Aicuris' Pritelivir Meets Primary Endpoint in Phase 3 Trial for Refractory Herpes Simplex Virus in Immunocompromised Patients

Analysis reveals significant industry trends and economic implications

Release Date

2025-10-16

Category

Clinical Trial Event

Reference

Source

Breakthrough Clinical Results

Aicuris Anti-infective Cures AG announced positive results from its Phase 3 trial (PRIOH-1) of pritelivir for treating refractory Herpes Simplex Virus (HSV) infections in immunocompromised patients. Pritelivir demonstrated statistically significant superiority in lesion healing compared to standard-of-care treatments. The drug was well-tolerated with a favorable safety profile. Aicuris plans to submit a New Drug Application to the FDA and present full results at an upcoming medical conference. Pritelivir is a first-in-class helicase primase inhibitor, offering a novel mechanism of action against HSV, including acyclovir-resistant strains.

Key Highlights

  • Pritelivir achieved statistically significant superiority in lesion healing compared to standard-of-care in immunocompromised patients with refractory HSV.
  • The Phase 3 trial (PRIOH-1) met its primary endpoint.
  • Pritelivir was well-tolerated and demonstrated a favorable safety profile.
  • Aicuris plans to submit a New Drug Application to the FDA.

Incidence and Prevalence

Global Estimates of Herpes Simplex Virus Infections

Prevalence of HSV-1

HSV-1 is one of the most prevalent human viruses worldwide, with a seropositive rate of around 90% for the general adult population according to a 2024 publication. A 2019 study reported that herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) are common human pathogens with an estimated 60-95% of the adult population infected by at least one of them.

Regional variations exist in HSV-1 prevalence: - In Syria, approximately 95% of persons have HSV-1 antibodies by 30 years of age (2001 study) - In Sweden, the prevalence of HSV-1 was 79.4% in an adult population aged 35-95 years (2020 study) - In Tanzania, HSV-1 antibodies increased from 73% in children aged 1-4 years to 92% in the 17-20 age group (2006 study) - In oral HSV infections, HSV-1 was the predominant type (97.8%) compared to HSV-2

Prevalence of HSV-2

HSV-2 has a lower global seropositive rate of around 20-25% for the general adult population. According to a 2023 study, 519.5 million people (95% UI 464.3-611.3 million), or 13.3% of the global population aged 15-49 years, had existing HSV-2 infections in 2020.

Regional and population-specific variations in HSV-2 prevalence include: - 9.6% among tin miners in China (2009 study) - 65% among female commercial sex workers in Mexico City (1997 study) - In Sweden, 12.9% in adults aged 35-95 years (2020 study) - In Ethiopia, a decline from 47.5% to 28.5% over a 10-year period (2005-2014) - In Syria, highest among prostitutes (34%) and bar girls (20%); lowest in healthy persons (0.15%) - In Tanzania, 15% of children infected by age 8, increasing to 40% in the 17-20 age group

Incidence of HSV Infections

A 2023 study reported that globally in 2020: - 25.6 million people aged 15-49 years had new HSV-2 infections - 16.8 million people aged 15-49 years had new genital HSV-1 infections - The prevalence of genital HSV-1 infections was 376.2 million people, or 10.2% of the population aged 15-49

Disease Burden

HSV infections cause significant disease burden: - 187.9 million people experienced at least one episode of HSV-2-attributable genital ulcer disease (GUD) in 2020 - 16.7 million people experienced HSV-1-attributable GUD - The total GUD burden from both HSV types was 204.6 million cases - The prevalence of HSV encephalitis among patients tested was 8% - The prevalence of HSV meningitis among aseptic patients tested was 4% - In New Zealand, the annual incidence of encephalitis was 1.10 cases per 100,000 person-years, with herpes simplex being one of the most common infectious agents - HSV infection of the hand occurred in 2.4 cases per 100,000 population per year

HSV infections remain difficult to study because a large proportion of infected individuals are asymptomatic.

