pegtibatinase (TVT-058) / Travere Therap - LARVOL DELTA

Pegtibatinase: An Investigational Enzyme Replacement Therapy in Development for Treatment of Classical Homocystinuria (SSIEM 2026) - "Sponsored by Travere Therapeutics"

Metabolic Disorders

Pegtibatinase as a Treatment for Patients With Classical Homocystinuria (HCU) (Also Known as the COMPOSE Study) (clinicaltrials.gov) - P1/2 | N=39 | Recruiting | Sponsor: Travere Therapeutics, Inc. | Active, not recruiting ➔ Recruiting | Trial completion date: Dec 2026 ➔ Jul 2027 | Trial primary completion date: Jun 2026 ➔ Jul 2027

Enrollment open • Trial completion date • Trial primary completion date • Metabolic Disorders

A Long-term Extension Study to Assess the Long-term Safety and Efficacy of Pegtibatinase Treatment in Participants ≥5 to ≤65 Years of Age With Classical Homocystinuria (HCU) (ENSEMBLE) (clinicaltrials.gov) - P3 | N=100 | Enrolling by invitation | Sponsor: Travere Therapeutics, Inc. | Trial completion date: Jan 2027 ➔ Aug 2030 | Trial primary completion date: Jan 2027 ➔ Aug 2030

Trial completion date • Trial primary completion date • Metabolic Disorders

HARMONY: A 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 Treatment (clinicaltrials.gov) - P3 | N=70 | Recruiting | Sponsor: Travere Therapeutics, Inc. | Active, not recruiting ➔ Recruiting | Trial completion date: Jan 2026 ➔ Sep 2027 | Trial primary completion date: Dec 2025 ➔ Aug 2027

Enrollment open • Trial completion date • Trial primary completion date • Metabolic Disorders

TVTX-TVT058-301: A study to investigate efficacy and safety with pegtibatinase compared to placebo in participants ?12?to??65?years of age with classical homocystinuria (HCU) due to cystathionine beta synthase deficiency receiving standard of care treatment (clinicaltrialsregister.eu) - P2/3 | N=8 | Not yet recruiting | Sponsor: Travere Therapeutics Inc.

New P2/3 trial • Metabolic Disorders

Pegtibatinase, an Investigational Enzyme Replacement Therapy, for the Treatment of Classical Homocystinuria (HCU): Design of the HARMONY Phase 3 Study (ACMG 2026) - P1/2 | "HARMONY is a global Phase 3 registrational clinical trial that will evaluate the safety and efficacy of pegtibatinase in participants with HCU who have tHcy levels ≥50 μM despite receiving current standard-of-care treatments."

P3 data • Genetic Disorders • Metabolic Disorders

Homocystinuria: Advances in metabolic and molecular therapies targeting homocysteine pathways (Review). (PubMed, Mol Med Rep) - "Enzyme replacement therapies such as pegtibatinase, pegtarviliase and CDX‑6512 have shown promise in preclinical and early clinical studies, achieving notable homocysteine reduction. The present review summarizes these emerging therapeutic strategies, highlighting their potential to correct metabolic imbalances in HCU, improve clinical outcomes, and address the limitations of both conventional and novel treatments. The present review also incorporates novel epidemiological findings, integrates the foundational enzymology of HCU with current genotype‑phenotype associations and updates the therapeutic landscape through early 2025 with key developments such as the discontinuation of the pegtarviliase program and the rebranding of CDX‑6512 as SYNT‑202."

Journal • Review • Alzheimer's Disease • Cardiovascular • Cognitive Disorders • Gene Therapies • Metabolic Disorders • Transplantation • MTHFR

COMPOSE Phase 1/2 Clinical Trial: Pegtibatinase Data Update (SSIEM 2023) - "Sponsored by Travere"

Clinical • P1/2 data • Metabolic Disorders

Pegtibatinase, an Investigational Enzyme Replacement Therapy for the Treatment of Classical Homocystinuria (HCU): Latest Findings from the COMPOSE Phase 1/2 Trial (SSIEM 2023) - P1/2 | "One patient had substantial reduction in methionine, requiring addition of natural protein to the diet. Discussion These results demonstrate the potent treatment effect of pegtibatinase on tHcy reduction and support its further development as a novel therapy for HCU."

