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Atoltivimab/maftivimab/odesivimab

January 01, 1970

Atoltivimab/maftivimab/odesivimab, sold under the brand name Inmazeb, is a fixed-dose combination of three monoclonal antibodies for the treatment of Zaire ebolavirus (Ebola virus).[2] It contains atoltivimab, maftivimab, and odesivimab-ebgn and was developed by Regeneron Pharmaceuticals.[2]

Atoltivimab/maftivimab/odesivimab
Combination of
AtoltivimabMonoclonal antibody
MaftivimabMonoclonal antibody
OdesivimabMonoclonal antibody
Clinical data
Trade namesInmazeb
Other namesREGN-EB3
AHFS/Drugs.comMonograph
License data
Routes of
administration		Intravenous
ATC code
  • None
Legal status
Legal status
Identifiers
CAS Number
  • 2500649-90-9
KEGG
  • D11922

The most common side effects include fever, chills, tachycardia (fast heart rate), tachypnea (fast breathing), and vomiting; however, these are also common symptoms of Ebola virus infection.[2][3]

Atoltivimab/maftivimab/odesivimab is the first FDA-approved treatment for Zaire ebolavirus.[2] Atoltivimab/maftivimab/odesivimab was approved for medical use in the United States in October 2020.[2][4][5][3][6] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[7] It is on the World Health Organization's List of Essential Medicines.[8]

Medical uses edit

Atoltivimab/maftivimab/odesivimab is indicated for the treatment of infection caused by Zaire ebolavirus.[2]

Contraindications edit

People who receive atoltivimab/maftivimab/odesivimab should avoid the concurrent administration of a live vaccine due to the treatment's potential to inhibit replication of a live vaccine virus indicated for prevention of Ebola virus infection and possibly reduce the vaccine's efficacy.[2]

Pharmacology edit

Mechanism of action edit

 
Colorized scanning electron micrograph of Ebola virus particles (green)

Atoltivimab/maftivimab/odesivimab is a combination of Zaire ebolavirus glycoprotein-directed human monoclonal antibodies.[2] The three antibodies target the glycoprotein that is on the surface of the Ebola virus.[2] This glycoprotein normally attaches to the cell via a receptor and fuses the viral and host cell membranes allowing the virus to enter the cell.[2] The antibodies can bind to it simultaneously at three different locations and block attachment and entry of the virus.[2]

This combination drug targets the Zaire species of Ebola virus. The Sudan and Bundibugyo strains have also caused outbreaks, and it is unlikely that it would be effective against these strains.[9]

History edit

Early development edit

The 2014 Ebola outbreak killed more than 11,300 people. Regeneron used its VelociGene, VelocImmune and VelociMab antibody discovery and production technologies and coordinated with the U.S. government's Biomedical Advanced Research and Development Authority (BARDA).[10] The therapy was developed in six months and a Phase 1 trial in healthy humans was completed in 2015.[10]

PALM trial edit

During the 2018 Équateur province Ebola outbreak, a similar monoclonal antibody treatment, mAb114, was requested by the Democratic Republic of Congo (DRC) Ministry of Public Health. mAb114 was approved for compassionate use by the World Health Organization MEURI ethical protocol and at DRC ethics board. mAb114 was sent along with other therapeutic agents to the outbreak sites.[11][12][13] However, the outbreak came to a conclusion before any therapeutic agents were given to patients.[13]

Approximately one month following the conclusion of the Équateur province outbreak, a distinct outbreak was noted in Kivu in the DRC (2018–20 Kivu Ebola outbreak). Once again, mAb114 received approval for compassionate use by WHO MEURI and DRC ethic boards and has been given to many patients under these protocols.[13] In November 2018, the Pamoja Tulinde Maisha (PALM [together save lives]) open-label randomized clinical control trial was begun at multiple treatment units testing mAb114, REGN-EB3 and remdesivir to ZMapp. Despite the difficulty of running a clinical trial in a conflict zone, investigators have enrolled 681 patients towards their goal of 725.[citation needed]

This is the second largest outbreak with (as of January 2020) over 3,400 confirmed or probable cases, including more than 2,200 who have died.[14][15]