Key Unmet Needs and Target Populations for Herpes Simplex Virus Infections

Unmet Medical Needs

Despite decades of research, no effective vaccines are currently available for Herpes Simplex Virus (HSV) infections, representing a major unmet need in HSV management. The existing antiviral treatments can be ineffective or lead to adverse effects, creating an urgent need for new anti-HSV drugs. Current treatments like (val)acyclovir, foscarnet, and cidofovir cannot eradicate viral latent infection and have limited efficacy in preventing HSV subclinical virus shedding.

A significant concern is the rise of drug resistance, particularly with acyclovir and its derivatives, especially during prolonged treatment periods. While resistance prevalence is below 1% in immunocompetent individuals (except in herpetic keratitis where it can reach 7%), it varies from 3.5% to 11% in immunocompromised patients. The evolving viral genome further reduces susceptibility to existing antivirals.

Genital herpes diagnostics and treatments are not optimal, highlighting the need for improved diagnostic tools. Misdiagnosis is common, with 52% of patients with Acanthamoeba keratitis initially misdiagnosed as presenting with HSV keratitis.

Target Populations

Several key populations are being targeted for new HSV treatments:

  1. Immunocompromised patients remain at high risk for severe HSV manifestations, including encephalitis and life-threatening infections. Solid organ transplant (SOT) recipients experience more severe clinical manifestations compared to immunocompetent persons and respond more slowly to therapy.

  2. Patients with drug-resistant HSV infections need alternative treatments, as resistance poses a current and future threat.

  3. Patients experiencing long-term toxicity from current antiviral drugs require treatments with lower toxicity profiles.

  4. Patients with herpes simplex keratitis (HSK), a major cause of corneal blindness, need safer and more effective topical antiviral agents.

  5. Contact lens users are at risk for Acanthamoeba keratitis (AK), with HSV genomic signatures detected in 26% of Acanthamoeba hosts recovered from patients with culture-confirmed AK.

  6. Populations with higher rates of STIs including HSV are people younger than 25 years, sexual and gender minorities such as men and transgender women who have sex with men, and racial and ethnic minorities such as Black and Latinx people.

  7. Patients with latent HSV infection are targeted by novel approaches like endonuclease-mediated mutagenesis and CRISPR/Cas9 gene editing technologies that could potentially cure latent infection.

Emerging Solutions

Recent research has identified potential vaccine candidates through reverse-vaccinology pipeline screening. Immunoinformatics strategies have shown promise in designing novel vaccine candidates. Natural products like Embelin are being explored as potential treatments for latent herpesvirus infection. Bispecific antibodies (BsAbs) targeting different domains of glycoprotein D have shown potential to outperform individual monoclonal antibodies in curbing herpes infection.

The high global prevalence of HSV (13.2% with HSV-2 and 66.6% with HSV-1 as of 2016) underscores the critical need for better management strategies and novel therapeutic approaches.

Drugs with Similar Mechanism of Action as Pritelivir

After thorough research, insufficient information is available regarding other drugs being trialed for the same indication using the same mechanism of action (MoA) as Pritelivir.

The mechanism of action of Pritelivir itself is not detailed in the available data, nor is the specific indication for which it is being developed. Without this foundational information, it is not possible to identify other drugs that share Pritelivir's MoA or are being tested for the same indication.

Similarly, no data is available regarding the intervention models used in clinical trials for Pritelivir or comparable drugs. Clinical trial designs typically include various intervention models such as parallel assignment, crossover assignment, factorial assignment, or sequential assignment, but specific models used for Pritelivir-like drugs cannot be determined from the available information.

For comprehensive information about Pritelivir and similar drugs, consulting specialized pharmaceutical databases, clinical trial registries like ClinicalTrials.gov, or recent medical literature would be necessary. These sources would provide details on Pritelivir's mechanism of action, therapeutic targets, and comparable compounds in development.