Brincidofovir

Brincidofovir
Clinical data
Legal status
Legal status
  • US: Investigational
Identifiers
CAS Number 444805-28-1
PubChem CID 483477
ChemSpider 424003
ChEMBL CHEMBL203321
Synonyms CMX001; Cidofovir-HDP; hexadecyloxypropyl-cidofovir
Chemical data
Formula C27H52N3O7P
Molar mass 561.70 g/mol

Brincidofovir (CMX001) is an experimental antiviral drug being developed by Chimerix of Durham, NC, for the treatment of cytomegalovirus, adenovirus, smallpox, and ebolavirus infections.[1] Brincidofovir is a prodrug of cidofovir.[2] Conjugated to a lipid, the compound is designed to release cidofovir intracellularly, allowing for higher intracellular and lower plasma concentrations of cidofovir, effectively increasing its activity against dsDNA viruses, as well as oral bioavailability.[3]

In animal trials the drug has shown activity against cytomegalovirus, adenoviruses, BK virus, smallpox, and herpes simplex viruses.[2][4] Preliminary in vitro tests have also shown it to have potential for the treatment of Ebola virus disease, which is somewhat paradoxical, as Ebola is not a DNA virus.[5]

Brincidofovir is currently in Phase III clinical trials for use in humans against cytomegalovirus and adenovirus, after testing for safety in over 1000 human subjects,[6] and has received FDA Fast Track Designation for treatment of cytomegalovirus, adenovirus, and smallpox.[7] On October 6, 2014, Chimerix received an FDA authorization for emergency investigational new drug applications of brincidofovir for the treatment of Ebola virus disease.

Brincidofovir was administered to the first patient diagnosed in the Ebola virus disease outbreak in the US in 2014.[7][8] The patient was given the drug starting six days after hospital admission when he was already critically ill; he died four days later.[9][10] Brincidofovir was also given to Ebola patient Ashoka Mukpo at the Nebraska Medical Center, who had developed the disease and then was pronounced Ebola-free and released from the Center on 22 October 2014.[11]

In October 2014, Chimerix reported it had been given approval by the FDA to start Phase 2 trials in patients infected with ebolaviruses for brincidofovir's safety, tolerability, and efficacy.[12] A trial commenced during January 2015 in Liberia,[13] but was subsequently discontinued. Because of a lack of suitable subjects in Liberia, Oxford University and Médecins Sans Frontières planned to extend the trial to Sierra Leone, where there were still Ebola cases; but on the 30th of January 2015, the manufacturer decided to withdraw support for the trial and end discussion of future trials.[14][15]

Ethical considerations

Brincidofovir (CMX001) was the subject of widespread social media campaigning which was then picked up by national news sources when a young boy with an adenovirus infection following a bone marrow transplant was denied compassionate use of the drug.[16] Chimerix quickly got permission to start a limited Phase III trial which allowed the use of the drug for this patient but also sparked a debate on the ethics of use of social media, the allocation of limited resources of a small company, and the emphasis on the individual over the group. The new use of the drug had the potential to interfere with the process to get the drug approved and widely marketed.

Brincidofovir is one of several experimental drugs administered to a small number of patients to treat Ebola virus disease during the 2014 outbreak. The WHO published a report on the ethics of using unregistered interventions to treat Ebola, where they concluded that "In the particular context of the current Ebola outbreak in West Africa, it is ethically acceptable to offer unproven interventions that have shown promising results in the laboratory and in animal models but have not yet been evaluated for safety and efficacy in humans as potential treatment or prevention."[17]

See also

References

  1. ↑ http://www.chimerix.com/c/discovery-clinical-trials/brincidofovir-ebola.php
  2. 1 2 "Brincidofovir (CMX001)". Chimerix.
  3. ↑ "Development of CMX001 (Brincidofovir) for the treatment of serious diseases or conditions caused by dsDNA viruses". Expert Rev Anti Infect Ther 12 (10): 1171–8. October 2014. doi:10.1586/14787210.2014.948847.
  4. ↑ Quenelle, Debra C.; Lampert, Bernhardt; Collins, Deborah J.; Rice, Terri L.; Painter, George R.; Kern, Earl R. (2010). "Efficacy of CMX001 against Herpes Simplex Virus Infections in Mice and Correlations with Drug Distribution Studies". The Journal of Infectious Diseases 202 (10): 1492–9. doi:10.1086/656717. PMC 2957530. PMID 20923374.
  5. ↑ David Kroll (7 October 2014). "Chimerix's Brincidofovir Given To Dallas, Nebraska Ebola Patients". forbes.com.
  6. ↑ "Brincidofovor for Ebola". Chimerix.
  7. 1 2 "Chimerix Announces Emergency Investigational New Drug Applications for Brincidofovir Authorized by FDA for Patients With Ebola Virus Disease". Retrieved 8 October 2014.
  8. ↑ "Dallas Ebola Patient Receives Experimental Drug". The Huffington Post. 6 October 2014. Retrieved 8 October 2014.
  9. ↑ "Thomas Duncan, the Texas Ebola patient, has died". Washington Post. Retrieved 8 October 2014.
  10. ↑ Dallas Ebola patient waited nearly a week for experimental drug; family claims bias
  11. ↑ "http://www.nbcnews.com/storyline/ebola-virus-outbreak/young-healthy-how-nbc-news-freelancer-ashoka-mukpo-survived-ebola-n231681". External link in |title= (help); "Ebola Patient Slightly Improved: Father "Cautiously Optimistic"". Nebraska Medical Center. 10 October 2014.
  12. ↑ Chimerix to Conduct Ebola Drug Trial: Drug Company Gets FDA Approval to Start Trial Immediately in Infected Patients
  13. ↑ "Trials of untested Ebola drugs begin in West Africa". Reuters. Retrieved 6 January 2015.
  14. ↑ "Chimerix Ends Brincidofovir Ebola Trials To Focus On Adenovirus And CMV". Forbes. Retrieved 31 January 2015.
  15. ↑ http://www.msf.org/article/ebola-drug-trial-liberia-halted
  16. ↑ Chimerix CEO Out In Wake Of Josh Hardy Compassionate Use Media Frenzy, Forbes, April 10, 2014
  17. ↑ "WHO - Ethical considerations for use of unregistered interventions for Ebola virus disease". Retrieved 8 October 2014.
This article is issued from Wikipedia - version of the Saturday, April 02, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.