An interim analysis by the Data Safety and Monitoring Board (DSMB) of the first 499 patient found that mAb114 and REGN-EB3 were superior to the comparator ZMapp. Overall mortality of patients in the ZMapp and Remdesivir groups were 49% and 53% compared to 34% and 29% for mAb114 and REGN-EB3. When looking at patients who arrived early after disease symptoms appeared, survival was 89% for mAB114 and 94% for REGN-EB3. While the study was not powered to determine whether there is any difference between REGN-EB3 and mAb114, the survival difference between those two therapies and ZMapp was significant. This led to the DSMB halting the study and PALM investigators dropping the remdesivir and ZMapp arms from the clinical trial. All patients in the outbreak who elect to participate in the trial will now be given either mAb114 or REGN-EB3.[16][17][18][19]

In August 2019, Congolese health officials announced it was more effective compared to two other treatments being used at the time.[20][18][21]

Among patients treated with it, 34% died; the mortality rate improved if the drug was administered soon after infection, in a timely diagnosis – critical for those infected with diseases like Ebola that can cause sepsis and, eventually, multiple organ dysfunction syndrome, more quickly than other diseases.[22] The survival rate if the drug was administered shortly after the infection was 89%.[14]

Atoltivimab/maftivimab/odesivimab was evaluated in 382 adult and pediatric participants with confirmed Zaire ebolavirus infection in one clinical trial (the PALM trial) and as part of an expanded access program conducted in the Democratic Republic of the Congo (DRC) during an Ebola virus outbreak in 2018/2019.[2][3] In the PALM trial, the safety and efficacy of atoltivimab/maftivimab/odesivimab was evaluated in a multi-center, open-label, randomized controlled trial, in which 154 participants received atoltivimab/maftivimab/odesivimab (50 mg of each monoclonal antibody) intravenously as a single infusion, and 168 participants received an investigational control.[2] The trial enrolled pediatric and adult participants (including pregnant women) with Zaire ebolavirus infection.[3] All participants received standard, supportive care for the disease.[3] The participants and the health care providers knew which treatment was being given.[3] The primary efficacy endpoint was 28-day mortality.[2] The primary analysis population was all participants who were randomized and concurrently eligible to receive either atoltivimab/maftivimab/odesivimab or the investigational control during the same time period of the trial.[2] Of the 154 participants who received atoltivimab/maftivimab/odesivimab, 33.8% died after 28 days, compared to 51% of the 153 participants who received a control.[2] In the expanded access program, an additional 228 participants received atoltivimab/maftivimab/odesivimab.[2]

Regulatory status edit

The FDA granted the application of atoltivimab/maftivimab/odesivimab-ebgn orphan drug and breakthrough therapy designations.[2] The FDA granted the approval of Inmazeb to Regeneron Pharmaceuticals with an indication for the treatment of infection caused by Zaire ebolavirus in October 2020.[2][6]

The drug has also received orphan drug designation from the European Medicines Agency.[23]

