Aicuris Anti-infective Cures AG announced that its lead candidate pritelivir has achieved its primary endpoint in a registrational Phase 3 trial, demonstrating statistically significant superiority in treating refractory herpes simplex virus (HSV) infections in immunocompromised patients. The trial results mark a potential breakthrough in HSV treatment, representing the first therapeutic innovation for this patient population in over two decades.
Phase 3 Trial Results Demonstrate Superior Efficacy
The PRIOH-1 trial (NCT03073967) met its primary endpoint, showing pritelivir's clinically meaningful and highly statistically significant superiority (p=0.0047) in lesion healing up to 28 days of treatment compared with standard-of-care treatments. Statistical superiority further increased in patients receiving up to 42 days of treatment (p<0.0001).
The open-label, comparative trial was conducted across 15 countries and enrolled 158 immunocompromised participants. In the randomized portion, 102 patients with refractory and/or treatment-resistant HSV were treated with either pritelivir or investigator's choice of standard-of-care options including foscarnet, cidofovir, compounded topical cidofovir, or imiquimod.
All pritelivir-treated patients received a loading dose of 400 mg on the first day of treatment followed by 100 mg daily until all lesions were healed. The trial also included two additional non-randomized cohorts: 35 patients who were resistant to both acyclovir and foscarnet or intolerant to foscarnet, and 21 acyclovir-sensitive patients.
Novel Mechanism Addresses Treatment-Resistant Infections
Pritelivir is a first-in-class small-molecule antiviral that targets the helicase-primase complex of HSV, representing a novel mechanism of action distinct from current HSV therapies. Unlike traditional antivirals, pritelivir blocks viral DNA synthesis by inhibiting the helicase-primase complex rather than relying on activation by viral enzymes.
"As a clinician who treats immunocompromised patients and understands how HSV infections disrupt their lives, I view this Phase 3 as a significant step forward," said Genovefa Papanicolaou, MD, Clinical Director of Infectious Disease Service at Memorial Sloan Kettering Cancer Center. "There has been no HSV treatment innovation for this patient group for decades and pritelivir has the potential to be life-changing in particular for resistant patients where an orally available and safe option could significantly improve quality of life."
This distinct mechanism allows pritelivir to overcome HSV infections that are resistant or refractory to current treatments such as acyclovir, valacyclovir, famciclovir, and foscarnet. The drug's activity against resistant viral strains addresses a critical gap in treatment options for immunocompromised patients who frequently experience treatment failures with existing therapies.
Addressing Critical Unmet Medical Need
HSV infections pose particular challenges for immunocompromised patients, who are prone to more severe, prolonged, and refractory infections that do not respond to standard treatments. These infection outbreaks can cause painful lesions, drastically reducing quality of life and increasing the risk of hospitalization and disseminated infection.
Current standard-of-care treatments often require intravenous infusions and are poorly tolerated, with common side effects including kidney toxicity and electrolyte imbalances with risk of seizures requiring in-patient hospital management. Pritelivir's oral formulation and favorable safety profile could address these limitations.
"An HSV infection can be a serious health burden for immunocompromised patients, particularly when the virus no longer responds to standard treatments," said Cynthia Wat, MD, CMO of Aicuris. "Despite this high medical need, no new HSV therapies have been approved in over two decades, leaving clinicians with limited therapeutic choices, which are often not well tolerated, in a clinically vulnerable patient population."
Regulatory Path Forward
The positive Phase 3 results build on pritelivir's previous clinical success and its FDA Breakthrough Therapy designation received in 2020. Earlier Phase 1 and Phase 2 trials in immunocompetent and immunocompromised individuals showed a favorable safety profile and promising clinical efficacy compared to standard-of-care treatments like valacyclovir and foscarnet.
"After working in the infectious disease space for over 20 years, I am excited to have the opportunity to state - we have achieved our goal of demonstrating pritelivir's statistically superior treatment benefit in a registrational study," said Larry Edwards, CEO of Aicuris. "We plan to rapidly advance our New Drug Application submission to the FDA, and we look forward to presenting a comprehensive analysis of these positive results at a medical conference next year."
The company expects to present full results at an upcoming medical conference and plans to use the data as the basis for regulatory filings with the FDA and globally, with marketing authorization filings anticipated in 2026.
Global Disease Burden
According to the World Health Organization, HSV infections represent a significant global health burden. An estimated 3.8 billion people under age 50, or 64% of the global population, were infected with HSV-1 in 2020, while 520 million people aged 15 to 49 were living with genital herpes caused by HSV-2. The disease burden is particularly high in immunocompromised patients, who may experience more severe, frequent, and treatment-refractory manifestations.
