Helicase-primase inhibitor pritelivir for HSV-2 infection

Anna Wald, Lawrence Corey, Burkhard Timmler, Amalia Magaret, Terri Warren, Stephen Tyring, Christine Johnston, John Kriesel, Kenneth Fife, Lawrence Galitz, Susanne Stoelben, Meei Li Huang, Stacy Selke, Hans Peter Stobernack, Helga Ruebsamen-Schaeff, Alexander Birkmann

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Background: Pritelivir, an inhibitor of the viral helicase-primase complex, exhibits antiviral activity in vitro and in animal models of herpes simplex virus (HSV) infection. We tested the efficacy and safety of pritelivir in otherwise healthy persons with genital HSV-2 infection. Methods: We randomly assigned 156 HSV-2-positive persons with a history of genital herpes to receive one of four doses of oral pritelivir (5, 25, or 75 mg daily, or 400 mg weekly) or placebo for 28 days. Participants obtained daily swabs from the genital area for HSV-2 testing, which was performed with a polymerase-chain-reaction assay. Participants also maintained a diary of genital signs and symptoms. The primary end point was the rate of genital HSV shedding. Results: HSV shedding among placebo recipients was detected on 16.6% of days; shedding among pritelivir recipients was detected on 18.2% of days among those receiving 5 mg daily, 9.3% of days among those receiving 25 mg daily, 2.1% of days among those receiving 75 mg daily, and 5.3% of days among those receiving 400 mg weekly. The relative risk of viral shedding with pritelivir, as compared with placebo, was 1.11 (95% confidence interval [CI], 0.65 to 1.87) with the 5-mg daily dose, 0.57 (95% CI, 0.31 to 1.03) with the 25-mg daily dose, 0.13 (95% CI, 0.04 to 0.38) with the 75-mg daily dose, and 0.32 (95% CI, 0.17 to 0.59) with the 400-mg weekly dose. The percentage of days with genital lesions was also significantly reduced, from 9.0% in the placebo group to 1.2% in both the group receiving 75 mg of pritelivir daily (relative risk, 0.13; 95% CI, 0.02 to 0.70) and the group receiving 400 mg weekly (relative risk, 0.13; 95% CI, 0.03 to 0.52). The rate of adverse events was similar in all groups. Conclusions: Pritelivir reduced the rates of genital HSV shedding and days with lesions in a dosedependent manner in otherwise healthy men and women with genital herpes.

Original languageEnglish (US)
Pages (from-to)201-210
Number of pages10
JournalNew England Journal of Medicine
Volume370
Issue number3
DOIs
StatePublished - Jan 1 2014

Fingerprint

DNA Primase
Human Herpesvirus 2
Herpes Genitalis
Virus Diseases
Virus Shedding
Simplexvirus
Confidence Intervals
Placebos
BAY 57-1293
Signs and Symptoms
Antiviral Agents
Animal Models
Safety
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Wald, A., Corey, L., Timmler, B., Magaret, A., Warren, T., Tyring, S., ... Birkmann, A. (2014). Helicase-primase inhibitor pritelivir for HSV-2 infection. New England Journal of Medicine, 370(3), 201-210. https://doi.org/10.1056/NEJMoa1301150

Helicase-primase inhibitor pritelivir for HSV-2 infection. / Wald, Anna; Corey, Lawrence; Timmler, Burkhard; Magaret, Amalia; Warren, Terri; Tyring, Stephen; Johnston, Christine; Kriesel, John; Fife, Kenneth; Galitz, Lawrence; Stoelben, Susanne; Huang, Meei Li; Selke, Stacy; Stobernack, Hans Peter; Ruebsamen-Schaeff, Helga; Birkmann, Alexander.

In: New England Journal of Medicine, Vol. 370, No. 3, 01.01.2014, p. 201-210.

