JR-441 enzyme replacement therapy named orphan drug by FDA

ERT being tested in Phase 1/2 trial in Germany for Sanfilippo type A

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by Andrea Lobo |

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An experimental enzyme replacement therapy (ERT), called JR-441, for Sanfilippo syndrome type A has been designated an orphan drug by the U.S. Food and Drug Administration, the treatment’s developer, JCR Pharmaceuticals, has announced.

The designation is given to therapies being developed for conditions affecting fewer than 200,000 people in the U.S. It provides incentives to accelerate clinical development and review, including eligibility for tax credits for clinical trials, exemption from application fees, and the potential for seven years marketing exclusivity in the U.S. if a therapy is approved.

“There are currently no treatment options for patients with [Sanfilippo syndrome type A],” Shin Ashida, JCR’s chairman and president, said in a press release. “We look forward to advancing JR-441 in clinical development and bringing this very important treatment to patients … as quickly and safely as possible.”

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SGSH gene mutations lead to reduced activity of heparan N-sulfatase enzyme

Sanfilippo syndrome type A, also known as mucopolysaccharidosis type IIIA, is caused by mutations in the SGSH gene that lead to no or reduced activity of the heparan N-sulfatase enzyme, which is required to break down a complex sugar molecule called heparan sulfate.

This results in the toxic accumulation of heparan sulfate, particularly inside nerve cells of the central nervous system (CNS, comprising the brain and spinal cord), leading to neurodegeneration and disease symptoms.

Symptoms include developmental delay, behavioral and cognitive issues, and intellectual disability, usually starting during early childhood and worsening over time.

Currently, treatments work to ease symptoms to improve quality of life. However, several therapies are under development — including ERTs, which involve the delivery of the crucial enzyme to patients — that are expected to slow disease progression.

JR-441 is designed to effectively cross the blood-brain barrier, which is a protective cell layer that prevents harmful molecules but also some medications from entering the CNS. JCR’s proprietary technology, called J-Brain Cargo, allows the therapy to enter the CNS by fusing the heparan N-sulfatase enzyme to an antibody that binds to the transferrin receptor, a protein that is used for getting iron through the blood-brain barrier.

The therapy is being tested in a Phase 1/2 trial (NCT06095388) involving up to 12 Sanfilippo type A patients, ages 1 to 18, at a single site in Germany. The first patient received the treatment in October.

The trial’s main goal is to test JR-441’s safety and tolerability for up to five years. Secondary measures include the therapy’s pharmacological properties and changes in heparan sulfate levels in the blood, urine, and cerebrospinal fluid, or the liquid that surrounds the CNS. Changes in the patient’s cognitive function will also be evaluated.

The therapy was granted orphan drug designation by the European Commission in January 2022.