References edit

  1. ^ "Inmazeb- atoltivimab, maftivimab, and odesivimab-ebgn injection, solution". DailyMed. Retrieved 17 January 2021.
  2. ^ a b c d e f g h i j k l m n o p q r s t "FDA Approves First Treatment for Ebola Virus". U.S. Food and Drug Administration (FDA) (Press release). 14 October 2020. Retrieved 14 October 2020.   This article incorporates text from this source, which is in the public domain.
  3. ^ a b c d e f "Drug Trials Snapshots: Inmazeb". U.S. Food and Drug Administration. 14 October 2020. Retrieved 23 October 2020.   This article incorporates text from this source, which is in the public domain.
  4. ^ "Regeneron's Antibody Cocktail REGN-EB3 (Inmazeb) is First FDA-Approved Treatment for Ebola (Zaire Ebolavirus)". Regeneron Pharmaceuticals Inc. (Press release). 14 October 2020. Retrieved 14 October 2020.
  5. ^ "Inmazeb: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 15 October 2020.
  6. ^ a b "Drug Approval Package: Inmazeb". U.S. Food and Drug Administration. 12 November 2020. Retrieved 23 December 2020.
  7. ^ "New Drug Therapy Approvals 2020". U.S. Food and Drug Administration (FDA). 31 December 2020. Retrieved 17 January 2021.
  8. ^ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
  9. ^ "Ebola Treatment Massively Cuts Death Rate, But It's No Cure". Futurity. 16 August 2019. Retrieved 7 November 2019.
  10. ^ a b Stahl N. "Making a Drug You Hope No One Will Ever Need Harnessing the Power of Technology for Good". Retrieved 6 November 2019.
  11. ^ Check Hayden E (May 2018). "Experimental drugs poised for use in Ebola outbreak". Nature. 557 (7706): 475–476. Bibcode:2018Natur.557..475C. doi:10.1038/d41586-018-05205-x. ISSN 0028-0836. PMID 29789732.
  12. ^ WHO: Consultation on Monitored Emergency Use of Unregistered and Investigational Interventions for Ebola virus Disease. https://www.who.int/emergencies/ebola/MEURI-Ebola.pdf
  13. ^ a b c "NIH VideoCast - CC Grand Rounds: Response to an Outbreak: Ebola Virus Monoclonal Antibody (mAb114) Rapid Clinical Development". videocast.nih.gov. 13 March 2019. Retrieved 9 August 2019.
  14. ^ a b "Two Ebola drugs show promise amid ongoing outbreak". Nature. Retrieved 6 November 2019.
  15. ^ . WHO. 23 January 2020. Archived from the original on 5 March 2020. Retrieved 28 January 2020.
  16. ^ Mole B (13 August 2019). "Two Ebola drugs boost survival rates, according to early trial data". Ars Technica. Retrieved 17 August 2019.
  17. ^ "Independent monitoring board recommends early termination of Ebola therapeutics trial in DRC because of favorable results with two of four candidates". National Institutes of Health (NIH). 12 August 2019. Retrieved 17 August 2019.
  18. ^ a b McNeil DG (12 August 2019). "A Cure for Ebola? Two New Treatments Prove Highly Effective in Congo". The New York Times. Retrieved 13 August 2019.
  19. ^ Kingsley-Hall A. "Congo's experimental mAb114 Ebola treatment appears successful: authorities | Central Africa". www.theafricareport.com. Retrieved 15 October 2018.
  20. ^ Dwyer C (27 November 2018). "Ebola Treatment Trials Launched In Democratic Republic Of The Congo Amid Outbreak". NPR.org. Retrieved 28 May 2019.
  21. ^ Molteni M (12 August 2019). "Ebola is Now Curable. Here's How The New Treatments Work". Wired. Retrieved 13 August 2019.
  22. ^ "'Ebola is Now a Disease We Can Treat.' How a Cure Emerged from a War Zone". MSN.
  23. ^ "Palm Ebola Clinical Trial Stopped Early As Regeneron's REGN-EB3 Therapy Shows Superiority to ZMAPP in Preventing Ebola Deaths". Regeneron. Retrieved 6 November 2019.

Further reading edit

  • Mulangu S, Dodd LE, Davey RT, Tshiani Mbaya O, Proschan M, Mukadi D, et al. (December 2019). "A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics". The New England Journal of Medicine. 381 (24): 2293–2303. doi:10.1056/NEJMoa1910993. PMC 10680050. PMID 31774950.
  • Sivapalasingam S, Kamal M, Slim R, Hosain R, Shao W, Stoltz R, et al. (August 2018). "Safety, pharmacokinetics, and immunogenicity of a co-formulated cocktail of three human monoclonal antibodies targeting Ebola virus glycoprotein in healthy adults: a randomised, first-in-human phase 1 study". The Lancet. Infectious Diseases. 18 (8): 884–893. doi:10.1016/S1473-3099(18)30397-9. PMID 29929783. S2CID 49345203.

External links edit

  • Clinical trial number NCT03719586 for "Investigational Therapeutics for the Treatment of People With Ebola Virus Disease" at ClinicalTrials.gov
  • "Making a Drug You Hope No One Will Ever Need". Regeneron Pharmaceuticals.

