JCR’s Phase 1/2 trial of JR-441 for Sanfilippo A doses 1st patient

Trial still recruiting children ages 1-18 at single site in Germany

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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JCR Pharmaceuticals is now recruiting children and adolescents with Sanfilippo syndrome type A for a Phase 1/2 clinical trial testing its enzyme replacement therapy JR-441 at a single location in Hamburg, Germany.

The first patient in the trial recently was dosed, according to a press release from JCR.

The trial (NCT06095388), which is enrolling up to 12 patients, ages 1 to 18, with a confirmed diagnosis of Sanfilippo type A, was given the green light by regulatory authorities in Germany earlier this year.

“This disease has no established standard of care and enrollment in this study offers [patients] access to an experimental interventional treatment,” said Nicole Muschol, MD, the trial’s principal investigator.

In a notice on its website, the Cure Sanfilippo Foundation noted that eligible patients will weigh at least 10 kilograms (about 22 pounds). Participants will be randomly assigned to receive weekly intravenous or into-the-vein infusions of either a low or high dose of JR-441.

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The trial’s main goal is to see how safe and well tolerated JR-441 is for up to five years from the first dose. It also will measure the therapy’s blood levels and pharmacokinetics — a drug’s movement into, through, and out of the body — as secondary measures.

Other secondary measures include changes in heparan sulfate levels in the cerebrospinal fluid, the liquid that surrounds the brain and spinal cord, as well as in the blood and urine. Changes in cognitive function also will be assessed.

Sanfilippo syndrome type A, also known as mucopolysaccharidosis type IIIA, occurs due to mutations in SGSH, a gene that codes for an enzyme called heparan N-sulfatase. This enzyme breaks down heparan sulfate, a large sugar molecule.

Without a working version of this enzyme, heparan sulfate builds up in cells in the body, mainly in the brain and spinal cord, causing delays in development, challenges in behavior, and impaired cognition or intellectual disability. Symptoms usually arise in early childhood and worsen over time.

JR-441 is designed to deliver a working version of heparan N-sulfatase to the brain. It uses proprietary J-Brain Cargo technology to combine the enzyme with an antibody that binds to transferrin receptor, a protein that is used for getting iron through the blood-brain barrier.

This barrier is a tightly interlocked layer of cells that protect the brain against harmful substances, such as bacteria and toxins, but also can keep medications from reaching the brain, where they may be needed.

By hijacking the transferrin receptor transport system, JR-441 can get across and into the brain. This is expected to reduce heparan sulfate levels in the brain and spinal cord, thereby easing the symptoms of Sanfilippo syndrome.

“JR-441 is the third program based on the J-Brain Cargo platform that enters clinical stage,” said Shin Ashida, chairman, president and CEO of JCR, calling it “another testament to our efforts to bring our innovation to patients across the globe.”

“My deepest respect goes to the families, Dr. Muschol and all the physicians and clinical staff who are so committed to changing the future of individuals affected with this disease,” Ashida said.

In early 2022, JR-441 was granted orphan drug designation in Europe for the treatment of Sanfilippo syndrome type A. The designation is meant to speed the therapy’s clinical development and review process by offering regulatory support and financial benefits.