A new-mechanism herpes pill clears the FDA for drug-refractory infections

The Food and Drug Administration approved pritelivir, to be sold as Hovilpri, on 9 October for the treatment of mucocutaneous herpes simplex virus (HSV) lesions in immunocompromised adults whose infection is refractory to aciclovir, valaciclovir, or famciclovir, with or without documented resistance [s1][s2]. It is the first HSV helicase-primase inhibitor to reach the US market, a mechanism distinct from the nucleoside analogues that have anchored herpes treatment for four decades [s1].

The distinction matters for one group in particular. In people whose immune systems are suppressed — after a stem-cell or organ transplant, during treatment for a blood cancer, or with advanced HIV — herpes outbreaks can become large, persistent and, over repeated courses of aciclovir, resistant. When that happens the fallback has been intravenous foscarnet or cidofovir, drugs given by infusion and limited by kidney toxicity. Pritelivir is a tablet.

What the label says

Treatment begins with a loading dose of 400 mg — four 100 mg tablets — on day one, followed by 100 mg once daily, with or without food, until the lesions have healed [s1]. There are no listed contraindications [s1].

The most consequential instruction concerns stomach-acid drugs. Pritelivir absorption falls when gastric pH rises, so the label tells patients to avoid the proton-pump inhibitors esomeprazole and rabeprazole outright, to cap omeprazole or lansoprazole at 20 mg a day and pantoprazole at 40 mg, to separate any H2-blocker from pritelivir by set intervals, and to space antacids two hours apart [s1]. Reduced exposure, the label warns, risks both lost efficacy and the emergence of resistance [s1].

The evidence

Approval rests mainly on Part C of the PRIOH-1 trial (NCT03073967), a randomised, open-label, comparator-controlled superiority study [s1]. A total of 101 immunocompromised adults with refractory mucocutaneous HSV were assigned one-to-one to pritelivir or to Investigator's Choice — intravenous foscarnet, intravenous or topical cidofovir, or 5% topical imiquimod — for up to 28 days, extended to 42 if lesions were improving [s1].

The enrolled population reflected the intended use. Mean age was 53 (range 19 to 84), and the underlying conditions included haematological malignancy or disorder in 47%, haematopoietic stem-cell transplantation in 40%, HIV infection in 38%, autoimmune or inflammatory disease in 29%, and solid-organ transplantation in 4% [s1]. Twenty-nine per cent had laboratory-confirmed aciclovir resistance; the remainder were clinically refractory [s1]. Foscarnet was the comparator in 70% of the control arm [s1].

The primary endpoint was the proportion of participants with all lesions healed by complete epithelialisation within 28 days. Thirty-two of 51 on pritelivir reached it (63%) against 17 of 50 on Investigator's Choice (34%), an adjusted difference of 28.4 percentage points (95% CI 9.6 to 47.3; p=0.0047) [s1]. By day 42, the response rates were 82% and 42%, an adjusted difference of 40 points (95% CI 22.7 to 57.7); a third of the pritelivir arm used the extended window [s1].

A separate single-arm portion, Parts D and F, treated 35 adults with aciclovir- and foscarnet-refractory disease or foscarnet intolerance; 40% healed by day 28 and 66% by day 42 [s1].

Safety, as far as it goes

Across the programme, 206 adults received pritelivir [s1]. In Part C, adverse reactions were reported in 22% of pritelivir recipients against 54% of the comparator arm, and discontinuations for adverse reactions in 2% versus 20% — differences that partly reflect the toxicity of infused comparators [s1]. The only adverse reaction above 5% on pritelivir was headache, at 6% [s1]. Liver-enzyme elevations of at least 2.5 times the upper limit of normal occurred in 8% (ALT) and 6% (AST) of the pritelivir group, and one participant stopped treatment for raised enzymes [s1].

What is and is not established

The trial tested mucocutaneous disease only. Participants with ocular, central-nervous-system or disseminated HSV were excluded, so the label says nothing about those presentations [s1]. The comparison was against a mix of existing agents rather than a single standard, the numbers are small, and there are no human pregnancy data [s1]. Because HSV establishes lifelong latent infection, the label is explicit that treatment is not curative [s1]. What the evidence supports is narrower and still useful: in refractory disease, an oral drug healed more lesions than infused alternatives, in exactly the patients for whom the infused options are hardest to give.

Red flags: anyone immunosuppressed with a herpes lesion that is spreading, not healing, or affecting the eye should seek urgent medical review rather than wait. This article describes regulatory and research news and is not medical advice. Decisions about antiviral treatment are for patients and their treating clinicians.