1. In this randomized controlled trial, pritelivir was effective in reducing the number of HSV-2 positive swabs, total days with herpetic lesions, and the number of days of reported pain when compared to valacyclovir.
2. Though this trial was put on clinical hold by the FDA due to dermatological side-effects in non-human primates, there was no increase in dermatological and hematological side effects of pritelivir compared to valacyclovir during the study.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Current treatment for herpes simplex virus 2 (HSV-2) consists of nucleoside analogs that inhibit viral replication. While these agents reduce clinical recurrences, they are not entirely effective. Pritelivir blocks a helicase-primase complex involved in replication and may control viral replication more effectively than current therapies. In this randomized controlled trial, pritelivir was found to reduce the number of HSV-2 positive swabs when compared to valacyclovir in patients with multiple recurrences. Sheddings were reduced during subclinical periods but not when lesions were detected. A reduced frequency of sheddings did not reach significance with pritelivir, though an increase in shedding episodes lasting less than 24 hours was detected. The total number of days with lesions was reduced with pritelivir compared to valacyclovir, as was reported pain. The rate of adverse effects was similar between pritelivir and valacyclovir. Importantly, this trial was put on clinical hold before completion due to dermatological and hematological adverse events in non-human primates.
The results of this trial were very promising and non-significant findings may have been a product of low statistical power, as the study was not completed as designed. Though sponsored by the drug company Aicuris, this study was well designed and statistical analyses were done by a University of Washington group not associated with the company. Still, further investigation is needed to determine how effective pritelivir might be for all HSV-2 patient populations and whether the adverse events in primates are a concern for patients.
Relevant Reading: Helicase-primase inhibitor pritelivir for HSV-2 infection
In-Depth [randomized controlled trial]: Conducted at four clinical research centers, this double-blind, crossover, randomized controlled trial enrolled 91 patients with recurrent HSV-2 lesions and randomized them to receive either valacyclovir or pritelivir. Patients were split into two groups and started taking valacyclovir or pritelivir for 28 days, followed by a 28-day washout period before initiating the other drug for 28 days. Because of a clinical hold by the FDA due to concerns of dermatological and hematological adverse events in non-human primates, only 56 patients completed both arms of the study while 76 completed one treatment regimen. The number of HSV-2 positive swabs was decreased when taking pritelivir with a relative risk of 0.42 (CI95 0.21-0.82). The HSV-2 copy number did not differ by group in positive swabs. The frequency of subclinical shedding was lower with pritelivir (RR 0.40; CI95 0.20-0.81) but not when lesions were observed. The frequency of shedding was not found to be different (RR 0.80; CI95 0.52-1.22; p = 0.29) but the number of recurrences lasting less than 24 hours was increased with pritelivir (87% vs 69%; p = 0.005). The recurrence of lesions was less frequent with pritelivir (RR 0.40; CI95 0.17-0.96) and the number of days with reported pain was also reduced (RR 0.53; CI95 0.30-0.93). There were no differences in the rates of adverse effects between pritelivir and valacyclovir.
©2016 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.