ArmaGen reports preliminary evidence of cognitive improvement in children with MPS I treated with AGT-181 

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ArmaGen reports preliminary evidence of cognitive improvement in children with MPS I treated with AGT-181 

Initial Results from Phase 2 Proof-of-Concept Trial Presented at 2017 WORLDSymposium

Findings Demonstrate Ability of ArmaGen’s Proprietary Drug Delivery Technology to Transport Biopharmaceuticals Across the Blood-Brain Barrier

ArmaGen, Inc., a privately held biotechnology company focused on developing groundbreaking therapies to treat severe neurological disorders, has reported preliminary evidence of cognitive improvement in children treated with AGT-181, the company’s investigational therapy for the treatment of Hurler and Hurler-Scheie syndrome (also known as mucopolysaccharidosis type I, or MPS I). The initial results from an ongoing Phase 2 proof-of-concept (POC) study, presented at the 13th annual WORLDSymposium in San Diego, California, suggest that AGT-181 may improve cognitive function in patients with MPS I, demonstrating the ability of ArmaGen’s proprietary drug delivery technology to transport biopharmaceuticals across the blood-brain barrier.

In an oral presentation entitled, “Intravenous infusion of iduronidase-IgG and its impact on the central nervous system in children with Hurler syndrome,” Roberto Giugliani, M.D., Ph.D., of Hospital de Clínicas in Porto Alegre, Brazil, reported improvements in neurological and cognitive function in four of five patients, and stabilization of neurological and cognitive function in the fifth patient. He also noted that AGT-181 was similarly efficacious somatically (related to the rest of the body other than the brain) to currently available enzyme replacement therapy (ERT) and displayed a favorable safety and tolerability profile.

“Existing enzyme replacement therapies improve many somatic manifestations of Hurler syndrome, but they do not address the severe and progressive neurological symptoms, as they do not cross the blood-brain barrier,” explained Dr. Giugliani. “While our findings are still preliminary, we are satisfied with the safety profile of AGT-181 and encouraged by the indications of potential improvement in cognitive markers from neuropsychological tests conducted with MPS I children treated with AGT-181. We hope to further confirm these results as the study continues.”

At the WORLDSymposium, Dr. Giugliani presented up to 26 weeks of data from the first five children with MPS I (age 2 years or older) enrolled in the 6-month study. All five patients had previously been treated with standard ERT, and one had received a stem cell transplant which had failed engraftment. Once enrolled, the children received weekly intravenous infusions of AGT-181 at doses of 1.0 or 3.0 mg/kg. Developmental age-appropriate neurocognitive testing was conducted at 13 and 26 weeks of treatment, utilising either the Bayley Scales of Infant Development III; or the Kaufman Assessment Battery for Children. Together, the two tests (commonly abbreviated as B-K) represent a summation of scores from cognitive, language and motor skills.

Four of the five patients demonstrated improvement in their B-K cognitive score domain, and the patient who had failed engraftment after stem cell transplantation showed stabilisation in this domain. Somatic disease control under AGT-181 was similar to what is commonly observed under standard ERT, based on stabilisation of urinary glycosaminoglycan (GAG) levels and either stabilisation or reduction in liver and/or spleen volume. Additionally, a trend towards improvement in shoulder range of motion was observed.

“Successful delivery of biotherapeutics across the blood-brain barrier is a goal that has eluded the entire pharmaceutical industry for decades,” said Mathias Schmidt, Ph.D., chief executive officer of ArmaGen. “We are therefore extremely gratified to see clinical data that indicate ArmaGen’s proprietary ‘Trojan horse’ technology can deliver the missing enzyme into the CNS of patients and modulate cognitive function. Beyond MPS, the technology has immense potential utility in other CNS disorders, and we are excited about exploring these opportunities in further research. The ArmaGen staff wants to cordially thank the patients and their parents for engaging in this study.”

Drug-related adverse events (AEs) in the Phase 2 POC trial included two infusion site reactions and two hypoglycemic events that were transient and well controlled by glucose administration. No serious AEs were observed that were likely to be drug-related.


Read the full press release on the ArmaGen website.