Brincidofovir (CMX-001) for refractory and resistant CMV and HSV infections in immunocompromised cancer patients

A single-center experience

Danielle El-Haddad, Firas El Chaer, Jackapat Vanichanan, Dimpy P Shah, Ella J. Ariza-Heredia, Victor E. Mulanovich, Alison M. Gulbis, Elizabeth J. Shpall, Roy F. Chemaly

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background The emergence of resistance to available antiviral drugs may cause higher Cytomegalovirus (CMV)-associated morbidity and mortality in hematopoietic cell transplant (HCT) recipients. Few novel antiviral drugs are being developed with potential effect against refractory or resistant CMV infections. Brincidofovir, an oral nucleotide analog and prodrug of cidofovir, has shown in vitro activity against CMV. Methods We reviewed data of 4 cancer patients with resistant CMV or herpes simplex virus (HSV) infections and were treated with brincidofovir under emergency IND application. Results Three out of the 4 patients with resistant CMV or HSV infections responded to brincidofovir. Brincidofovir achieved virological response in 2 patients with confirmed UL97 mutation (ganciclovir-resistant CMV infection), but failed to control CMV when a specific UL54 mutation was present (conferring resistance to foscarnet and cidofovir), as seen with patient 3. Furthermore, brincidofovir was effective for treatment of acyclovir resistant HSV infection, as described in patient 4 which is in alignment with the high in vitro potency of brincidofovir (about 100-fold more than acyclovir) for inhibition of HSV replication. Only one patient had brincidofovir-related diarrhea without any evidence of concurrent gastrointestinal GVHD. Conclusion Without the nephrotoxicity of cidofovir, brincidofovir could be an effective alternative for CMV-resistant and HSV-resistant infections. Combination therapy of brincidofovir with other antiviral agent, at a conventional or a lower dose, could be considered to potentiate efficacy and minimize side effects of the approved antiviral agents.

Original languageEnglish (US)
Pages (from-to)58-62
Number of pages5
JournalAntiviral Research
Volume134
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

Fingerprint

Immunocompromised Host
Virus Diseases
Simplexvirus
Cytomegalovirus
Neoplasms
Antiviral Agents
Acyclovir
Cytomegalovirus Infections
Foscarnet
cidofovir hexadecyloxypropyl ester
Mutation
Ganciclovir
Prodrugs
Virus Replication
Diarrhea
Emergencies
Nucleotides
Morbidity
Transplants
Mortality

Keywords

  • Brincidofovir
  • Cancer
  • Cytomegalovirus
  • Herpes simplex virus
  • Resistance

ASJC Scopus subject areas

  • Pharmacology
  • Virology

Cite this

Brincidofovir (CMX-001) for refractory and resistant CMV and HSV infections in immunocompromised cancer patients : A single-center experience. / El-Haddad, Danielle; El Chaer, Firas; Vanichanan, Jackapat; Shah, Dimpy P; Ariza-Heredia, Ella J.; Mulanovich, Victor E.; Gulbis, Alison M.; Shpall, Elizabeth J.; Chemaly, Roy F.

In: Antiviral Research, Vol. 134, 01.10.2016, p. 58-62.

Research output: Contribution to journalArticle

El-Haddad, D, El Chaer, F, Vanichanan, J, Shah, DP, Ariza-Heredia, EJ, Mulanovich, VE, Gulbis, AM, Shpall, EJ & Chemaly, RF 2016, 'Brincidofovir (CMX-001) for refractory and resistant CMV and HSV infections in immunocompromised cancer patients: A single-center experience', Antiviral Research, vol. 134, pp. 58-62. https://doi.org/10.1016/j.antiviral.2016.08.024
El-Haddad, Danielle ; El Chaer, Firas ; Vanichanan, Jackapat ; Shah, Dimpy P ; Ariza-Heredia, Ella J. ; Mulanovich, Victor E. ; Gulbis, Alison M. ; Shpall, Elizabeth J. ; Chemaly, Roy F. / Brincidofovir (CMX-001) for refractory and resistant CMV and HSV infections in immunocompromised cancer patients : A single-center experience. In: Antiviral Research. 2016 ; Vol. 134. pp. 58-62.
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abstract = "Background The emergence of resistance to available antiviral drugs may cause higher Cytomegalovirus (CMV)-associated morbidity and mortality in hematopoietic cell transplant (HCT) recipients. Few novel antiviral drugs are being developed with potential effect against refractory or resistant CMV infections. Brincidofovir, an oral nucleotide analog and prodrug of cidofovir, has shown in vitro activity against CMV. Methods We reviewed data of 4 cancer patients with resistant CMV or herpes simplex virus (HSV) infections and were treated with brincidofovir under emergency IND application. Results Three out of the 4 patients with resistant CMV or HSV infections responded to brincidofovir. Brincidofovir achieved virological response in 2 patients with confirmed UL97 mutation (ganciclovir-resistant CMV infection), but failed to control CMV when a specific UL54 mutation was present (conferring resistance to foscarnet and cidofovir), as seen with patient 3. Furthermore, brincidofovir was effective for treatment of acyclovir resistant HSV infection, as described in patient 4 which is in alignment with the high in vitro potency of brincidofovir (about 100-fold more than acyclovir) for inhibition of HSV replication. Only one patient had brincidofovir-related diarrhea without any evidence of concurrent gastrointestinal GVHD. Conclusion Without the nephrotoxicity of cidofovir, brincidofovir could be an effective alternative for CMV-resistant and HSV-resistant infections. Combination therapy of brincidofovir with other antiviral agent, at a conventional or a lower dose, could be considered to potentiate efficacy and minimize side effects of the approved antiviral agents.",
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T1 - Brincidofovir (CMX-001) for refractory and resistant CMV and HSV infections in immunocompromised cancer patients