January 01, 1970
atoltivimab, maftivimab, odesivimab, sold, under, brand, name, inmazeb, fixed, dose, combination, three, monoclonal, antibodies, treatment, zaire, ebolavirus, ebola, virus, contains, atoltivimab, maftivimab, odesivimab, ebgn, developed, regeneron, pharmaceutic. Atoltivimab maftivimab odesivimab sold under the brand name Inmazeb is a fixed dose combination of three monoclonal antibodies for the treatment of Zaire ebolavirus Ebola virus 2 It contains atoltivimab maftivimab and odesivimab ebgn and was developed by Regeneron Pharmaceuticals 2 Atoltivimab maftivimab odesivimabCombination ofAtoltivimabMonoclonal antibodyMaftivimabMonoclonal antibodyOdesivimabMonoclonal antibodyClinical dataTrade namesInmazebOther namesREGN EB3AHFS Drugs comMonographLicense dataUS DailyMed InmazebRoutes ofadministrationIntravenousATC codeNoneLegal statusLegal statusUS only 1 2 IdentifiersCAS Number2500649 90 9KEGGD11922 The most common side effects include fever chills tachycardia fast heart rate tachypnea fast breathing and vomiting however these are also common symptoms of Ebola virus infection 2 3 Atoltivimab maftivimab odesivimab is the first FDA approved treatment for Zaire ebolavirus 2 Atoltivimab maftivimab odesivimab was approved for medical use in the United States in October 2020 2 4 5 3 6 The U S Food and Drug Administration FDA considers it to be a first in class medication 7 It is on the World Health Organization s List of Essential Medicines 8 Contents 1 Medical uses 2 Contraindications 3 Pharmacology 3 1 Mechanism of action 4 History 4 1 Early development 4 2 PALM trial 4 3 Regulatory status 5 References 6 Further reading 7 External linksMedical uses editAtoltivimab maftivimab odesivimab is indicated for the treatment of infection caused by Zaire ebolavirus 2 Contraindications editPeople who receive atoltivimab maftivimab odesivimab should avoid the concurrent administration of a live vaccine due to the treatment s potential to inhibit replication of a live vaccine virus indicated for prevention of Ebola virus infection and possibly reduce the vaccine s efficacy 2 Pharmacology editMechanism of action edit nbsp Colorized scanning electron micrograph of Ebola virus particles green Atoltivimab maftivimab odesivimab is a combination of Zaire ebolavirus glycoprotein directed human monoclonal antibodies 2 The three antibodies target the glycoprotein that is on the surface of the Ebola virus 2 This glycoprotein normally attaches to the cell via a receptor and fuses the viral and host cell membranes allowing the virus to enter the cell 2 The antibodies can bind to it simultaneously at three different locations and block attachment and entry of the virus 2 This combination drug targets the Zaire species of Ebola virus The Sudan and Bundibugyo strains have also caused outbreaks and it is unlikely that it would be effective against these strains 9 History editEarly development edit The 2014 Ebola outbreak killed more than 11 300 people Regeneron used its VelociGene VelocImmune and VelociMab antibody discovery and production technologies and coordinated with the U S government s Biomedical Advanced Research and Development Authority BARDA 10 The therapy was developed in six months and a Phase 1 trial in healthy humans was completed in 2015 10 PALM trial edit This section may require cleanup to meet Wikipedia s quality standards The specific problem is Merged from REGN EB3 needs a consistent time line Please help improve this section if you can March 2021 Learn how and when to remove this message During the 2018 Equateur province Ebola outbreak a similar monoclonal antibody treatment mAb114 was requested by the Democratic Republic of Congo DRC Ministry of Public Health mAb114 was approved for compassionate use by the World Health Organization MEURI ethical protocol and at DRC ethics board mAb114 was sent along with other therapeutic agents to the outbreak sites 11 12 13 However the outbreak came to a conclusion before any therapeutic agents were given to patients 13 Approximately one month following the conclusion of the Equateur province outbreak a distinct outbreak was noted in Kivu in the DRC 2018 20 Kivu Ebola outbreak Once again mAb114 received