Japan agency clears JR-441 trial for Sanfilippo syndrome type A
JCR Pharmaceuticals says Japan’s PMDA OKs Phase 1 study
JCR Pharmaceuticals said it received permission from the Pharmaceuticals and Medical Devices Agency (PMDA), a regulatory agency in Japan, to start a Phase 1 clinical trial of JR-441, an experimental enzyme replacement therapy for Sanfilippo syndrome type A.
The company didn’t provide details.
“We are pleased that the PMDA’s review of the Phase I study plan is complete, and that clinical development program is progressing,” Shin Ashida, JCR’s chairman and president, said in a press release. “We are committed to continuing to advance the JR-441 clinical development program with the goal of meeting the unmet medical needs of this patient community.”
Sanfilippo syndrome type A, or mucopolysaccharidosis (MPS) III A, is caused by mutations in the SGSH gene. The enzyme it encodes, heparan N-sulfatase, works to break down a large sugar molecule called heparan sulfate.
As a result of these mutations, heparan sulfate accumulates to toxic levels inside cells of the central nervous system (the brain and spinal cord), leading to symptoms including developmental delays, behavioral issues, and impaired cognition.
‘Dire need’ to treat neurological symptoms
Sanfilippo syndrome type A is “a rare and life-threatening lysosomal storage disorder for which there are currently no approved treatment options,” and there’s a “dire need to address the neurological signs and symptoms” of the disease, Ashida said.
JR-441 is designed to deliver a functional form of the missing enzyme using JCR’s J-Brain Cargo technology, in which the enzyme is combined with an antibody that binds to the transferrin receptor.
By binding to this receptor, the therapy can cross the blood-brain barrier, a membrane that prevents harmful molecules, but also some medications, from entering the brain. JR-441 is expected to reduce heparan sulfate levels in nerve cells and ease symptoms.
The therapy is being tested in a Phase 1/2 trial (NCT06095388) enrolling an estimated 12 Sanfilippo type A patients, ages 1 to 18, at a single site in Germany. Eligible patients must weigh at least 10 kilograms (about 22 pounds) and will receive weekly intravenous (into-the-vein) infusions of either a low dose or high dose of JR-441.
The first patient started treatment last year. The trial’s main goal is to test the treatment’s safety and tolerability for up to five years. Secondary measures include JR-441’s pharmacological properties, changes in heparan sulfate levels in the blood, urine, and cerebrospinal fluid, the liquid that surrounds the brain and spinal cord, and changes in cognitive function.
JR-441 has been awarded orphan drug designation by the U.S. Food and Drug Administration and the European Commission. The designation aims to accelerate the therapy’s clinical development and review, and offers certain incentives, including a period of market exclusivity if the treatment is ultimately approved.
