Travere pumps brakes on late-stage enzyme replacement therapy study, citing production scale-up problems

Shortly after winning full FDA approval for its rare kidney disease drug Filspari, San Diego’s Travere Therapeutics has run into trouble with its enzyme replacement candidate pegtibatinase.

Travere is pausing enrollment in its Harmony study evaluating pegtibatinase in classic homocystinuria (HCU) to make improvements on manufacturing scale-up for commercial production and to fully enroll the phase 3 trial.

Travere made the decision to pump the brakes on the study after it found that the desired drug substance profile for pegtibatinase was not achieved during its recent scale-up process, the company said in a press release Thursday.

Travere is working to inform study investigators of its decision and doesn’t expect Harmony to restart enrollment until at least 2026 as it weighs commercial process improvements for the late-stage program.

The silver lining is that patients currently enrolled in pegtibatinase studies will continue to receive the drug from “small scale batches which are unaffected by the scale-up process,” Travere said. Those patients will be able to continue on the study medication for the duration of the trials they’re taking part in, Travere added.

Travere’s study had been looking to recruit 70 patients. It’s unclear how many patients had been enrolled prior to the recruitment pause, analysts at Evercore ISI wrote in a note to clients Friday morning.

The analysts also noted that the trial will remain blinded during the pause, meaning the data from the first cohort using smaller batches of product can be collected for Travere’s eventual approval submission. The Everecore team cautioned that that may not remain true if the larger batches fail to meet certain expectations to be considered the same product as the smaller ones.

Pegtibatinase is being tested in HCU, a rare genetic disorder that affects the body’s ability to process the amino acid homocysteine. The disorder can cause the amino acid to build up to harmful levels in the blood and urine, leading to complications involving the eyes, skeletal system, central nervous system and vascular system.

With the trial pause on pegtibatinase and as Filspari nears the end of its clinical journey, Travere said it expects research and development costs in 2025 to be about $30 million lower versus 2024. As of June 30, Travere had $325.4 million on hand, which it says should keep the company afloat into 2028.

The manufacturing hiccup comes as Travere’s Filspari continues its forward momentum.

In early September, the drug (also known as sparsentan) converted its accelerated nod in the kidney disease IgA nephropathy (IgAN) into a full FDA approval. As part of the decision, the FDA removed a specific urine protein level requirement from Filspari’s label, opening up the drug to any patient at risk of disease progression.

Filspari won its initial accelerated nod in early 2023 on phase 3 data showing it could significantly cut protein in the urine compared to irbesartan after 36 weeks of treatment.

Filspari’s launch has been progressing nicely so far. The medicine generated $27.1 million in second-quarter sales, marking a 37% increase over the sum it brought down for the prior quarter.