Aeglea BioTherapeutics, Inc. says dosing in the third cohort of the phase 1/2 clinical trial of pegtarviliase for the treatment of classical homocystinuria is under way.
Patients in this cohort are receiving 1.35 mg/kg of pegtarviliase once weekly administered via subcutaneous injection; patients in cohorts 1 and 2 received doses of 0.15 mg/kg and 0.45 mg/kg, respectively.
Additionally, Aeglea BioTherapeutics received a letter from the U.S. Food and Drug Administration (FDA) responding to a recently submitted protocol amendment for the phase 1/2 clinical trial of pegtarviliase for the treatment of classical homocystinuria.
The protocol amendment, among other things, requested the inclusion of adolescent patients at clinical trial sites in the U.S. The FDA stated the protocol did not provide adequate justification and evidence to support the prospect of direct clinical benefit for pediatric patients and placed the trial on partial clinical hold for the enrollment of patients less than 18 years of age under this investigational new drug (IND) at this time.
Aeglea BioTherapeutics said it intends to address the feedback from the FDA and aims to satisfy the requirements for prospective benefit for future inclusion of pediatric patients under the IND, including in a potential pivotal trial.
The company believes the letter will have no impact on the planned enrollment and dosing of patients aged 18 years and older in the U.S. or patients aged 12 years and older in the U.K. and Australia. Enrollment in the trial remains on track and Aeglea BioTherapeutics continues to expect to announce data in the fourth quarter of 2022, including data from cohort 3.
The primary endpoint of the phase 1/2 open-label trial is safety and tolerability. Three to four patients will be enrolled in each cohort and treated with four once weekly doses of pegtarviliase.
About pegtarviliase in homocystinuria
Pegtarviliase (formerly AGLE-177) is a novel recombinant human enzyme, which is engineered to degrade the amino acid homocysteine and its dimer. Pegtarviliase is currently being studied in a phase 1/2 clinical trial for the treatment of patients with classical homocystinuria, a rare inherited disorder of methionine metabolism that results in elevated levels of total homocysteine.
Homocysteine accumulation plays a key role in multiple progressive and serious disease-related complications, including thromboembolic vascular events, skeletal abnormalities (including severe osteoporosis), developmental delay, intellectual disability, lens dislocation and severe near sightedness.
In preclinical studies, pegtarviliase improved important disease-related abnormalities and survival in a mouse model of homocystinuria. Pegtarviliase has received both U.S. and EU Orphan Drug Designation as well as U.S. Rare Pediatric Disease Designation.