Travere halts Phase 3 inherited disease trial due to manufacturing scale-up issue

Travere Therapeutics said there is a “voluntary pause” in recruitment to its Phase 3 study in a rare, inherited disorder due to issues in scaling up its production process. The company said enrollment won’t likely resume until 2026 at the earliest.

The San Diego biotech added Thursday that its scale-up did not reach the “desired drug substance profile” it was going after for its recombinant enzyme replacement therapy, dubbed pegtibatinase. The candidate is under investigation for classical homocystinuria, a condition where patients cannot metabolize certain amino acids due to an enzyme deficiency.

Bill Rote

Travere will work with its manufacturing partners to “optimize” its commercial-scale manufacturing process, R&D chief Bill Rote said in a statement.

The placebo-controlled Phase 3 HARMONY study, which started enrollment in December 2023, was designed to enroll 70 patients. In the trial’s blinded treatment period, there is a two-week dose-titration portion, followed by a 22-week blinded assessment, according to ClinicalTrials.gov.

Wall Street analysts have said that topline data from the late-stage trial could be delayed by two years to 2028, with the company previously saying results should be expected in 2026. Travere added Thursday that large-scale production for the asset is also going to be delayed past 2025.

Patients already enrolled in the Phase 3 will continue taking pegtibatinase that has been manufactured in different batches unaffected by the scale-up issues. The enrolled patients will continue taking pegtibatinase for the length of the study. Travere is in the process of notifying study investigators.

Although the trial delay is a setback for Travere, analysts have said this is a “minor” one considering much of the attention on the company is on its autoimmune disease drug Filspari, particularly its market rollout. Filspari secured full approval in IgA nephropathy earlier this month.

Due to the HARMONY study delay, the company expects its R&D expenses to be reduced by more than $30 million in 2025 compared to this year.