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 7 publications

(2 citation statements)

References 34 publications

(28 reference statements)

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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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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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“…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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Evaluation of the Clinical Drug‐Drug Interaction Potential of Pritelivir on Transporters and CYP450 Enzymes Using a Cocktail Approach

de Vries,

Bonsmann,

Pausch

et al. 2024

Clinical Pharm in Drug Dev

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Pritelivir is a novel viral helicase‐primase inhibitor active against herpes simplex virus. In vitro drug‐drug interaction studies indicated that pritelivir has the potential for clinically relevant interactions on the cytochrome P450 (CYP) enzymes 2C8, 2C9, 3A4, and 2B6, and intestinal uptake transporter organic anion transporting polypeptide (OATP) 2B1 and efflux transporter breast cancer resistance protein (BCRP). This was evaluated in 2 clinical trials. In 1 trial the substrates flurbiprofen (CYP2C9), bupropion (CYP2B6), and midazolam (CYP3A4) were administered simultaneously as part of the Geneva cocktail, while the substrate celiprolol (OAPT2B1) was administered separately. In another trial, the substrates repaglinide (CYP2C8) and rosuvastatin (BCRP) were administered separately. Exposure parameters of the substrates and their metabolites (flurbiprofen and bupropion only) were compared after administration with or without pritelivir under therapeutic concentrations. The results of these trials indicated that pritelivir has no clinically relevant effect on the exposure of substrates for the intestinal uptake transporter OATP2B1 and the CYP enzymes 3A4, 2B6, 2C9, and 2C8, and has a weak inhibitory effect on the intestinal efflux transporter BCRP. In summary, the results suggest that pritelivir has a low drug‐drug interaction potential.

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

Cited by 7 publications

References 34 publications

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

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

Evaluation of the Clinical Drug‐Drug Interaction Potential of Pritelivir on Transporters and CYP450 Enzymes Using a Cocktail Approach

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