Sanfilippo B enzyme replacement therapy wins orphan drug status
JR-446 is designed to deliver absent alpha-N-acetylglucosaminidase enzyme
The U.S. Food and Drug Administration (FDA) has granted orphan drug status to JR-446, JCR Pharmaceuticals’ brain-penetrating experimental enzyme replacement therapy (ERT) for Sanfilippo syndrome type B, the company has announced.
The designation is meant to accelerate the clinical development and review of investigational therapies with the potential to treat rare conditions. It provides regulatory support and financial incentives, including seven-year market exclusivity, if a drug is approved.
The treatment’s safety and efficacy are being tested in a Phase 1/2 trial (NCT06488924), which may still be enrolling people with Sanfilippo syndrome type B in Japan.
“This orphan drug designation supports the potential of this therapy to address the significant unmet medical need of patients with MPS IIIB,” Shin Ashida, JCR’s president, chairman, and CEO, said in a company press release.
Sanfilippo syndrome type B, also called mucopolysaccharidosis (MPS) type IIIB, is caused by the absence or reduced activity of the alpha-N-acetylglucosaminidase enzyme due to mutations in the NAGLU gene. This leads to the complex sugar molecule heparan sulfate accumulating to toxic levels inside cells.
Nerve cells in the central nervous system (CNS), which includes the brain and spinal cord, are especially sensitive to heparan sulfate buildup, which leads to nerve cell damage and death, and contributes to symptoms such as sleep disturbances, loss of speech, and behavioral changes.
Enzyme replacement therapy for Sanfilippo type B involves delivering the faulty or missing enzyme to patients, which should slow or prevent disease progression. Enzymes cannot naturally cross the blood-brain barrier (BBB), the protective membrane that prevents microbes and large molecules from entering the CNS, however.
Delivering the missing enzyme to BBB
JR-446, developed in partnership with Medipal Holdings, is composed of an alpha-N-acetylglucosaminidase fused to an antibody that binds to a BBB transporter called the transferrin receptor using JCR’s proprietary J-Brain Cargo technology.This way, the therapy can cross the BBB and increase the enzyme’s levels and activity in the CNS.
“We will continue the development of JR-446 in collaboration with JCR so that we can soon deliver this drug to the patients and their families who are desperately waiting, as there is currently no treatment available,” said Shuichi Watanabe, Medipal’s representative director, president, and CEO.
The trial is expected to include 10 children and adolescents, up to age 17, who’ll receive JR-446 by infusion into a vein, or intravenously. Its main goals are to evaluate how well the treatment is tolerated, specifically by monitoring the frequency and severity of infusion-related reactions, and to assess its effectiveness at reducing heparan sulfate in the cerebrospinal fluid, which surrounds and protects the brain and spinal cord, over up to four years. The treatment’s pharmacological properties and efficacy at improving cognitive function are also being assessed.
Medipal and JCR entered a license agreement in 2023, wherein Medipal is supporting the development of JR-446 in Japan, including its clinical trial advancement, drug distribution, and disease awareness. Medipal will also commercialize JR-446 outside Japan.
JCR also used its BBB-penetrating technology to develop JR-441 for Sanfilippo syndrome type A. The company is recruiting children and teens with Sanfilippo type A for a Phase 1/2 trial (NCT06095388) in Germany.
