Travere Therapeutics has announced a voluntary pause in enrollment for its Phase 3 HARMONY study, which is evaluating pegtibatinase for the treatment of classical homocystinuria (HCU). The decision, announced on September 26, 2024, stems from challenges encountered during the manufacturing scale-up process necessary for commercial production.
The company determined that the desired drug substance profile was not achieved in the recent scale-up, prompting the enrollment pause. Travere is actively informing study investigators about the decision to halt new patient enrollment until the manufacturing issues are resolved.
Impact on Clinical Development and Financial Outlook
The company anticipates that the earliest date to restart enrollment in the Phase 3 HARMONY Study will be in 2026. Planned investments related to clinical enrollment in HARMONY and large-scale production are expected to be delayed beyond 2025. However, Travere projects that research and development expenses may be reduced by more than $30 million in 2025 compared to 2024, partially offset by the expected decline in costs associated with the development of sparsentan as its Phase 3 programs advance towards completion.
According to Travere, its existing cash, cash equivalents, and marketable securities of $325.4 million as of June 30, 2024, are expected to support operations into 2028.
Continued Commitment to Current Patients
Bill Rote, Ph.D., senior vice president of research and development at Travere Therapeutics, emphasized the company's commitment to patients currently enrolled in pegtibatinase studies. "We remain committed to supporting the patients currently enrolled in our clinical trials while working with our manufacturing partners to optimize our commercial-scale manufacturing process," Rote stated.
Patients currently enrolled in pegtibatinase studies will continue to receive study medication from small-scale batches unaffected by the scale-up process. These patients will be able to continue their treatment schedules for the duration of their participation in the trials.
About Classical Homocystinuria and Pegtibatinase
Classical HCU is a rare genetic metabolic disorder caused by a deficiency in the enzyme cystathionine beta synthase (CBS). This deficiency leads to toxic levels of homocysteine, potentially resulting in life-threatening thrombotic events, ophthalmologic and skeletal complications, and developmental delay. Current treatment options are limited to protein-restricted diets and the use of vitamin B6 and betaine.
Pegtibatinase is an investigational PEGylated, recombinant enzyme replacement therapy designed to address the underlying cause of classical HCU. It has received Breakthrough Therapy designation, Rare Pediatric Disease and Fast Track designations by the FDA, as well as Orphan Drug designation in the U.S. and Europe.
