An oral antiviral showed encouraging efficacy and a favorable safety profile compared with intravenous foscarnet for treating acyclovir-refractory herpes simplex virus infection in immunocompromised adults in a Phase 2 trial, according to a randomized study published in Open Forum Infectious Diseases.
The multicenter, open-label study evaluated pritelivir, a helicase-primase inhibitor with a mechanism of action distinct from standard herpes simplex virus treatments. The authors noted that immunocompromised patients can experience severe, prolonged HSV infections and have limited treatment options when infections do not respond to acyclovir or related antivirals. Foscarnet is the only FDA-approved alternative for acyclovir-refractory HSV infection, but its use can be limited by adverse effects, including nephrotoxicity and electrolyte abnormalities, as well as the need for intravenous administration and close monitoring.
The trial included 28 immunocompromised adults with acyclovir-refractory HSV infection at 14 U.S. centers. In the randomized portion of the study, 22 participants received either oral pritelivir or intravenous foscarnet for up to 28 days. An additional eight participants with HSV infection that was refractory to or intolerant of foscarnet received pritelivir; two of those participants transferred from the randomized portion of the study.
The primary outcome was time to complete lesion healing, assessed through independent photographic review. According to the study, the median time to healing was 26 days among participants receiving pritelivir, while the median could not be estimated in the foscarnet group because fewer than half of participants were assessed as healed. The difference in time to healing was not statistically significant.
Investigator assessments found that 93% of participants receiving pritelivir achieved lesion healing compared with 57% of those receiving foscarnet, although that difference also did not reach statistical significance. HSV DNA was detected less frequently after baseline among participants receiving pritelivir than among those receiving foscarnet, but the difference was not statistically significant, according to the study.
“Despite the lack of statistical significance, the treatment differences demonstrated a beneficial effect numerically, with a higher lesion healing rate on pritelivir compared with foscarnet,” the authors wrote.
The study also found fewer treatment-emergent adverse events among participants receiving pritelivir. All participants receiving foscarnet experienced at least one treatment-emergent adverse event compared with 60% of participants receiving pritelivir. Serious and severe treatment-emergent adverse events also occurred more frequently in the foscarnet group, according to the study authors. No treatment-emergent adverse events led to discontinuation of pritelivir in the randomized portion of the trial, while three participants discontinued foscarnet because of adverse events.
Three deaths occurred in the randomized portion of the study — two among participants receiving foscarnet and one among those receiving pritelivir. Investigators determined that none were related to the study medications, according to the authors.
Among the eight participants who received pritelivir because their HSV infection was refractory or resistant to foscarnet or because they were intolerant of foscarnet, five achieved lesion healing. One serious adverse event of rash was considered related to pritelivir and resulted in hospitalization. No deaths occurred in this portion of the study.
The authors cautioned that the findings should be interpreted in light of the study’s small sample size and the heterogeneity of participants’ underlying immunosuppressive conditions. The study was also not designed or powered to detect statistical differences between treatments. In addition, because more participants receiving pritelivir achieved healing, more of those participants contributed to the analysis of lesion recurrence, potentially introducing bias.
“In summary, pritelivir demonstrated encouraging efficacy and a favorable safety profile in immunocompromised patients with ACV R ± R HSV infection,” the authors wrote. “Further evaluation is ongoing in a global Phase 3 trial, which aims to confirm these findings in a larger and more diverse patient cohort.”
The study was supported by AiCuris Anti-Infective Cures AG, and several authors reported relationships with AiCuris and other pharmaceutical companies. Three authors were employees of AiCuris, and two were former employees. Other authors reported no potential conflicts of interest.