Potential for pegtibatinase to become first disease-modifying treatment for classical HCU; topline data expected in 2026

SAN DIEGO, CA, USA I December 14, 2023 I Travere Therapeutics, Inc. (Nasdaq: TVTX) today announced the Company has opened enrollment in the HARMONY Study, a global, randomized pivotal Phase 3 clinical trial of pegtibatinase, a novel investigational enzyme replacement therapy being evaluated for the treatment of classical homocystinuria (HCU). Classical HCU is a rare genetic metabolic disorder caused by a deficiency in the enzyme cystathionine beta synthase (CBS). The study is designed to determine the safety and efficacy of pegtibatinase in reducing plasma total homocysteine (tHcy) levels, a key treatment goal in classical HCU, compared to placebo in participants who are receiving standard of care.

“Classical HCU is a devastating rare disease that often manifests in childhood and can lead to serious complications due to toxic levels of homocysteine. These complications include continuous risk of developing life-threatening thrombotic events, such as heart attack and stroke, skeletal abnormalities, cognitive developmental delays, and intellectual disabilities. Patients and caregivers have limited treatment options, including adherence to highly restrictive diets that often are very challenging to follow and inadequate for maintaining metabolic control of homocysteine levels,” said William Rote, Ph.D., senior vice president of research and development at Travere Therapeutics. “The initiation of the HARMONY Study is an exciting step forward in addressing this significant unmet need and advancing our goal to deliver pegtibatinase as the first disease-modifying treatment option for the classical HCU community.”

The HARMONY Study is a global, randomized, multi-center, double-blind, placebo-controlled Phase 3 clinical trial designed to evaluate the efficacy and safety of pegtibatinase as a novel treatment to reduce tHcy levels. The trial is expected to enroll approximately 70 patients (≥12 to ≤65 years of age at screening) with a diagnosis of classical HCU who continue to have tHcy levels ≥50 μM while maintaining their standard-of-care treatment. Participants will be randomized 1:1 to receive 2.5 mg/kg of pegtibatinase or placebo, administered subcutaneously, for a 24-week blinded treatment duration. The primary endpoint is relative geometric mean change in plasma tHcy levels from baseline compared to weeks 6 through 12, and durability of treatment response through 24 weeks of treatment will be measured as a secondary endpoint. The Company expects topline data from the HARMONY Study to become available in 2026. The Company will also be initiating the ENSEMBLE Study, a Phase 3b, open-label, long-term extension, that will evaluate the ongoing efficacy and long-term safety of pegtibatinase in participants with HCU following their completion of the Phase 1/2 COMPOSE Study or the Phase 3 HARMONY Study. The ENSEMBLE Study will include an optional protein tolerance modification sub-study that will evaluate if eligible patients can increase their natural dietary protein intake while maintaining an acceptable level of metabolic control while receiving pegtibatinase.  

The initiation of the Phase 3 HARMONY Study is based on the positive safety and efficacy data from the Phase 1/2 COMPOSE Study. In COMPOSE, pegtibatinase demonstrated dose-dependent reductions in tHcy during 12 weeks of treatment. At the 2.5 mg/kg dose, pegtibatinase provided rapid and sustained reductions in tHcy, with a 67.1% mean relative reduction in tHcy from baseline, as well as maintenance of mean tHcy below the clinically meaningful threshold of 100 μM, over weeks 6 to 12. To date in the COMPOSE Study, pegtibatinase has been generally well-tolerated.

Pegtibatinase has been granted Breakthrough Therapy, Rare Pediatric Disease and Fast Track designations by the U.S. Food and Drug Administration (FDA), as well as Orphan Drug designation in the U.S. and Europe.

About Classical Homocystinuria

Classical homocystinuria (HCU) is a rare genetic metabolic disorder caused by a deficiency in the enzyme cystathionine beta synthase (CBS). CBS is a pivotal enzyme that is essential for the management of methionine and cysteine in the body. Classical HCU leads to toxic levels of homocysteine that can result in life-threatening thrombotic events such as stroke, pulmonary embolism and deep vein thrombosis, ophthalmologic and skeletal complications, as well as developmental delay. Current treatment options are limited to protein-restricted diet and use of vitamin B6 and betaine.

About Pegtibatinase

Pegtibatinase is an investigational PEGylated, recombinant enzyme replacement therapy designed to address the underlying cause of classical homocystinuria (HCU). In preclinical studies, pegtibatinase has demonstrated an ability to reduce total homocysteine levels and improve clinical parameters. Pegtibatinase is currently advancing in the ongoing Phase 1/2 COMPOSE Study to assess its safety, tolerability, pharmacokinetics, pharmacodynamics and clinical effects in patients with classical HCU. In May 2023, the Company announced that data from four patients treated with the highest dose of pegtibatinase showed a clinically meaningful 67.1% mean relative reduction in total homocysteine from baseline and was generally well-tolerated after 12 weeks of treatment. To date, the pegtibatinase program has been granted 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.

About Travere Therapeutics

At Travere Therapeutics, we are in rare for life. We are a biopharmaceutical company that comes together every day to help patients, families and caregivers of all backgrounds as they navigate life with a rare disease. On this path, we know the need for treatment options is urgent – that is why our global team works with the rare disease community to identify, develop and deliver life-changing therapies. In pursuit of this mission, we continuously seek to understand the diverse perspectives of rare patients and to courageously forge new paths to make a difference in their lives and provide hope – today and tomorrow. For more information, visit travere.com

SOURCE: Travere Therapeutics