Pegtibatinase is an investigational therapeutic candidate for the treatment of classical homocystinuria

Pegtibatinase is a novel investigational human enzyme replacement candidate being evaluated in Phase 1/2 development for the treatment of classical homocystinuria (HCU). Classical HCU is a rare metabolic disorder characterized by elevated levels of plasma homocysteine that can lead to vision, skeletal, circulatory and central nervous system issues. Learn more about classical HCU.

Patient Need

Current treatment options for people with classical HCU, including severe dietary restrictions and use of vitamin B6 and betaine, are often ineffective in managing homocysteine levels and a significant unmet need remains.

Our Approach

Pegtibatinase is an investigational PEGylated, recombinant enzyme replacement candidate designed to address the underlying cause of classical HCU — a deficiency in the naturally occurring enzyme cystathionine beta synthase (CBS). The goal of the pegtibatinase program is to develop a well-tolerated, safe and effective treatment that sustainably replaces CBS activity to reduce levels of homocysteine.

Clinical Trials

Pegtibatinase is currently advancing in a Phase 1/2 dose escalation study to assess its safety, tolerability, pharmacokinetics, pharmacodynamics and clinical effects in patients with classical HCU. Pegtibatinase has been granted Breakthrough Therapy, Rare Pediatric Disease and Fast Track designations by the FDA, as well as Orphan Drug designation in the US and Europe.

On December 15, 2021, Travere announced positive topline results from the ongoing Phase 1/2 COMPOSE Study of pegtibatinase. In the highest dose cohort to date evaluating 1.5mg/kg of pegtibatinase twice weekly (BIW), treatment with pegtibatinase resulted in rapid and sustained reductions in total homocysteine (tHcy) through 12 weeks of treatment, including a 55.1% mean relative reduction in tHcy from baseline as well as maintenance of tHcy below a clinically meaningful threshold of 100 μmol. To date in the study, pegtibatinase has been generally well-tolerated.

Travere is preparing to engage with regulators to establish next steps for a pivotal development program to ultimately support the potential approvals of pegtibatinase for the treatment of classical HCU. The company has also initiated one additional cohort in the COMPOSE study to further inform our understanding of pegtinatinase.


View the press release here