (CDSCO) in India, on 5 May 2021, granted an Emergency Use Authorization to Roche (Genentech)[19] and Regeneron[38] for use of the casirivimab/imdevimab cocktail in the country. The announcement came in light of the second wave of the COVID-19 pandemic in India. Roche India maintains partnership with Cipla, thereby permitting the latter to market the drug in the country.[39]

In July 2021, the U.S. FDA revised the emergency use authorization (EUA) for REGEN-COV (casirivimab and imdevimab, administered together) authorizing REGEN-COV for emergency use as post-exposure prophylaxis (prevention) for COVID-19 in people aged twelve years of age and older weighing at least 40 kilograms (88 lb) who are at high risk for progression to severe COVID-19, including hospitalization or death.[40] REGEN-COV remains authorized for the treatment of mild-to-moderate COVID-19 in people aged twelve years of age and older weighing at least 40 kilograms (88 lb) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.[40]

On 12 April 2021, Roche (Genentech)[19] and Regeneron announced that the Phase III clinical trial REGN-COV 2069 met both primary and secondary endpoints, reducing risk of infection by 81% for the non-infected participants, and reducing time-to-resolution of symptoms for symptomatic participants to one week vs. three weeks in the placebo group.[41]

On 16 June 2021, preliminary form the Recovery trial showed reduced mortality from 30% to 24% in patients that had produced no antibodies themselves which were 33% of the total of participants.[42][43][44][45]

References[edit]

