Findings from a phase 1 clinical trial conducted in patients with primary biliary cholangitis (PBC) have demonstrated that treatment with TH104—a transmucosal buccal film that incorporates the active ingredient nalmefene—is safe and tolerable.
A press release from Tharimmune—manufacturer of the agent, and a biotechnology company devoted to development of a portfolio of therapeutic agents for immunology and immunology—showed that TH104 exhibited the ability to suppress the chronic, debilitating pruritus or uncontrollable itching frequently associated with PBC.
Individuals with the chronic autoimmune disorder PBC can experience a myriad of debilitating symptoms, including fatigue and the unrelenting itching of pruritus. In fact, pruritus, which is known to be a common clinical manifestation observed in hepatic disorders, is especially common in cholestatic liver disease.
It was recently reported that patients with PBC who experience pruritus are often undertreated. In survey data obtained from individuals with PBC and pruritus, respondents have described their itch as the feeling of “bugs crawling under the skin.”
TH104 has been described as a “proprietary transmucosal buccal film embedded with the approved, active compound nalmefene[,] which easily adheres inside of the mouth on the cheek and biodegrades within minutes.” This is a key finding, since it has been recognized that TH104 is designed to avoid the first-pass metabolism of the liver—an event that occurs when a drug is administered orally, enters the liver, then experiences extensive biotransformation to an extent in which the bioavailability of the agent becomes dramatically decreased.
The phase 1, single-center, single-dose, randomized, open-label, two-way crossover trial compared treatment with TH104 16 mg and intravenously (IV) administered nalmefene 1 mg under fasting conditions. There was a seven-day washout period that occurred between the doses.
Read more about PBC signs and symptoms
According to the study protocol, a total of 16 participants were scheduled and prespecified to complete both doses used in the crossover design, based on the study protocol. Additionally, 20 healthy normal volunteers participated in the analysis, 19 of whom completed the study.
The primary objectives of the trial were to assess the absolute bioavailability of TH104, and to evaluate the tolerability and safety of the agent. This phase 1 pharmacokinetic trial is ongoing, with complete data anticipated to be available in the second quarter of 2024.
Results of the study showed that TH104 had a comparable safety and tolerability profile to the U.S. Food and Drug Administration–approved nalmefene reference IV formulation of the agent. All of the adverse events (AEs) that were reported in the study, which were deemed to be mild in nature, were reported uniformly between the IV injectable formulation and TH104.
No deaths, serious AEs, or other significant AEs were reported during the entire study period, with any AEs consistent with those reported in the literature, such as drowsiness, dizziness, and self-resolving nausea.
According to Randy Milby, Chief Executive Officer of Tharimmune, “We are pleased with the completion of our [p]hase 1 study of TH104[,] and our expectations for a safe and tolerable transmucosal film delivery have been met. We would like to thank the [t]rial subjects for participating in this program . . . [We] remain on-track to initiate a [p]hase 2 program this year,” he concluded.