approval for compassionate use by WHO MEURI and DRC ethic boards and has been given to many patients under these protocols 13 In November 2018 the Pamoja Tulinde Maisha PALM together save lives open label randomized clinical control trial was begun at multiple treatment units testing mAb114 REGN EB3 and remdesivir to ZMapp Despite the difficulty of running a clinical trial in a conflict zone investigators have enrolled 681 patients towards their goal of 725 citation needed This is the second largest outbreak with as of January 2020 over 3 400 confirmed or probable cases including more than 2 200 who have died 14 15 An interim analysis by the Data Safety and Monitoring Board DSMB of the first 499 patient found that mAb114 and REGN EB3 were superior to the comparator ZMapp Overall mortality of patients in the ZMapp and Remdesivir groups were 49 and 53 compared to 34 and 29 for mAb114 and REGN EB3 When looking at patients who arrived early after disease symptoms appeared survival was 89 for mAB114 and 94 for REGN EB3 While the study was not powered to determine whether there is any difference between REGN EB3 and mAb114 the survival difference between those two therapies and ZMapp was significant This led to the DSMB halting the study and PALM investigators dropping the remdesivir and ZMapp arms from the clinical trial All patients in the outbreak who elect to participate in the trial will now be given either mAb114 or REGN EB3 16 17 18 19 In August 2019 Congolese health officials announced it was more effective compared to two other treatments being used at the time 20 18 21 Among patients treated with it 34 died the mortality rate improved if the drug was administered soon after infection in a timely diagnosis critical for those infected with diseases like Ebola that can cause sepsis and eventually multiple organ dysfunction syndrome more quickly than other diseases 22 The survival rate if the drug was administered shortly after the infection was 89 14 Atoltivimab maftivimab odesivimab was evaluated in 382 adult and pediatric participants with confirmed Zaire ebolavirus infection in one clinical trial the PALM trial and as part of an expanded access program conducted in the Democratic Republic of the Congo DRC during an Ebola virus outbreak in 2018 2019 2 3 In the PALM trial the safety and efficacy of atoltivimab maftivimab odesivimab was evaluated in a multi center open label randomized controlled trial in which 154 participants received atoltivimab maftivimab odesivimab 50 mg of each monoclonal antibody intravenously as a single infusion and 168 participants received an investigational control 2 The trial enrolled pediatric and adult participants including pregnant women with Zaire ebolavirus infection 3 All participants received standard supportive care for the disease 3 The participants and the health care providers knew which treatment was being given 3 The primary efficacy endpoint was 28 day mortality 2 The primary analysis population was all participants who were randomized and concurrently eligible to receive either atoltivimab maftivimab odesivimab or the investigational control during the same time period of the trial 2 Of the 154 participants who received atoltivimab maftivimab odesivimab 33 8 died after 28 days compared to 51 of the 153 participants who received a control 2 In the expanded access program an additional 228 participants received atoltivimab maftivimab odesivimab 2 Regulatory status edit The FDA granted the application of atoltivimab maftivimab odesivimab ebgn orphan drug and breakthrough therapy designations 2 The FDA granted the approval of Inmazeb to Regeneron Pharmaceuticals with an indication for the treatment of infection caused by Zaire ebolavirus in October 2020 2 6 The drug has also received orphan drug designation from the European Medicines Agency 23 References edit Inmazeb atoltivimab maftivimab and odesivimab ebgn injection solution DailyMed Retrieved 17 January 2021 a b c d e f g h i j k l m n o p q r s t FDA Approves First Treatment for Ebola Virus U S Food and Drug Administration FDA Press release 14 October 2020 Retrieved 14 October 2020 nbsp This article incorporates text from this source which is in the public