P1/2 data • Dermatology • Genetic Disorders • Immunology • Metabolic Disorders • Urticaria • Vascular Neurology

Pegtibatinase: An Investigational Enzyme Replacement Therapy in Development for Treatment of Classical Homocystinuria (SSIEM 2023) - "Sponsored by Travere"

Metabolic Disorders

Safety and efficacy of pegtibatinase enzyme replacement therapy in adults with classical homocystinuria in the COMPOSE® phase 1/2 randomized trial. (PubMed, Genet Med) - P1/2 | "Pegtibatinase was generally well tolerated and substantially reduced tHcy levels, demonstrating potential as a treatment for HCU."

Journal • P1/2 data • Dermatology • Immunology • Metabolic Disorders • Urticaria

Travere Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "Net product sales of FILSPARI totaled $50 million in 4Q 2024; $132 million for full year 2024....The FDA assigned a PDUFA target action date of August 28, 2025, to the Company’s supplemental New Drug Application (sNDA) requesting modification of liver monitoring for FILSPARI in IgAN....The Company’s partner, Renalys Pharma, Inc., recently completed enrollment in its registrational Phase 3 clinical trial of sparsentan for the treatment of IgAN in Japan and expects topline results in the second half of 2025....Pegtibatinase (TVT-058) – Classical HCU: The Company is continuing to make progress on the necessary process improvements in manufacturing scale-up and is on track to restart enrollment in the Phase 3 HARMONY Study in 2026."

Enrollment status • P3 data: top line • PDUFA • Sales • IgA Nephropathy • Metabolic Disorders • Rare Diseases

HARMONY: A 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 Treatment (clinicaltrials.gov) - P3 | N=70 | Active, not recruiting | Sponsor: Travere Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metabolic Disorders

COMPOSE® PHASE 1/2, DOSE-ESCALATION COHORT 7 DESIGN: SAFETY OF PEGTIBATINASE IN CHILDREN AGED ≥5–<12 YEARS WITH CLASSICAL HOMOCYSTINURIA (HCU) (SSIEM 2024) - P1/2 | "Discussion/ConclusionCohort 7 is a new cohort in the COMPOSE® Phase 1/2 trial with a novel design that will assess safety and efficacy of pegtibatinase as a potential novel treatment in pediatric participants aged ≥5 to <12 years with HCU. Palavras-chave : Homocystinuria, Pegtibatinase, Enzyme replacement therapy, Homocysteine, Pediatric"

Clinical • P1/2 data • Metabolic Disorders • Ophthalmology • Pediatrics

PEGTIBATINASE, AN INVESTIGATIONAL ENZYME REPLACEMENT THERAPY FOR CLASSICAL HOMOCYSTINURIA (HCU): DESIGN OF THE HARMONY AND ENSEMBLE PHASE 3 STUDIES (SSIEM 2024) - P1/2, P3 | "Pegtibatinase is being advanced in two global Ph3 studies, HARMONY and ENSEMBLE, to provide the basis for establishing its safety and efficacy as a potential novel treatment for HCU."

P3 data • Metabolic Disorders

ENSEMBLE: A Phase 3 Long-term Extension Study to Assess the Long-term Safety and Efficacy of Pegtibatinase Treatment in Participants ≥12 to ≤65 Years of Age With Classical Homocystinuria (HCU) (clinicaltrials.gov) - P3 | N=90 | Enrolling by invitation | Sponsor: Travere Therapeutics, Inc.

New P3 trial • Metabolic Disorders