Herpes simplex viruses (HSV) are common infections caused mainly by HSV-1 (usually oral) and HSV-2 (usually genital), although either type can affect the mouth or genitals. The virus is highly prevalent and causes lifelong infection associated with a significant global burden of disease. It spreads through direct contact with infected skin or mucosa, often without symptoms, and establishes a latent infection in sensory nerves with periodic reactivation and viral shedding. Current antiviral therapies are limited by incomplete suppression of viral replication and have no effect on the latent viral reservoir, resulting in persistent viral shedding, recurrences, and drug resistance.
However, Innovative Molecules’ adibelivir (IM-250), a novel helicase-primase inhibitor, has shown nanomolar potency against clinical and acyclovir-resistant HSV strains, and superior efficacy in animal models affecting the latent viral reservoir.
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According to data from a Phase I/Ib study presented at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Global conference, HSV strains were isolated in the clinic and evaluated for susceptibility to adibelivir using a plaque reduction assay. Male and female participants received single oral doses of adibelivir (50mg, 100mg, or 200mg) or multiple oral doses (25mg), and plasma samples were collected for non-compartmental pharmacokinetic analysis using validated high-performance mass-spectrometry. Safety endpoints included treatment-emergent adverse events (TEAEs), laboratory assessments, vital signs, and electrocardiograms.
Adibelivir demonstrated potent antiviral activity against HSV clinical isolates including acyclovir-resistant strains. The drug was well tolerated in doses up to 200mg in Phase I clinical trials. No dose-limiting toxicities occurred. The half-life of adibelivir in human volunteers was approximately five days, and it was quickly absorbed, reaching a peak concentration of 1.2µg/ml, 2.3µg/ml, and 3.7µg/ml after single oral doses of 50mg, 100mg, and 200mg, respectively, or 5.6µg/ml after multiple daily doses of 25mg. Furthermore, testing in animal models showed that adibelivir affected the latent viral reservoir, suggesting that it has potential as a long-term curative therapy for HSV.
In conclusion, treatment with adibelivir proved safe and efficacious in Phase I clinical trials. The favourable pharmacokinetic profile supports further development in HSV-infected patients as clinical isolates are highly susceptible to adibelivir. Early clinical data positions this drug as a first-in-class, disease-modifying HSV therapy with the potential to reshape the treatment of recurrent and drug-resistant oral and genital herpes. HSV is a large, chronic market with high global prevalence and persistent unmet need around recurrence burden, adherence to frequent dosing, and lack of options for resistant disease. Hence, the commercial opportunity for this drug candidate is significant.