Research output: Contribution to journalArticle

Wald, A, Corey, L, Timmler, B, Magaret, A, Warren, T, Tyring, S, Johnston, C, Kriesel, J, Fife, K, Galitz, L, Stoelben, S, Huang, ML, Selke, S, Stobernack, HP, Ruebsamen-Schaeff, H & Birkmann, A 2014, 'Helicase-primase inhibitor pritelivir for HSV-2 infection', New England Journal of Medicine, vol. 370, no. 3, pp. 201-210. https://doi.org/10.1056/NEJMoa1301150
Wald A, Corey L, Timmler B, Magaret A, Warren T, Tyring S et al. Helicase-primase inhibitor pritelivir for HSV-2 infection. New England Journal of Medicine. 2014 Jan 1;370(3):201-210. https://doi.org/10.1056/NEJMoa1301150
Wald, Anna ; Corey, Lawrence ; Timmler, Burkhard ; Magaret, Amalia ; Warren, Terri ; Tyring, Stephen ; Johnston, Christine ; Kriesel, John ; Fife, Kenneth ; Galitz, Lawrence ; Stoelben, Susanne ; Huang, Meei Li ; Selke, Stacy ; Stobernack, Hans Peter ; Ruebsamen-Schaeff, Helga ; Birkmann, Alexander. / Helicase-primase inhibitor pritelivir for HSV-2 infection. In: New England Journal of Medicine. 2014 ; Vol. 370, No. 3. pp. 201-210.
@article{a03e9123a9b74290acaf7b1e8528bbfe,
title = "Helicase-primase inhibitor pritelivir for HSV-2 infection",
abstract = "Background: Pritelivir, an inhibitor of the viral helicase-primase complex, exhibits antiviral activity in vitro and in animal models of herpes simplex virus (HSV) infection. We tested the efficacy and safety of pritelivir in otherwise healthy persons with genital HSV-2 infection. Methods: We randomly assigned 156 HSV-2-positive persons with a history of genital herpes to receive one of four doses of oral pritelivir (5, 25, or 75 mg daily, or 400 mg weekly) or placebo for 28 days. Participants obtained daily swabs from the genital area for HSV-2 testing, which was performed with a polymerase-chain-reaction assay. Participants also maintained a diary of genital signs and symptoms. The primary end point was the rate of genital HSV shedding. Results: HSV shedding among placebo recipients was detected on 16.6{\%} of days; shedding among pritelivir recipients was detected on 18.2{\%} of days among those receiving 5 mg daily, 9.3{\%} of days among those receiving 25 mg daily, 2.1{\%} of days among those receiving 75 mg daily, and 5.3{\%} of days among those receiving 400 mg weekly. The relative risk of viral shedding with pritelivir, as compared with placebo, was 1.11 (95{\%} confidence interval [CI], 0.65 to 1.87) with the 5-mg daily dose, 0.57 (95{\%} CI, 0.31 to 1.03) with the 25-mg daily dose, 0.13 (95{\%} CI, 0.04 to 0.38) with the 75-mg daily dose, and 0.32 (95{\%} CI, 0.17 to 0.59) with the 400-mg weekly dose. The percentage of days with genital lesions was also significantly reduced, from 9.0{\%} in the placebo group to 1.2{\%} in both the group receiving 75 mg of pritelivir daily (relative risk, 0.13; 95{\%} CI, 0.02 to 0.70) and the group receiving 400 mg weekly (relative risk, 0.13; 95{\%} CI, 0.03 to 0.52). The rate of adverse events was similar in all groups. Conclusions: Pritelivir reduced the rates of genital HSV shedding and days with lesions in a dosedependent manner in otherwise healthy men and women with genital herpes.",
author = "Anna Wald and Lawrence Corey and Burkhard Timmler and Amalia Magaret and Terri Warren and Stephen Tyring and Christine Johnston and John Kriesel and Kenneth Fife and Lawrence Galitz and Susanne Stoelben and Huang, {Meei Li} and Stacy Selke and Stobernack, {Hans Peter} and Helga Ruebsamen-Schaeff and Alexander Birkmann",
year = "2014",
month = "1",
day = "1",
doi = "10.1056/NEJMoa1301150",
language = "English (US)",
volume = "370",
pages = "201--210",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "3",

