Date: 2014-12-11
Type of information: Presentation of results at a congress
phase: 1-2
Announcement: presentation of results at the 14th International Symposium on MPS and Related Diseases in Bonn,
Company: Armagen (USA - CA)
Product: AGT-182
Action
mechanism: enzyme replacement therapy (ERT)/fusion protein. AGT-182 is an investigational enzyme replacement therapy (ERT) for the treatment of Hunter syndrome. AGT-182 is a human insulin receptor monoclonal antibody-fused iduronate 2-sulfate designed to cross the blood brain barrier (BBB) through the insulin receptors present on the BBB. ArmaGen entered into a worldwide licensing and collaboration agreement with Shire in 2014 which could include potential payments of up to $225 million to develop AGT-182 for the treatment of both the central nervous system (CNS) and somatic (body-related) manifestations of Hunter syndrome. Under the terms of the agreement, ArmaGen will receive R&D funding, development and sales milestones, and future royalties from Shire.
Disease: mucopolysaccharidosis II (MPS II, Hunter Syndrome)
Therapeutic area: Rare diseases - Genetic diseases
Country: USA
Trial
details: The Breaking Barriers trial is an open-label, sequential, multi-dose study designed to determine a safe and well-tolerated dose of AGT-182, a compound that utilizes the body’s natural system for transporting products across the blood-brain barrier by targeting the receptor that delivers insulin to all cells of the body, including the brain. Its ability to cross the BBB makes AGT-182 unique among potential treatments for Hunter syndrome.This trial is a sequential, open-label, dose escalation, multi-dose study in adults with Hunter syndrome. At least two dose levels, assuming tolerability, are planned sequentially, with safety data from the previous cohort being reviewed prior to escalation to the next higher dose cohort. Following a minimum washout period of at least 6 weeks for subjects on ERT, subjects will receive weekly doses of AGT-182 for 8 weeks. (NCT02262338)
Latest
news: * On July 14, 2016, ArmaGen announced the presentation of data from the first cohort of adult patients (n=4) enrolled in the Phase 1/2a Breaking Barriers clinical trial of AGT-182, an investigational enzyme replacement therapy (ERT) for the treatment of Hunter syndrome. The data, presented at MPS 2016, the 14th International Symposium on MPS and Related Diseases in Bonn, Germany, show that in a small (n=4) cohort, a weekly 1.0-mg/kg dose of AGT-182, administered as an intravenous (IV) infusion to attenuated Hunter patients, was generally well-tolerated. Based on a review of the available safety, clinical, and bioanalytical data, an independent Data Monitoring Committee (DMC) has recommended proceeding to the study’s second cohort, in which adult patients are to receive a weekly IV infusion starting at a dose of 3 mg/kg. As with the first cohort, patients enrolled in the second cohort will be age 18 and over.
At MPS 2016, Patrice Rioux, M.D., Ph.D., presented data from four adult male patients with Hunter syndrome who received weekly IV infusions of AGT-182. Measurements taken at week eight showed clinically significant decreases in liver and spleen volumes in two of the four patients. Levels of urinary glycosaminoglycans (GAGs), a marker for the disease, also showed clinically significant decreases in four of the four patients.
The investigators observed transient decreases in gluose levels (blood glucose levels <70 mg/dL) in all patients but did not consider these episodes clinically significant. Other adverse events (AEs) possibly related to AGT-182 included anxiety, headache, throat itchiness, lightheadedness, nausea, jitters, clammy hands, and weakness. AEs unlikely related to AGT- 182 included mild leg cramps, leg pain, sleep disturbances, hip pain, decreased endurance, fatigue, abodominal rash, emesis prior to dose start, cough, headache, back pain, neck pain, and migraine.
* On December 11, 2014, ArmaGen announced that the Investigational New Drug (IND) application for the company’s lead product candidate, AGT-182 for the treatment of Hunter syndrome, has been accepted by the FDA and is now active. This will enable ArmaGen to initiate a Phase 1 clinical trial, which is expected to begin in the first quarter of 2015, to assess the safety and tolerability of AGT-182 in adult male patients with Hunter syndrome. AGT-182 is designed to utilize the body’s natural system for transporting products across the blood-brain barrier (BBB) by targeting the receptor that delivers insulin to all cells of the body.
As previously announced, ArmaGen entered into a worldwide licensing and collaboration agreement with Shire plc valued at $225 million to develop AGT-182 for the treatment of both the central nervous system (CNS) and somatic (body-related) manifestations of Hunter syndrome. ArmaGen is responsible for conducting the Phase 1 study of AGT-182.
