Travere's HARMONY trial for HCU pushes primary completion 20 months to 2027
The Phase 3 readout the company once flagged for 2026 now depends on a trial that shifted its own completion target and returned to active recruiting.
Executive Summary
- The trial's own completion date has moved by roughly a year and a half, and the sponsor's most recent public guidance now points to a later readout than what was repeated in earlier disclosures.
- A status change back to active recruitment alongside the completion-date shift signals that data collection is still underway rather than nearing a close.
- This program stands as the only Phase 3 test of its mechanism in this disease, with no in-class precedent to gauge what a positive result should look like.
- Multiple rare-disease and expedited designations already in place point to unmet need in classical HCU, and set up a defined efficacy bar the trial's biomarker endpoint must clear.
The catalyst
Travere Therapeutics is developing pegtibatinase, an enzyme replacement therapy, in the pivotal Phase 3 HARMONY trial for classical homocystinuria (HCU), a rare metabolic disorder caused by cystathionine beta synthase deficiency. The trial is testing pegtibatinase against placebo on top of standard-of-care treatment in patients ages 12 to 65, with a primary endpoint of change from baseline in plasma total homocysteine (tHcy) levels measured between weeks 6 and 12. The company had guided toward a data readout in calendar year 2026 across four disclosures issued between January and August 2024. NCT06247085+1A Study to Investigate Efficacy and Safety of Pegtibatinase Compared With Placebo in Participants ≥12 to ≤65 Years of Age With Classical Homocystinuria (HCU) Due to Cystathionine Beta Synthase Deficiency Receiving Standard of Care TreatmentNCT06247085Travere Therapeutics Provides Corporate Update and 2024 OutlookJan 8, 2024
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
The completion-date shift
The registry record for NCT06247085 shows the primary completion date moved from December 1, 2025 to August 1, 2027, a change logged on May 8, 2026. On the same date, the trial's status reverted from Active, not recruiting back to Recruiting, having first switched to Active, not recruiting on November 6, 2024. Travere's own first-quarter 2026 disclosure now points to topline HARMONY data in the second half of 2027, a later window than the calendar-2026 guidance the company had repeated through mid-2024. The trial has logged one primary-completion-date change since its initial registration and carries a Stable protocol-stability label, reflecting a single amendment cycle rather than repeated churn. NCT06247085+1A Study to Investigate Efficacy and Safety of Pegtibatinase Compared With Placebo in Participants ≥12 to ≤65 Years of Age With Classical Homocystinuria (HCU) Due to Cystathionine Beta Synthase Deficiency Receiving Standard of Care TreatmentNCT06247085Travere Therapeutics Provides Corporate Update and 2024 OutlookJan 8, 2024
Enrollment and design
HARMONY targets 70 participants, unchanged from its original registered target, with no enrollment growth flagged by the operational model against typical Phase 3 thresholds for this design. The trial enrolls patients with a screening plasma tHcy of at least 80 micromoles per liter, with an allowance for up to 18 participants enrolled between 50 and 80 micromoles per liter. The study spans 52 facilities across 14 countries, including the United States, several European Union member states, the United Kingdom, Australia, Turkey, Qatar and Saudi Arabia. NCT06247085A Study to Investigate Efficacy and Safety of Pegtibatinase Compared With Placebo in Participants ≥12 to ≤65 Years of Age With Classical Homocystinuria (HCU) Due to Cystathionine Beta Synthase Deficiency Receiving Standard of Care TreatmentNCT06247085
The competitive frame
Pegtibatinase and its sibling long-term extension study, NCT06431893, are the only two Phase 3 assets registered against Homocysteine in classical HCU, and both are Travere programs. A second-generation candidate from Aeglea Biotherapeutics, pegtarviliase, targets the same disorder but sits in Phase 1/2 testing, leaving pegtibatinase as the only Phase 3 entrant. No competitor trial in this target-indication pair has completed or terminated, so there is no resolved outcome from a peer program to benchmark HARMONY's eventual result against. NCT06247085A Study to Investigate Efficacy and Safety of Pegtibatinase Compared With Placebo in Participants ≥12 to ≤65 Years of Age With Classical Homocystinuria (HCU) Due to Cystathionine Beta Synthase Deficiency Receiving Standard of Care TreatmentNCT06247085
The regulatory backdrop
Pegtibatinase carries Fast Track, Breakthrough Therapy, and Rare Pediatric Disease designations from the FDA, plus Orphan Drug designation in both the United States and the European Union, each announced by Travere on September 26, 2024. Those designations mark classical HCU as a disease with unmet treatment need under FDA and EU frameworks, and they do not by themselves indicate how the trial's biomarker endpoint will read out. The trial's biochemical endpoint, change in plasma tHcy, is the metric regulators and the sponsor have identified as central to establishing pegtibatinase as what the company has called a first disease-modifying therapy for the condition. TravereTravere Therapeutics Provides Corporate Update and 2024 OutlookJan 8, 2024
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.