Oral Gaucher disease therapy moves ahead with help from EU status
YH35995 is designed to reach the brain and is now in Phase 1 testing
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The European Medicines Agency has given orphan drug designation to YH35995, Yuhan Corporation‘s investigational oral therapy for Gaucher disease, following a similar decision from the U.S. Food and Drug Administration in April.
Orphan drug designation is granted to medicines for rare diseases, defined in the European Union as a condition affecting fewer than 5 in 10,000 people, and in the U.S. as one affecting fewer than 200,000 people. The status is intended to support the development of rare disease therapies by offering incentives to their developers.
EU status may help support YH35995 development
In the EU, orphan drug status comes with more opportunities to interact with regulatory bodies, fee reductions, and access to a centralized authorization procedure, which allows companies to submit a single application for approval across all EU member states. If the treatment is approved, it will also benefit from 10 years of market exclusivity.
The U.S. designation makes Yuhan eligible for user fee waivers, tax credits for clinical trials, and seven years of market exclusivity if the therapy is approved.
YH35995 has demonstrated an ability in preclinical studies to reach the brain — something existing treatments have limited ability to do — and thus has potential for treating both neurological and non-neurological symptoms of Gaucher. Yuhan is now testing the therapy in a Phase 1 trial (NCT06517914) involving healthy adult men.
“We have confirmed the potential in both the U.S. and Europe,” Kim Yeol-hong, MD, PhD, head of research and development at Yuhan, said in a press release. “We will do our utmost to provide meaningful treatment alternatives for patients with rare diseases based on consultations with global regulatory agencies.”
In Gaucher disease, mutations in the GBA1 gene lead to the harmful accumulation of the fatty molecule glucocerebroside (Gb1) in tissues, especially the spleen, liver, and bone marrow. This can cause symptoms such as an enlarged spleen and liver, blood abnormalities, and bone problems.
Gaucher disease type 3 is a form of the condition that is also characterized by neurological symptoms that gradually worsen over time. While existing Gaucher treatments may help ease non-neurological symptoms, they have limited ability to access the brain and address neurological problems.
Therapy designed to reduce harmful Gaucher buildup
YH35995 is an oral therapy belonging to a class of treatments called substrate reduction therapies (SRT). It is designed to lower the production of Gb1 by inhibiting glucosylceramide synthase, an enzyme needed to make it. This is expected to help prevent Gb1 accumulation, potentially easing symptoms and slowing disease progression.
In preclinical studies, YH35995 was reported to significantly reduce Gb1 in both plasma and brain tissue, suggesting it may be able to help with neurological symptoms in Gaucher type 3.
The ongoing first-in-human Phase 1 trial will enroll about 86 healthy adult men, ages 19 to 45, at a medical center in South Korea. In its first part, participants received single, increasing doses of YH35995 or a placebo.
Data presented in May showed that the therapy had a generally favorable safety profile across all tested doses, with dose-dependent reductions in Gb1 observed in plasma. The findings suggested that dosing every four weeks or longer may be appropriate.
Based on the findings, the company is now advancing to the trial’s second part, in which participants will receive multiple oral doses of YH35995 or a placebo every four weeks. There will be three dose groups, in which nine participants will be randomly assigned to receive YH35995 and three will be given a placebo.
The goal is to continue assessing the safety and tolerability of YH35995 and to understand its pharmacokinetics, or how it is processed by the body, and pharmacodynamics, or its effects on the body. The study is expected to be completed by mid-2027.
