Race Heats Up for Novel Hunter Syndrome Therapies Targeting the Brain

In a significant development for patients with Hunter syndrome, multiple pharmaceutical companies are vying to bring innovative treatments to market that can cross the blood-brain barrier and address cognitive impairment associated with the rare genetic disorder. This competitive landscape is poised to dramatically improve treatment options for the estimated 2,000 patients worldwide affected by this life-threatening condition.

JCR Pharmaceuticals Leads the Pack with Approved Therapy in Japan

JCR Pharmaceuticals has emerged as the frontrunner in the race to develop a brain-penetrating therapy for Hunter syndrome. Their drug, JR-141 (pabinafusp alfa), marketed as Izcargo in Japan, has been approved since 2021. This weekly intravenous infusion consists of iduronate-2-sulfatase fused with an anti-human transferrin receptor antibody, designed to cross the blood-brain barrier.

JCR is currently conducting the STARLIGHT Phase III trial in the United States, building on promising results from earlier Phase I/II trials that demonstrated the drug's ability to limit neurodegeneration. With its head start in the Japanese market, JCR could potentially secure FDA approval within the next two to three years, depending on the outcome of its ongoing trials.

Denali Therapeutics and Regenxbio Advance Competing Candidates

Hot on JCR's heels, Denali Therapeutics is progressing with DNL310 (tividenofusp alfa), a weekly intravenous treatment utilizing their proprietary Enzyme Transport Vehicle technology. DNL310 is currently being evaluated in both Phase I/II and Phase II/III trials. Notably, Denali has announced plans to submit a Biologics License Application (BLA) to the FDA in early 2025.

Denali is also conducting the COMPASS Phase II/III trial, which aims to examine how neuronopathic variations among different Hunter syndrome populations affect treatment outcomes with DNL310.

Meanwhile, Regenxbio is taking a different approach with RGX-121, an AAV9 vector designed to deliver the human iduronate-2-sulfatase gene directly into the central nervous system. Unlike its competitors, RGX-121 is intended as a one-time administration, potentially offering a long-term solution for patients.

In February 2024, Regenxbio reported impressive results from its CAMPSIITE Phase I/II/III trial, demonstrating an 86% reduction in cerebrospinal fluid D2S6, a biomarker highly correlated with Hunter syndrome severity. As of June 2024, Regenxbio was in the process of submitting a BLA for RGX-121.

Emerging Contenders and Future Prospects

While JCR, Denali, and Regenxbio lead the field, other companies are also making strides in Hunter syndrome research. Esteve and Immusoft are in preclinical stages with their respective candidates, EGT-301 and ISP-002. Esteve's approach utilizes AAV-9 gene therapy technology, while Immusoft is exploring the use of engineered B cells to express iduronate 2-sulfatase.

As competition in the Hunter syndrome space intensifies, patients and healthcare providers can look forward to potentially groundbreaking treatments that address both systemic and neurological symptoms of this devastating disorder. With multiple companies pursuing different technological approaches, the next few years promise to be a pivotal period in the development of more effective therapies for Hunter syndrome.