T2 - A single-center experience

AU - El-Haddad, Danielle

AU - El Chaer, Firas

AU - Vanichanan, Jackapat

AU - Shah, Dimpy P

AU - Ariza-Heredia, Ella J.

AU - Mulanovich, Victor E.

AU - Gulbis, Alison M.

AU - Shpall, Elizabeth J.

AU - Chemaly, Roy F.

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N2 - Background The emergence of resistance to available antiviral drugs may cause higher Cytomegalovirus (CMV)-associated morbidity and mortality in hematopoietic cell transplant (HCT) recipients. Few novel antiviral drugs are being developed with potential effect against refractory or resistant CMV infections. Brincidofovir, an oral nucleotide analog and prodrug of cidofovir, has shown in vitro activity against CMV. Methods We reviewed data of 4 cancer patients with resistant CMV or herpes simplex virus (HSV) infections and were treated with brincidofovir under emergency IND application. Results Three out of the 4 patients with resistant CMV or HSV infections responded to brincidofovir. Brincidofovir achieved virological response in 2 patients with confirmed UL97 mutation (ganciclovir-resistant CMV infection), but failed to control CMV when a specific UL54 mutation was present (conferring resistance to foscarnet and cidofovir), as seen with patient 3. Furthermore, brincidofovir was effective for treatment of acyclovir resistant HSV infection, as described in patient 4 which is in alignment with the high in vitro potency of brincidofovir (about 100-fold more than acyclovir) for inhibition of HSV replication. Only one patient had brincidofovir-related diarrhea without any evidence of concurrent gastrointestinal GVHD. Conclusion Without the nephrotoxicity of cidofovir, brincidofovir could be an effective alternative for CMV-resistant and HSV-resistant infections. Combination therapy of brincidofovir with other antiviral agent, at a conventional or a lower dose, could be considered to potentiate efficacy and minimize side effects of the approved antiviral agents.

AB - Background The emergence of resistance to available antiviral drugs may cause higher Cytomegalovirus (CMV)-associated morbidity and mortality in hematopoietic cell transplant (HCT) recipients. Few novel antiviral drugs are being developed with potential effect against refractory or resistant CMV infections. Brincidofovir, an oral nucleotide analog and prodrug of cidofovir, has shown in vitro activity against CMV. Methods We reviewed data of 4 cancer patients with resistant CMV or herpes simplex virus (HSV) infections and were treated with brincidofovir under emergency IND application. Results Three out of the 4 patients with resistant CMV or HSV infections responded to brincidofovir. Brincidofovir achieved virological response in 2 patients with confirmed UL97 mutation (ganciclovir-resistant CMV infection), but failed to control CMV when a specific UL54 mutation was present (conferring resistance to foscarnet and cidofovir), as seen with patient 3. Furthermore, brincidofovir was effective for treatment of acyclovir resistant HSV infection, as described in patient 4 which is in alignment with the high in vitro potency of brincidofovir (about 100-fold more than acyclovir) for inhibition of HSV replication. Only one patient had brincidofovir-related diarrhea without any evidence of concurrent gastrointestinal GVHD. Conclusion Without the nephrotoxicity of cidofovir, brincidofovir could be an effective alternative for CMV-resistant and HSV-resistant infections. Combination therapy of brincidofovir with other antiviral agent, at a conventional or a lower dose, could be considered to potentiate efficacy and minimize side effects of the approved antiviral agents.

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KW - Cytomegalovirus

KW - Herpes simplex virus

KW - Resistance

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