In short
Pegtibatinase is an investigational enzyme therapy being studied for classical homocystinuria (HCU), a rare inherited condition caused by cystathionine beta synthase deficiency. Two clinical trials are registered for pegtibatinase: a Phase 1/2 study with 15 participants and a Phase 3 study with 70 participants. Both trials use subcutaneous injection and focus on lowering plasma total homocysteine (tHcy) levels in people receiving standard of care.
Key points
- Pegtibatinase is an investigational enzyme therapy for classical homocystinuria due to cystathionine beta synthase deficiency.
- The Phase 3 trial compares pegtibatinase against placebo in 70 participants aged 12 to 65 years.
- A Phase 1/2 study evaluated safety and tolerability in 15 participants, including a pediatric cohort.
- Both trials measure plasma total homocysteine (tHcy) levels as a key outcome.
- Pegtibatinase is given by subcutaneous injection at a dose of 2.5 mg/kg in the Phase 3 trial.
- Both registered trials are currently in Authorised status in the EU registry.
What is pegtibatinase?
Pegtibatinase is an investigational enzyme therapy being developed for classical homocystinuria (HCU), a rare inherited metabolic disorder caused by deficiency of the enzyme cystathionine beta synthase (CBS). The substance is a pegylated form of an enzyme designed to replace or supplement the missing CBS activity. Pegtibatinase is not yet authorised as a medicine; it remains under investigation in clinical trials.
How does pegtibatinase work?
In classical homocystinuria, the enzyme cystathionine beta synthase does not work properly, which leads to a build-up of the amino acid homocysteine in the blood. Pegtibatinase is designed to break down homocysteine, thereby lowering plasma total homocysteine (tHcy) levels. The Phase 3 trial measures the change from baseline in plasma tHcy levels averaged over weeks 6 through 12 as its primary outcome. The Phase 1/2 study also assessed changes in methionine levels and the incidence of hypermethioninemia and hypomethioninemia.
Which conditions is it studied for?
- Classical homocystinuria (HCU) — a rare inherited condition caused by cystathionine beta synthase deficiency, leading to high levels of homocysteine in the blood. Both registered trials study pegtibatinase in this condition.
How is pegtibatinase given?
Pegtibatinase is given by subcutaneous injection. In the Phase 3 trial, the dose used is 2.5 mg/kg. The Phase 1/2 study evaluated dose-related safety and tolerability of subcutaneous pegtibatinase across multiple cohorts, including a pediatric open-label cohort. The placebo arm in the Phase 3 trial uses 0.9% sodium chloride saline solution.
What do the clinical trials show?
Which phases and what status do the trials have?
Two trials are registered. One is a Phase 3 study comparing pegtibatinase with placebo in 70 participants. The other is a Phase 1/2 study in 15 participants, with a double-blind treatment period (cohorts 1–6) and a pediatric open-label treatment period (cohort 7). Both trials are listed as Authorised in the EU registry.
Who can take part in these trials?
The Phase 3 trial enrols participants aged 12 to 65 years with classical homocystinuria due to cystathionine beta synthase deficiency who are receiving standard of care treatment. The Phase 1/2 study included adult participants in cohorts 1–6 and a pediatric cohort (cohort 7) in an open-label period.
What are the trials measuring?
The Phase 3 trial primarily measures the change from baseline in plasma total homocysteine (tHcy) levels averaged over weeks 6 through 12, comparing pegtibatinase with placebo. The Phase 1/2 study measured safety and tolerability outcomes, including adverse events, clinical laboratory findings, electrocardiogram parameters, and the presence of anti-pegtibatinase and anti-polyethylene glycol (PEG) antibodies.
What side effects are known?
The registered trial records do not report specific side effect frequencies. The Phase 1/2 study collected data on adverse events by type, severity, and relationship to study drug, as well as immunogenicity measures such as anti-pegtibatinase antibodies and anti-PEG antibodies. No supplementary sources describing known side effects were provided.