  1. ^ a b c "Ronapreve". Therapeutic Goods Administration (TGA). 18 October 2021. Retrieved 22 October 2021.
  2. ^ "COVID-19 treatment: Roche Products Pty Ltd, casirivimab + imdevimab (Ronapreve)". Therapeutic Goods Administration (TGA). 15 October 2021. Retrieved 22 October 2021.
  3. ^ "Casirivimab (casirivimab) and imdevimab (imdevimab)". Government of Canada. Retrieved 20 December 2021.
  4. ^ a b "Summary of Product Characteristics for Ronapreve". Medicines and Healthcare products Regulatory Agency (MHRA). 20 August 2021. Retrieved 29 August 2021.
  5. ^ a b c d "Casirivimab injection, solution, concentrate Imdevimab injection, solution, concentrate REGEN-COV – casirivimab and imdevimab kit". DailyMed. Retrieved 18 March 2021.
  6. ^ a b c d e f g h i j k l m n o p q "Coronavirus (COVID-19) Update: FDA Authorizes Monoclonal Antibodies for Treatment of COVID-19". U.S. Food and Drug Administration (FDA) (Press release). 21 November 2020. Retrieved 21 November 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  7. ^ a b c d e f g h i "Ronapreve EPAR". European Medicines Agency. Retrieved 12 November 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  8. ^ a b "Japan becomes first country to approve Ronapreve (casirivimab and imdevimab) for the treatment of mild to moderate COVID-19". Roche (Press release). 20 July 2021. Retrieved 29 August 2021.
  9. ^ a b c d e "Fact Sheet For Health Care Providers Emergency Use Authorization (EUA) Of Casirivimab And Imdevimab" (PDF). U.S. Food and Drug Administration (FDA). June 2021.
  10. ^ Baum A, Fulton BO, Wloga E, Copin R, Pascal KE, Russo V, et al. (August 2020). "Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies". Science. 369 (6506): 1014–1018. Bibcode:2020Sci...369.1014B. doi:10.1126/science.abd0831. PMC 7299283. PMID 32540904.
  11. ^ Kelland K (14 September 2020). "Regeneron's antibody drug added to UK Recovery trial of COVID treatments". Reuters. Retrieved 14 September 2020.
  12. ^ "Regeneron's COVID-19 Response Efforts". Regeneron Pharmaceuticals. Retrieved 14 September 2020.
  13. ^ Affairs (ASPA), Assistant Secretary for Public (7 January 2021). "Monoclonal Antibodies for High-Risk COVID-19 Positive Patients". combatCOVID.hhs.gov. Retrieved 29 December 2021.
  14. ^ "Regulatory approval of Ronapreve". Medicines and Healthcare products Regulatory Agency (MHRA). 20 August 2021. Retrieved 29 August 2021.
  15. ^ "First monoclonal antibody treatment for COVID-19 approved for use in the UK" (Press release). Medicines and Healthcare products Regulatory Agency (MHRA). 20 August 2021. Retrieved 29 August 2021.
  16. ^ "RECOVERY COVID-19 phase 3 trial to evaluate Regeneron's REGN-COV2 investigational antibody cocktail in the UK". Recovery Trial. 14 September 2020.
  17. ^ Williams, Stephen (3 October 2020). "Experimental drug given to President made locally". The Daily Gazette.
  18. ^ Stanton, Dan (11 September 2020). "Manufacturing shift to Ireland frees up US capacity for Regeneron's COVID antibodies". BioProcess International.
  19. ^ a b c "Genentech and Regeneron Collaborate to Significantly Increase Global Supply of REGN-COV2 Investigational Antibody Combination for COVID-19" (Press release). Genentech. 19 August 2020. Retrieved 8 June 2021 – via Business Wire.
  20. ^ a b c "Regeneron Reports Positive Interim Data with REGEN-COV Antibody Cocktail used as Passive Vaccine to Prevent COVID-19" (Press release). Regeneron Pharmaceuticals. 26 January 2021. Retrieved 19 March 2021 – via PR Newswire.
  21. ^ "Roche and Regeneron link up on a coronavirus antibody cocktail". CNBC. 19 August 2020. Retrieved 14 September 2020.
  22. ^ a b Thomas K (2 October 2020). "President Trump Received Experimental Antibody Treatment". The New York Times. ISSN 0362-4331. Retrieved 2 October 2020.
  23. ^ Hackett DW (3 October 2020). "8-Gram Dose of COVID-19 Antibody Cocktail Provided to President Trump". www.precisionvaccinations.com. Archived from the original on 3 October 2020.
  24. ^ Schneider A (17 August 2021). "Texas Gov. Greg Abbott Tests Positive For The Coronavirus". NPR. Retrieved 17 August 2021.
  25. ^ "U.S. to buy 1.25 million additional doses of Regeneron's COVID-19 antibody cocktail". Reuters. 12 January 2021. Retrieved 30 September 2021.
  26. ^ "Regeneron announces U.S. government agreement to purchase additional COVID-19 antibody cocktail doses" (Press release). Tarrytown, New York: Regeneron. 12 January 2021. Retrieved 30 September 2021.
  27. ^ "U.S. to buy 1.4 mln additional doses of Regeneron's COVID-19 therapy". Reuters. 14 September 2021. Retrieved 30 September 2021.
  28. ^ "Coronavirus: Germany to use new antibody-based drug". DW. 24 January 2021. Retrieved 30 September 2021.
  29. ^ "Roche's Antibody Cocktail launched in India at Rs 59,750/dose". The Indian Express. 25 May 2021. Retrieved 30 September 2021.
  30. ^ "On new recommendation for treatment of COVID-19 patients: WHO calls for equitable access to casirivimab and imdevimab for COVID-19". World Health Organization. 24 September 2021. Retrieved 30 September 2021.
  31. ^ "Ronapreve: Pending EC decision". European Medicines Agency (EMA). 11 November 2021. Retrieved 11 November 2021.
  32. ^ a b "COVID-19: EMA recommends authorisation of two monoclonal antibody medicines". European Medicines Agency (EMA) (Press release). 11 November 2021. Retrieved 11 November 2021.
  33. ^ a b "Casirivimab And Imdevimab Emergency Use Authorization (EUA)" (PDF). U.S. Food and Drug Administration (FDA). July 2021.
  34. ^ "Casirivimab and Imdevimab". Regeneron Pharmaceuticals. Retrieved 19 March 2021.
  35. ^ "EMA starts rolling review of REGN‑COV2 antibody combination (casirivimab / imdevimab)" (Press release). European Medicines Agency (EMA). 1 February 2021. Retrieved 1 February 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  36. ^ "EMA reviewing data on monoclonal antibody use for COVID-19" (Press release). European Medicines Agency (EMA). 4 February 2021. Retrieved 4 March 2021.
  37. ^ "EMA issues advice on use of REGN-COV2 antibody combination (casirivimab / imdevimab)" (Press release). European Medicines Agency (EMA). 26 February 2021. Retrieved 5 March 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  38. ^ "India approves Roche/Regeneron antibody cocktail to treat Covid-19 – India News". The Times of India. 5 May 2021. Retrieved 8 June 2021.
  39. ^ "Roche receives Emergency Use Authorisation in India for its investigational Antibody Cocktail (Casirivimab and Imdevimab) used in the treatment of Covid-19". Cipla. Retrieved 6 May 2021.
  40. ^ a b "FDA authorizes REGEN-COV monoclonal antibody therapy for post-exposure prophylaxis (prevention) for COVID-19". U.S. Food and Drug Administration (FDA). 30 July 2021. Retrieved 30 July 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  41. ^ "Phase III prevention trial showed subcutaneous administration of investigational antibody cocktail casirivimab and imdevimab reduced risk of symptomatic COVID-19 infections by 81%". streetinsider.com. 12 April 2021. Archived from the original on 12 April 2021. Retrieved 12 April 2021.
  42. ^ Kupferschmidt K (16 June 2021). "Monoclonal antibodies cut risk of dying from COVID-19 – but only in some patients". Science. doi:10.1126/science.abk0053 (inactive 31 October 2021). A paper with the results will be made available on the medRxiv preprint server later today, the researchers say.CS1 maint: DOI inactive as of October 2021 (link)
  43. ^ Group, RECOVERY Collaborative; Horby, Peter W.; Mafham, Marion; Peto, Leon; Campbell, Mark; Pessoa-Amorim, Guilherme; Spata, Enti; Staplin, Natalie; Emberson, Jonathan R.; Prudon, Benjamin; Hine, Paul (16 June 2021). "Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial": 2021.06.15.21258542. doi:10.1101/2021.06.15.21258542. S2CID 235444491. Cite journal requires |journal= (help)
  44. ^ "RECOVERY trial finds Regeneron's monoclonal antibody combination reduces deaths for hospitalised COVID-19 patients who have not mounted their own immune response — RECOVERY Trial". www.recoverytrial.net. Retrieved 4 October 2021.
  45. ^ "Another life-saving Covid treatment found". BBC News. 16 June 2021. Retrieved 4 October 2021.

Further reading[edit]

External links[edit]