Sanfilippo B therapy JR-446 gets orphan drug status in Europe
JCR's enzyme replacement therapy has similar status in U.S.
The European Commission has granted orphan drug status to JR-446, a brain-penetrating enzyme replacement therapy (ERT) for Sanfilippo syndrome type B.
The designation, announced in a press release from developer JCR Pharmaceuticals, is aimed at accelerating the clinical development and review of investigational therapies that have the potential to treat rare conditions. It provides regulatory support and financial incentives, including 10-year market exclusivity, if a drug is approved.
JR-446 was recently granted orphan drug status by the U.S. Food and Drug Administration. Its safety and efficacy are being tested in a Phase 1/2 trial (NCT06488924), which may still be recruiting patients in Japan.
Sanfilippo syndrome type B, also known as mucopolysaccharidosis type IIIB, is caused by mutations in the NAGLU gene that result in the absence or reduced activity of the alpha-N-acetylglucosaminidase enzyme. The enzyme breaks down a complex sugar molecule called heparan sulfate. When missing, this molecule accumulates to toxic levels inside cells.
Nerve cells in the central nervous system (CNS, the brain and spinal cord) are particularly sensitive to heparan sulfate buildup, which leads to nerve cell damage and death. This contributes to Sanfilippo symptoms, which may include sleep disturbances, loss of speech, and behavioral changes.
Crossing the blood-brain barrier
Enzyme replacement therapy, in which a working version of the missing enzyme is delivered to patients, is being explored as a potential treatment to slow disease progression. However, enzymes cannot naturally cross the blood-brain barrier, a protective layer of cells that prevents microbes and large molecules from entering the CNS, and reach their target cells.
JR-446, developed in collaboration with Medipal Holdings, consists of a functional alpha-N-acetylglucosaminidase enzyme fused to an antibody targeting the transferrin receptor, a key transporter that facilitates crossing of molecules across the blood-brain barrier.
The therapy, created using JCR’s proprietary J-Brain Cargo technology, can cross the blood-brain barrier and increase the enzyme’s levels and activity in the CNS. According to the company, animal studies have demonstrated that JR-446 effectively penetrates the central nervous system and significantly reduces heparan sulfate accumulation.
The ongoing Phase 1/2 trial is expected to include 10 children and adolescents, up to age 17, with Sanfilippo syndrome type B, who will receive JR-446 by intravenous (into the vein) infusion for up to four years.
The trial’s main goals are to evaluate how well the treatment is tolerated, by monitoring the frequency and severity of infusion-related reactions, and to assess its effectiveness at reducing heparan sulfate in the cerebrospinal fluid that surrounds and protects the CNS.
Secondary measures include assessing JR-446’s pharmacological properties and its efficacy at improving participants’ cognitive function.
JCR also used its technology to develop JR-441 for Sanfilippo syndrome type A, which is currently being tested in a Phase 1/2 trial (NCT06095388) that’s recruiting children and teenagers at a site in Germany.
