JCR Pharmaceuticals Co., Ltd. announced the completion of enrollment in its global Phase III clinical trial for JR-141 (pabinafusp alfa), a groundbreaking enzyme replacement therapy designed to address the neurological symptoms of mucopolysaccharidosis type II (MPS II), commonly known as Hunter syndrome. The trial, designated JR-141-GS31, is currently ongoing across the United States, Latin America, and Europe.
Novel Blood-Brain Barrier Technology
JR-141 represents a significant advancement in treating Hunter syndrome by incorporating JCR's proprietary J-Brain Cargo technology, which enables the therapy to cross the blood-brain barrier and deliver treatment directly to the central nervous system. The drug is a recombinant fusion protein combining an antibody against the human transferrin receptor with iduronate-2-sulfatase, the enzyme that is missing or malfunctioning in patients with Hunter syndrome.
"This achievement is a milestone in the JR-141 clinical development program, as the Hunter syndrome community needs a therapy that treats the cognitive symptoms of this devastating and life-threatening disease for which there are inadequate treatment options available," said Shin Ashida, Chairman, President and CEO of JCR Pharmaceuticals.
Addressing Unmet Medical Needs
Hunter syndrome is an X-linked recessive lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase, an enzyme responsible for breaking down complex carbohydrates called glycosaminoglycans in the body. The condition affects an estimated 2,000-3,000 individuals worldwide and manifests through a wide range of somatic and neurological symptoms. While enzyme replacement therapy serves as the current standard of care, central nervous system symptoms related to MPS II have remained an unmet medical need.
Mechanism of Action and Clinical Evidence
JR-141 crosses the blood-brain barrier through transferrin receptor-mediated transcytosis, with cellular uptake mediated through the mannose-6-phosphate receptor. This novel mechanism of action specifically targets the central nervous system symptoms of Hunter syndrome, which traditional enzyme replacement therapies cannot address due to their inability to penetrate the blood-brain barrier.
In non-clinical trials, JCR confirmed high-affinity binding of pabinafusp alfa to transferrin receptors and demonstrated passage across the blood-brain barrier into neuronal cells. The company also verified enzyme uptake in various brain tissues and confirmed reduction of substrate accumulation in both the central nervous system and peripheral organs in animal models of Hunter syndrome.
Clinical studies have provided evidence of the therapy's effectiveness, including reduction of heparan sulfate concentrations in cerebrospinal fluid, a biomarker for assessing effectiveness against central nervous system symptoms. These clinical results were consistent with pre-clinical study findings and demonstrated positive effects on CNS symptoms.
Regulatory Milestone and Global Expansion
In March 2021, Japan's Ministry of Health, Labour and Welfare approved JR-141, marketed under the brand name IZCARGO, for lysosomal storage disorders. This approval marked JR-141 as the first-ever enzyme replacement therapy worldwide capable of penetrating the blood-brain barrier.
The completion of Phase III enrollment represents a critical step toward potential global regulatory approvals. Ashida expressed optimism about the trial's progress, stating, "We are making good progress in this global Phase III clinical trial, and we look forward to sharing the clinical data as they are available."
Company Profile and Pipeline
JCR Pharmaceuticals is a global specialty pharmaceutical company with a 50-year legacy in Japan, now expanding its footprint into the United States, Europe, and Latin America. The company's approved products in Japan include therapies for growth disorder, MPS II, Fabry disease, acute graft-versus host disease, and renal anemia.
The company's investigational pipeline focuses on rare diseases, with products in development for MPS I (Hurler, Hurler-Scheie and Scheie syndrome), MPS II, and MPS IIIA and B (Sanfilippo syndrome type A and B), among others. JCR's approach combines scientific expertise with unique technologies to develop next-generation therapies for complex healthcare challenges.
