Salvage Treatment of Refractory HSV Oral Lesions with Pritelivir in Allogeneic Hematopoietic Cell Transplant Recipients

Bosetti, Davide; Bernardi, Chiara; Maulini, M; Giannotti, Federica; Mamez, Anne‐Claire; Masouridi‐Levrat, Stavroula; Chalandon, Yves; Neofytos, Dionysios

doi:10.1128/aac.01732-22

Cited by 11 publications

(3 citation statements)

References 34 publications

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“…In 2023, it was additionally approved for recurrent herpes simplex. Pritelivir, a similar helicase‐primase complex inhibitor, is now currently developed, and it has been found to be effective against ACV‐resistant HSV‐1 infection after allo‐HSCT [ 5 ]. However, the efficacy of AMNV has not been elucidated, and this report first showed its efficacy and safety in this setting.…”

Section: Discussionmentioning

confidence: 99%

Successful treatment of acyclovir‐resistant herpes simplex virus infection with amenamevir in a patient who received umbilical cord blood transplantation for T‐cell prolymphocytic leukemia

Kawamura,

Uchibori,

Arakawa

et al. 2024

eJHaem

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A 34‐year‐old woman received umbilical cord blood transplantation for refractory T‐cell prolymphocytic leukemia after salvage therapy with alemtuzumab. She developed right angular cheilitis on the 46th day after transplantation, which worsened after receiving systemic steroid therapy for extensive chronic graft versus host disease. The treatment dosage of acyclovir (ACV), ganciclovir, and vidarabine ointment was not effective due to ACV‐resistant mutations of the herpes simplex virus type 1 (HSV‐1) in the thymidine kinase domain. Foscarnet is expected to be effective against ACV‐resistant HSV‐1 infection. However, it could not be used because the patient developed renal dysfunction. Several viral thymidine kinase mutations related to ACV resistance were found in the patient's sample. Nevertheless, amenamevir, a helicase‐primase complex inhibitor, was effective in our patient who was significantly immunocompromised after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). ACV‐resistant HSV infection after allo‐HSCT is an rare but important complication in the era of low‐dose long‐term ACV prophylaxis. To date, there is no established treatment against ACV‐resistant HSV infection. This case report showed that amenamevir could be a promising treatment option for ACV‐resistant HSV infection in patients with renal failure after allo‐HSCT.

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Section: Discussionmentioning

confidence: 99%

Successful treatment of acyclovir‐resistant herpes simplex virus infection with amenamevir in a patient who received umbilical cord blood transplantation for T‐cell prolymphocytic leukemia

Kawamura,

Uchibori,

Arakawa

et al. 2024

eJHaem

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“…Two new drugs targeting the helicase-primase complex in both HSV and VZV, and not requiring viral TK for activation, offer a possible solution [ 128 ]. Pritelivir and amenamevir seem to show promise as effective drugs in treating acute infection, with the former under clinical trial, though with various promising case reports, and the latter having been approved for use against VZV in Japan [ 129 , 130 , 131 ]. Pritelivir has been further shown to significantly reduce viral shedding in patients with frequent recurrences, with reports suggesting a much lower incidence of viral resistance, and has been proposed as an option to prevent recurrence in immunocompromised patients [ 128 , 132 , 133 ].…”

Section: Mucocutaneous Viral Infectionsmentioning

confidence: 99%

The Scope and Impact of Viral Infections in Common Variable Immunodeficiency (CVID) and CVID-like Disorders: A Literature Review

Al-Hakim,

Kacar,

Savic

2024

JCM

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Common Variable Immunodeficiency (CVID) is a heterogeneous primary immunodeficiency disorder characterised by impaired antibody production, leading to recurrent infections and an increased susceptibility to viral pathogens. This literature review aims to provide a comprehensive overview of CVID’s relationship with viral infections, encompassing disease pathogenesis, key presenting features, specific monogenic susceptibilities, the impact of COVID-19, and existing treatment options. The pathogenesis of CVID involves complex immunological dysregulation, including defects in B cell development, antibody class switching, and plasma cell differentiation. These abnormalities contribute to an impaired humoral immune response against viral agents, predisposing individuals with CVID to a broad range of viral infections. Genetic factors play a prominent role in CVID, and monogenic drivers of CVID-like disease are increasingly identified through advanced genomic studies. Some monogenic causes of the CVID-like phenotype appear to cause specific viral susceptibilities, and these are explored in the review. The emergence of the COVID-19 pandemic highlighted CVID patients’ heightened predisposition to severe outcomes with viral infections. This review explores the clinical manifestations, outcomes, and potential therapeutic approaches for COVID-19 in CVID patients. It assesses the efficacy of prophylactic measures for COVID-19, including vaccination and immunoglobulin replacement therapy, as well as trialled therapies.

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“…Based on these data together with pharmacodynamics and experience from phase 2, a dose of 100 mg once daily with a loading dose of 400 mg on day 1 was selected for the currently ongoing phase 3 trial in immunocompromised patients with acyclovir resistant mucocutaneous HSV infection (PRIOH‐1, NCT03073967) 11 . This dosing regimen was also successfully used in an international early access program with acyclovir resistant and foscarnet resistant or acyclovir resistant and foscarnet intolerant immunocompromised HSV patients 8,9,12 …”

mentioning

confidence: 99%

Mass Balance and Metabolite Profile after Single and Multiple Oral Doses of Pritelivir in Healthy Subjects

Bonsmann,

McCormick,

Pausch

et al. 2024

Clinical Pharm in Drug Dev

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Pritelivir is a helicase‐primase inhibitor active against HSV. Two human mass balance trials (a multiple‐dose trial and a single‐dose trial) were performed to characterize the absorption, distribution, metabolism, and excretion of 100 mg oral pritelivir combined with a single microdose of 14C‐pritelivir. Blood, urine, and feces samples were collected up to 26 days postdose. The plasma half‐life of pritelivir was 63‐67 hours. Overall, 92% and 66% of the administered dose was recovered in the multiple and single dose trials, respectively. The low recovery after the single dose (66%) was most likely related to the formulation used. The major metabolic pathway was amide hydrolysis leading to amino thiazole sulfonamide (ATS) and pyridinyl phenyl acetic acid (PPA). In plasma, pritelivir, ATS, PPA, and PPA‐acyl glucuronide accounted for 40.6%, 9.4%, 5.1%, and 0.2% of total radioactivity. More than 90% of drug‐related material was eliminated 624 hours postdose. The majority was excreted in urine (75% and 77%), followed by feces (16% and 23%). The main components in urine were PPA‐acyl glucuronide (and its isomers), ATS, and its N‐demethylated isomers. Only minor metabolites were observed in feces. In conclusion, the major metabolic pathways of pritelivir have been identified with the primary excretion route being renal.

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Salvage Treatment of Refractory HSV Oral Lesions with Pritelivir in Allogeneic Hematopoietic Cell Transplant Recipients

Cited by 11 publications

References 34 publications

Successful treatment of acyclovir‐resistant herpes simplex virus infection with amenamevir in a patient who received umbilical cord blood transplantation for T‐cell prolymphocytic leukemia

Successful treatment of acyclovir‐resistant herpes simplex virus infection with amenamevir in a patient who received umbilical cord blood transplantation for T‐cell prolymphocytic leukemia

The Scope and Impact of Viral Infections in Common Variable Immunodeficiency (CVID) and CVID-like Disorders: A Literature Review

Mass Balance and Metabolite Profile after Single and Multiple Oral Doses of Pritelivir in Healthy Subjects

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