domain a b c d e f Drug Trials Snapshots Inmazeb U S Food and Drug Administration 14 October 2020 Retrieved 23 October 2020 nbsp This article incorporates text from this source which is in the public domain Regeneron s Antibody Cocktail REGN EB3 Inmazeb is First FDA Approved Treatment for Ebola Zaire Ebolavirus Regeneron Pharmaceuticals Inc Press release 14 October 2020 Retrieved 14 October 2020 Inmazeb FDA Approved Drugs U S Food and Drug Administration FDA Retrieved 15 October 2020 a b Drug Approval Package Inmazeb U S Food and Drug Administration 12 November 2020 Retrieved 23 December 2020 New Drug Therapy Approvals 2020 U S Food and Drug Administration FDA 31 December 2020 Retrieved 17 January 2021 World Health Organization 2023 The selection and use of essential medicines 2023 web annex A World Health Organization model list of essential medicines 23rd list 2023 Geneva World Health Organization hdl 10665 371090 WHO MHP HPS EML 2023 02 Ebola Treatment Massively Cuts Death Rate But It s No Cure Futurity 16 August 2019 Retrieved 7 November 2019 a b Stahl N Making a Drug You Hope No One Will Ever Need Harnessing the Power of Technology for Good Retrieved 6 November 2019 Check Hayden E May 2018 Experimental drugs poised for use in Ebola outbreak Nature 557 7706 475 476 Bibcode 2018Natur 557 475C doi 10 1038 d41586 018 05205 x ISSN 0028 0836 PMID 29789732 WHO Consultation on Monitored Emergency Use of Unregistered and Investigational Interventions for Ebola virus Disease https www who int emergencies ebola MEURI Ebola pdf a b c NIH VideoCast CC Grand Rounds Response to an Outbreak Ebola Virus Monoclonal Antibody mAb114 Rapid Clinical Development videocast nih gov 13 March 2019 Retrieved 9 August 2019 a b Two Ebola drugs show promise amid ongoing outbreak Nature Retrieved 6 November 2019 Ebola virus disease Democratic Republic of the Congo WHO 23 January 2020 Archived from the original on 5 March 2020 Retrieved 28 January 2020 Mole B 13 August 2019 Two Ebola drugs boost survival rates according to early trial data Ars Technica Retrieved 17 August 2019 Independent monitoring board recommends early termination of Ebola therapeutics trial in DRC because of favorable results with two of four candidates National Institutes of Health NIH 12 August 2019 Retrieved 17 August 2019 a b McNeil DG 12 August 2019 A Cure for Ebola Two New Treatments Prove Highly Effective in Congo The New York Times Retrieved 13 August 2019 Kingsley Hall A Congo s experimental mAb114 Ebola treatment appears successful authorities Central Africa www theafricareport com Retrieved 15 October 2018 Dwyer C 27 November 2018 Ebola Treatment Trials Launched In Democratic Republic Of The Congo Amid Outbreak NPR org Retrieved 28 May 2019 Molteni M 12 August 2019 Ebola is Now Curable Here s How The New Treatments Work Wired Retrieved 13 August 2019 Ebola is Now a Disease We Can Treat How a Cure Emerged from a War Zone MSN Palm Ebola Clinical Trial Stopped Early As Regeneron s REGN EB3 Therapy Shows Superiority to ZMAPP in Preventing Ebola Deaths Regeneron Retrieved 6 November 2019 Further reading editMulangu S Dodd LE Davey RT Tshiani Mbaya O Proschan M Mukadi D et al December 2019 A Randomized Controlled Trial of Ebola Virus Disease Therapeutics The New England Journal of Medicine 381 24 2293 2303 doi 10 1056 NEJMoa1910993 PMC 10680050 PMID 31774950 Sivapalasingam S Kamal M Slim R Hosain R Shao W Stoltz R et al August 2018 Safety pharmacokinetics and immunogenicity of a co formulated cocktail of three human monoclonal antibodies targeting Ebola virus glycoprotein in healthy adults a randomised first in human phase 1 study The Lancet Infectious Diseases 18 8 884 893 doi 10 1016 S1473 3099 18 30397 9 PMID 29929783 S2CID 49345203 External links editClinical trial number NCT03719586 for Investigational Therapeutics for the Treatment of People With Ebola Virus Disease at ClinicalTrials gov Making a Drug You Hope No One Will Ever Need Regeneron Pharmaceuticals Portals nbsp Medicine nbsp Viruses Retrieved from https en wikipedia org w index php title Atoltivimab maftivimab odesivimab amp oldid 1199346771, wikipedia, wiki, book, books, library,

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