BioSpace: ArmaGen CEO: Phase II Data Shows Cognitive Improvement in Juvenile Hurler Syndrome Patients

By Alex Keown

SAN DIEGO — Enzyme replacement therapy drug Aldurazyme provided a lifeline for many children diagnosed with Hurler syndrome, a mucopolysaccharide disease. Lives of patients were extended by years. Now, an experimental therapy developed by tiny ArmaGen, is providing a boost to the cognitive abilities of those patients.

ArmaGen’s treatment is AGT 181, a novel enzyme replacement therapy for the treatment of both somatic and cognitive symptoms in patients with Hurler syndrome, also known as MPS I. This week the company is presenting interim data from a Phase II study of 13 patients that shows four of five patients who have completed a 26-week regimen showed a significant improvement in cognitive function, as well as motor skill development.

Mathias Schmidt, chief executive officer of Calabasas, Calif.-based ArmaGen, told BioSpace in an exclusive interview that he was excited about the findings. Today the company presented its findings at the 13th annual WORLDSymposium in San Diego. Schmidt said the findings show the company is on the right track in “putting action into hope.”

That’s a phrase that Schmidt keeps close to his heart. During a meeting with Hurler families, Schmidt said the mother of one patient told him she wished her child had cancer, because then there would be more hope.

“Hope is a terrible word until we turn hope into action,” Schmidt said.

MPS I is a rare, hereditary, lysosomal storage disease that arises from a deficiency or absence of the enzyme iduronidase, which is needed to break down complex sugars produced by the body. MPS I affects approximately 3,000 to 4,000 patients worldwide. The most severe form of Hurler syndrome affects the brain and spinal cord in children, resulting in medical and cognitive challenges that can include developmental delay, progressive mental decline, loss of physical function, impaired language development, airway obstruction, corneal and retinal damage, carpal tunnel syndrome and restricted joint movement

ArmaGen, which has 15 fulltime employees, developed AGT-181 by re-engineering the enzyme iduronidase as a fusion protein with an immunoglobulin G (IgG) antibody targeting the insulin receptor. Using its proprietary “Trojan Horse” technology, AGT-181 takes advantage of the body’s natural system for transporting proteins and other large molecules non-invasively across the blood-brain barrier (BBB), in this case by binding the same receptor that transports insulin across the BBB into the brain, according to company information.

When ArmaGen’s information was presented this morning by Roberto Giugliani, the physician leading the clinical trials, Schmidt said he wants Hurler parents to be a signal to that the company is “trying to put that hope into action.”

At the meeting, ArmaGen’s data indicated AGT-181 was responsible for improvements in neurological and cognitive function in four of five patients, as well as stabilization of neurological and cognitive function in the fifth patient. While some of the patients had severe cognitive impairments, Schmidt said the experimental therapy was responsible for significant improvements. For example, one nine-year-old patient had the cognitive ability equivalent to a newborn, but after treatment, the patient showed cognitive growth that was comparable to a nine month old. A 15-year-old patient taking the therapy saw a doubling of his abilities, which Schmidt said was an amazing improvement, especially considering the greater difficulty in the treatment crossing the blood-brain barrier at later ages. Although the patients are still significantly impaired, he said the growth they have shown is “a big victory.”

“Can you imagine what their parents are feeling to see this kind of growth?” he asked.

Also, ArmaGen’s data shows AGT-181 was similarly efficacious somatically, meaning the drug also stimulated positive results in the skeletal structure of the patients. Many MPS I patients have orthopedic issues, such as weak bones or hip dysplasia. Schmidt said standard enzyme replacement therapy does not treat the orthopedic issues, but data is showing that AGT-181 is having some kind of effect. That will have to be further studied, he said, but it provides additional support that ArmaGen is on the right track to treat the genetic disorder.

Schmidt said findings are still preliminary, but highly encouraging. He added that the drug and its Trojan Horse delivery method means there are additional disease indications it could be used to treat, including Rett Syndrome. He said this could “literally open a floodgate” to many other CNS diseases, including Parkinson’s disease, Alzheimer’s disease and multiple sclerosis.

Coming out of the WORLDSymposium, Schmidt said he hopes the data will not only be encouraging for Hurler syndrome families, but also for potential partners who might want to work with ArmaGen and help take the trial into a critical Phase III.

“We need to stay honest and sincere with the message that we still have to go a long way to go before we get it (AGT-181) into the market and make it available to patients,” Schmidt said.

Here is a link to the original article published on