JCR Pharmaceuticals Completes Enrollment in Global Phase III Trial for JR-141 Targeting Hunter Syndrome
JCR Pharmaceuticals Co., Ltd. (TSE 4552; JCR) has announced the successful completion of participant enrollment for its global Phase III clinical trial of JR-141 (pabinafusp alfa), a groundbreaking therapy currently under development for the treatment of mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome. The pivotal study, designated JR-141-GS31, is being conducted across multiple regions, including the United States, Latin America, and Europe.
JR-141 is a recombinant fusion protein combining an antibody targeting the human transferrin receptor with iduronate-2-sulfatase—the enzyme deficient in individuals with Hunter syndrome. The therapy is built on JCR’s proprietary J-Brain Cargo® platform, a novel blood-brain barrier (BBB)-penetrating technology designed to enable therapeutic proteins to cross into the central nervous system (CNS), addressing the neurological manifestations of MPS II that have historically been difficult to treat.
Innovation at the Blood-Brain Barrier
One of the central challenges in treating Hunter syndrome has been delivering therapies effectively to the brain. While existing enzyme replacement therapies (ERTs) can address peripheral symptoms, they typically fail to cross the BBB, leaving cognitive symptoms untreated.
JCR’s J-Brain Cargo® platform aims to overcome this limitation. In preclinical studies, JR-141 demonstrated strong binding affinity to transferrin receptors and successful translocation across the BBB into neuronal cells. Once inside the brain, the enzyme component of JR-141 was shown to be absorbed by target tissues, reducing the pathological accumulation of glycosaminoglycans in both the CNS and peripheral organs.
Clinical evidence has reinforced these findings. Multiple trials of JR-141 have revealed reductions in cerebrospinal fluid (CSF) heparan sulfate levels—a biomarker for CNS symptom burden in Hunter syndrome. These biochemical improvements have been accompanied by encouraging signs of clinical benefit in cognitive function and other neurological outcomes.
Addressing an Urgent Medical Need
Hunter syndrome is a rare, inherited lysosomal storage disorder caused by a deficiency in iduronate-2-sulfatase, an enzyme involved in the degradation of glycosaminoglycans (GAGs), which accumulate in tissues and organs over time. The disease primarily affects males and is estimated to impact 2,000 to 3,000 individuals globally.
The clinical manifestations of MPS II are broad and debilitating, ranging from physical abnormalities and organ dysfunction to profound neurological impairment. While current ERTs can help alleviate somatic symptoms, they do not penetrate the CNS, leaving cognitive decline largely untreated—an unmet need that JR-141 is specifically designed to address.
“This achievement is a significant milestone in the JR-141 clinical development program,” said Shin Ashida, Chairman, President and CEO of JCR Pharmaceuticals. “The Hunter syndrome community urgently needs a therapy that can address the cognitive decline associated with this devastating disease. With this trial progressing globally, we are committed to bringing JR-141 closer to those who need it. We extend our deepest gratitude to the participants and their families.”
Regulatory Milestones and Global Outlook
JR-141 has already achieved notable regulatory success. In March 2021, Japan’s Ministry of Health, Labour and Welfare (MHLW) approved JR-141 under the brand name IZCARGO® for the treatment of MPS II. This approval marked a global first: the only enzyme replacement therapy granted regulatory clearance for its ability to cross the BBB and potentially treat the neurological symptoms of a lysosomal storage disorder.
The current Phase III trial aims to further validate these benefits across a broader, international patient population. By focusing on both biochemical and clinical endpoints, JCR is striving to demonstrate the therapy’s impact on functional outcomes and overall quality of life for individuals with Hunter syndrome.
About JR-141 (Pabinafusp Alfa)
JR-141 is a fusion protein composed of a monoclonal antibody targeting the human transferrin receptor and iduronate-2-sulfatase. It utilizes a dual-receptor uptake mechanism: it crosses the BBB through transferrin receptor-mediated transcytosis and is taken up into cells via the mannose-6-phosphate receptor pathway. This dual action allows JR-141 to exert its therapeutic effects on both central and peripheral symptoms of Hunter syndrome.
Preclinical and clinical data have consistently shown reductions in CSF heparan sulfate levels, corresponding with improvements in CNS symptoms such as cognitive decline and behavioral disturbances. These results suggest that JR-141 has the potential to become a transformative therapy for MPS II patients with neurological involvement.
