First Sanfilippo syndrome type A patient dosed with JR-441 ERT
Phase 1 clinical trial will test therapy as once-weekly infusion in children, teens
A Phase 1 clinical trial in Japan that’s testing JCR Pharmaceuticals‘ experimental enzyme replacement therapy JR-441 for treating Sanfilippo syndrome type A has dosed its first patient.
The study will test the therapy as a once-weekly infusion into the bloodstream in children and adolescents, ages 1-18 to assess its safety and biological effects, along with its pharmacokinetics, which are a drug’s movement into, through, and out of the body. No other details about the study were provided by the company.
The announcement follows the trial’s clearance by the Pharmaceuticals and Medical Devices Agency, a regulatory agency in Japan, in September.
“We have been eagerly awaiting the opportunity to offer this treatment, and I am hopeful that its effectiveness will be confirmed in the clinical setting, ultimately improving the daily lives of both patients and their families,” Kimitoshi Nakamura, MD, professor of pediatrics at Kumamoto University and the trial’s medical expert, said in a company press release.
Sanfilippo syndrome type A, the most common type of the condition, is a genetic disorder caused by mutations in the SGSH gene, which provides the instructions for cells to make heparan N-sulfatase, an enzyme that breaks down heparan sulfate, a large sugar molecule.
As a result of these mutations, heparan sulfate builds up inside cells of the brain and spinal cord, leading to symptoms such as developmental delays, behavioral problems, and cognitive impairment. There is no approved treatment for this rare condition.
How would JR-441 work in Sanfilippo syndrome type A?
JR-441 is designed to deliver a working version of heparan N-sulfatase to the brain. It uses proprietary J-Brain Cargo technology, which combines the enzyme with an antibody that binds to the transferrin receptor, a protein used to get iron through the blood-brain barrier, a tightly interlocked layer of cells that protects the brain from harmful substances, like bacteria and toxins, circulating in the blood. The barrier often prevents medications from reaching the brain, where they can treat neurological conditions, however.
By hijacking the transferrin receptor transport system, JR-441 can get into the brain, which should reduce heparan sulfate in nerve cells, easing the disease’s symptoms.
“This novel therapeutic approach represents a new era for managing the condition,” Nakamura said.
JR-441 is also being tested in a Phase 1/2 trial (NCT06095388) taking place at a site in Germany. The study is enrolling about 12 Sanfilippo type A patients, ages 1-18, who will receive the therapy weekly at a low or high dose.
The first patient was dosed last year and the study’s main goal is to test the treatment’s safety and tolerability for up to five years. Researchers will also assess if JR-441 improves cognitive function and reduces heparan sulfate in the blood, urine, and cerebrospinal fluid that surrounds the brain and spinal cord.
JR-441 has received orphan drug status by the U.S. Food and Drug Administration and the European Commission. These designations are intended to accelerate a therapy’s clinical development and review, and grant several years of market exclusivity if regulatory approval is granted.
