Yuhan Corporation Receives Approval for Phase 1 Clinical Trial Plan of 'Rare Disease' Gaucher Disease Treatment

Yuhan Corporation announced on the 1st that it received approval for the clinical trial application (IND) for the Phase 1 clinical trial of YH35995, a treatment for the rare disease Gaucher disease, from the Ministry of Food and Drug Safety on the 28th of last month.

Yuhan Corporation Central Research Institute Exterior [Photo by Yuhan Corporation]

Gaucher disease is a type of lysosomal storage disorder (LSD) caused by a deficiency of a specific enzyme due to genetic mutations. Besides Gaucher disease, LSDs include Fabry disease and Hunter syndrome. Among these, Gaucher disease is a rare disease that manifests systemic symptoms affecting hematologic, organ, and skeletal systems. Clinically, Gaucher disease has three types. Type 1 shows no neurological symptoms but mainly involves accumulation of precursor substances in bones, liver, and spleen, increasing risks of fractures, bleeding tendencies, anemia, and tumor development. Types 2 and 3 present neurological symptoms such as seizures and neurodegeneration acutely or chronically, along with the physical symptoms seen in Type 1. Particularly, Types 2 and 3 Gaucher disease currently have very limited treatment options worldwide, resulting in a high unmet medical need.

The ongoing study is a Phase 1 clinical trial administering YH35995 to humans for the first time. YH35995 will be orally administered to healthy adult males to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics. YH35995 is a glucosylceramide synthase (GCS) inhibitor that reduces the production of glucosylceramide (GL1), classified as a substrate reduction therapy (SRT) small molecule compound developed for oral administration. The compound was licensed from GC Green Cross in 2018. Preclinical trials confirmed excellent efficacy and safety, and notably, it was developed to cross the blood-brain barrier (BBB). Animal studies demonstrated high BBB permeability and a greater and longer suppression of GL1 levels in the brain compared to existing treatments. Therefore, it is expected to provide clinical benefits especially to patients with Type 3 Gaucher disease, who have limited treatment options for neurological symptoms.

Kim Yeolhong, Head of R&D at Yuhan Corporation, stated, "YH35995 has successfully entered the clinical development stage as a result of years of focused efforts on lead compound identification, optimization, and preclinical development at Yuhan’s research institute." He added, "It is significant as Yuhan’s first rare disease treatment under development, and we plan to begin recruiting trial participants soon."