Travere Therapeutics Pauses Phase 3 HARMONY Study Enrollment for Pegtibatinase Manufacturing Scale-Up

Travere Therapeutics, Inc. (Nasdaq: TVTX) has announced a voluntary pause in the enrollment of new patients for its Phase 3 HARMONY Study, which is evaluating the efficacy of pegtibatinase as a treatment for classical homocystinuria (HCU). The pause aims to address necessary improvements in the manufacturing scale-up to support commercial production, while ensuring that current patients in the study continue to receive their medication as planned.

Currently enrolled participants will not be impacted by this pause and will continue receiving their medication from existing small-scale production batches. The decision to halt new enrollments was made after the company found that the desired drug substance profile was not achieved in the recent scale-up process. Travere is in the process of notifying all study investigators about this decision and will resume enrollment once additional material becomes available.

Dr. Bill Rote, senior vice president of research and development at Travere Therapeutics, stated, "We believe in the potential for pegtibatinase to become the first disease-modifying therapy for classical HCU. Our team is committed to making the necessary improvements in our manufacturing processes to continue this pivotal program. We will support current trial participants while optimizing our commercial-scale manufacturing process."

Travere expects to evaluate the required commercial process improvements with an anticipated restart of enrollment in the Phase 3 HARMONY Study slated for 2026. This delay will push previously planned investments related to clinical enrollment and large-scale production past 2025. With the anticipated reduction in costs associated with the development of sparsentan as its Phase 3 programs near completion, the company estimates a reduction in research and development expenses by more than $30 million in 2025 compared to 2024. Travere believes its existing cash, cash equivalents, and marketable securities, totaling $325.4 million as of June 30, 2024, will support its operations until 2028.

Classical homocystinuria (HCU) is a rare genetic disorder caused by a deficiency in the enzyme cystathionine beta synthase (CBS), leading to toxic levels of homocysteine. This can result in severe complications such as stroke, pulmonary embolism, deep vein thrombosis, as well as developmental delays and skeletal complications. Current treatment options are limited and primarily involve dietary restrictions and vitamin supplements.

Pegtibatinase is an investigational enzyme replacement therapy designed to target the underlying cause of classical HCU. Preclinical studies have shown that pegtibatinase can reduce total homocysteine levels and improve clinical outcomes. The Phase 3 HARMONY Study aims to evaluate the efficacy and safety of pegtibatinase through a global, randomized, multi-center, double-blind, placebo-controlled trial. In previous studies, pegtibatinase demonstrated a significant reduction in homocysteine levels and was generally well-tolerated over 12 weeks of treatment. The program has received multiple designations from the FDA, including Breakthrough Therapy, Rare Pediatric Disease, and Fast Track, as well as Orphan Drug designation in the U.S. and Europe.

Travere Therapeutics is dedicated to developing therapies for rare diseases. The company collaborates closely with the rare disease community to identify, develop, and deliver life-changing treatments. Travere emphasizes its commitment to understanding patient perspectives and aims to provide hope through innovative therapies.

Travere Therapeutics will host a conference call and webcast today at 4:30 p.m. ET to discuss the voluntary pause in the HARMONY Study enrollment. Participating in the call requires dialing +1 (323) 994-2093 (U.S.) or +1 (888) 394-8218 (International), with the confirmation code 5880214. The webcast can be accessed on Travere’s Investor page, and an archived version will be available for 30 days post-call.