Japanese company, JCR Pharmaceuticals, has received an orphan drug designation from the European Commission for their Sanfilippo type A drug candidate JR-441. This orphan designation will enable the further development of JR-441 in the European Union. The company has plans to prepare for a global clinical trial with JR-441 in patients with Sanfilippo type A to start in 2023.
JR-441 is an enzyme replacement therapy (ERT) utilising JCR’s J-Brain Cargo® BBB-penetrating technology. This form of ERT can cross the blood-brain barrier to deliver sulfamidase, the enzyme deficient in Sanfilippo type A, to where it is most needed.
In other ERT-based clinical trials for Sanfilippo, the enzyme has been unable to cross the blood-brain barrier if it is delivered into the bloodstream. Instead, the enzyme has been delivered via direct injection into the fluid surrounding the brain or the spinal canal to target the neurological aspects of the disease. However, this can be an invasive procedure and alternative ways to deliver the enzyme to the brain are under investigation.
In the case of JR-441, the sulfamidase enzyme is bonded to another molecule, called the transferrin receptor, which can carry the enzyme across the blood-brain barrier. Because of this technology, JR-441 can be injected or infused into the bloodstream intravenously, commonly via a vein in the arm. It is hoped that the new method of enzyme delivery will help treat the neurological symptoms of Sanfilippo with fewer adverse effects.
At the 17th Annual WORLDSymposium, held virtually last year, JCR Pharmaceuticals presented results on their new ERT technology in Sanfilippo types A and B animal models. Their data indicate that intravenous injection of JR-441 in animals increased enzyme levels throughout the brain, with heparan sulfate reduced to near-normal levels.
JCR Pharmaceuticals’ drug JR-141, which uses the same brain delivery technology, is now approved in Japan to treat Hunter Syndrome. Like Sanfilippo, Hunter Syndrome involves the accumulation of material due to an enzyme deficiency and also involves neurological symptoms. Clinical trials of this drug indicated that JR-141 reduced the amount of accumulated material in the fluid surrounding the brains of Hunter Syndrome patients and led to neurocognitive stabilisation or improvement in most patients.
An orphan drug designation helps to ensure that safe and effective medicines for rare diseases can be developed. It gives companies confidence to move forward with clinical trial plans and provides incentives to develop medicines for rare diseases, such as reduced fees, assistance with protocols, and protection against competition for ten years. Importantly, the product development requirements following an orphan designation is still the same as non-orphan medicines: all potential medicines, whether they have an orphan designation or not, are robustly assessed to ensure their quality, safety, and effectiveness before their approval to be on the market.
More information on orphan designation of medicines from the European Medicines Agency (EMA) is available here.