}

TY - JOUR

T1 - Helicase-primase inhibitor pritelivir for HSV-2 infection

AU - Wald, Anna

AU - Corey, Lawrence

AU - Timmler, Burkhard

AU - Magaret, Amalia

AU - Warren, Terri

AU - Tyring, Stephen

AU - Johnston, Christine

AU - Kriesel, John

AU - Fife, Kenneth

AU - Galitz, Lawrence

AU - Stoelben, Susanne

AU - Huang, Meei Li

AU - Selke, Stacy

AU - Stobernack, Hans Peter

AU - Ruebsamen-Schaeff, Helga

AU - Birkmann, Alexander

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background: Pritelivir, an inhibitor of the viral helicase-primase complex, exhibits antiviral activity in vitro and in animal models of herpes simplex virus (HSV) infection. We tested the efficacy and safety of pritelivir in otherwise healthy persons with genital HSV-2 infection. Methods: We randomly assigned 156 HSV-2-positive persons with a history of genital herpes to receive one of four doses of oral pritelivir (5, 25, or 75 mg daily, or 400 mg weekly) or placebo for 28 days. Participants obtained daily swabs from the genital area for HSV-2 testing, which was performed with a polymerase-chain-reaction assay. Participants also maintained a diary of genital signs and symptoms. The primary end point was the rate of genital HSV shedding. Results: HSV shedding among placebo recipients was detected on 16.6% of days; shedding among pritelivir recipients was detected on 18.2% of days among those receiving 5 mg daily, 9.3% of days among those receiving 25 mg daily, 2.1% of days among those receiving 75 mg daily, and 5.3% of days among those receiving 400 mg weekly. The relative risk of viral shedding with pritelivir, as compared with placebo, was 1.11 (95% confidence interval [CI], 0.65 to 1.87) with the 5-mg daily dose, 0.57 (95% CI, 0.31 to 1.03) with the 25-mg daily dose, 0.13 (95% CI, 0.04 to 0.38) with the 75-mg daily dose, and 0.32 (95% CI, 0.17 to 0.59) with the 400-mg weekly dose. The percentage of days with genital lesions was also significantly reduced, from 9.0% in the placebo group to 1.2% in both the group receiving 75 mg of pritelivir daily (relative risk, 0.13; 95% CI, 0.02 to 0.70) and the group receiving 400 mg weekly (relative risk, 0.13; 95% CI, 0.03 to 0.52). The rate of adverse events was similar in all groups. Conclusions: Pritelivir reduced the rates of genital HSV shedding and days with lesions in a dosedependent manner in otherwise healthy men and women with genital herpes.

AB - Background: Pritelivir, an inhibitor of the viral helicase-primase complex, exhibits antiviral activity in vitro and in animal models of herpes simplex virus (HSV) infection. We tested the efficacy and safety of pritelivir in otherwise healthy persons with genital HSV-2 infection. Methods: We randomly assigned 156 HSV-2-positive persons with a history of genital herpes to receive one of four doses of oral pritelivir (5, 25, or 75 mg daily, or 400 mg weekly) or placebo for 28 days. Participants obtained daily swabs from the genital area for HSV-2 testing, which was performed with a polymerase-chain-reaction assay. Participants also maintained a diary of genital signs and symptoms. The primary end point was the rate of genital HSV shedding. Results: HSV shedding among placebo recipients was detected on 16.6% of days; shedding among pritelivir recipients was detected on 18.2% of days among those receiving 5 mg daily, 9.3% of days among those receiving 25 mg daily, 2.1% of days among those receiving 75 mg daily, and 5.3% of days among those receiving 400 mg weekly. The relative risk of viral shedding with pritelivir, as compared with placebo, was 1.11 (95% confidence interval [CI], 0.65 to 1.87) with the 5-mg daily dose, 0.57 (95% CI, 0.31 to 1.03) with the 25-mg daily dose, 0.13 (95% CI, 0.04 to 0.38) with the 75-mg daily dose, and 0.32 (95% CI, 0.17 to 0.59) with the 400-mg weekly dose. The percentage of days with genital lesions was also significantly reduced, from 9.0% in the placebo group to 1.2% in both the group receiving 75 mg of pritelivir daily (relative risk, 0.13; 95% CI, 0.02 to 0.70) and the group receiving 400 mg weekly (relative risk, 0.13; 95% CI, 0.03 to 0.52). The rate of adverse events was similar in all groups. Conclusions: Pritelivir reduced the rates of genital HSV shedding and days with lesions in a dosedependent manner in otherwise healthy men and women with genital herpes.

UR - http://www.scopus.com/inward/record.url?scp=84892608050&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84892608050&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1301150

DO - 10.1056/NEJMoa1301150

M3 - Article

C2 - 24428466

AN - SCOPUS:84892608050

VL - 370

SP - 201

EP - 210

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 3

ER -