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 3 development for the treatment of classical homocystinuria (HCU). Classical HCU is a rare metabolic disorder characterized by elevated levels of plasma 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. 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.

In December 2021, the Company announced positive topline results through the first five cohorts of the Phase 1/2 COMPOSE Study, showing that treatment with pegtibatinase at a dose of 1.5 mg/kg BIW resulted in rapid and sustained reductions in tHcy through 12 weeks of treatment. In May 2023, the Company announced positive results in the sixth cohort, showing that treatment with pegtibatinase at a dose of  2.5 mg/kg BIW resulted in a mean relative reduction from baseline of 67.1% (n=4, mean baseline tHcy = 96.8 μM), compared to a 0.6% increase in tHcy levels from baseline for patients receiving placebo in the study (n=6, mean baseline tHcy = 124.8 μM), as well as maintenance of mean tHcy below the clinically meaningful threshold of 100 μM, over weeks 6 to 12. To date in the study, pegtibatinase has been generally well-tolerated. In December 2023, the Company announced the initiation of the Phase 3 HARMONY Study of pegtibatinase for the treatment of classical homocystinuria. Read the press release>