Groundbreaking Trial Tests First Oral Lyme Disease Prevention Drug

A new clinical trial is testing a potential preventative treatment for Lyme disease, the most common vector-borne illness in the US. Tarsus Pharmaceuticals has begun dosing participants in its Phase 2 Calliope trial for TP-05, an oral medication designed to kill Lyme-infected ticks before they transmit the disease. If successful, it could become the first FDA-approved prophylactic option for those at risk. Lyme disease affects an estimated 300,000 to 400,000 Americans each year, with over 90% of cases concentrated in the Northeast and upper Midwest. States like Connecticut, New York, Pennsylvania, and Wisconsin report the highest numbers. Without treatment, the disease can lead to severe, long-term health problems.

TP-05, also known as lotilaner, has shown promise in early studies. Preclinical tests in mice found it 90% effective in preventing Lyme disease, compared to no protection in untreated animals. A Phase 2a trial (Carpo) also demonstrated that TP-05 killed over 90% of attached ticks within 24 hours. The Calliope trial will assess the drug's safety, tolerability, and pharmacokinetics in around 700 healthy adults at risk of Lyme disease. Tarsus plans to finish enrolment during the 2026 tick season, with key results expected by early 2027.

Currently, no FDA-approved medication exists to prevent Lyme disease. If TP-05 proves effective, it could offer a new way to protect the more than 35 million Americans at moderate to high risk. The trial's outcome may determine whether the drug moves closer to regulatory approval.