초록 ▼

○ 목표: 역류성식도염 환자에 대한 제2상 임상시험, 탐색적 추가 임상시험을 완료하여, 제3상 임상시험의 승인 획득 및 다국적 제약사와의 글로벌 임상개발 전략적 제휴 추진
○ 주요내용 및 결과
- 제2상 임상시험: 역류성식도염 환자 150명을 대상으로 YH4808의 안전성 및 유효성 평가를 완료. 시장선도 약물인 Nexium과 동등이상의 유효성 및 안전성 확인됨
- AME 임상시험: [ 14C ]-YH4808 단회경구 투여후 흡수, 대사, 배설에 대한 임상시험 완료 (미국 FDA IND 승인)
- 탐색적 임상시

○ 목표: 역류성식도염 환자에 대한 제2상 임상시험, 탐색적 추가 임상시험을 완료하여, 제3상 임상시험의 승인 획득 및 다국적 제약사와의 글로벌 임상개발 전략적 제휴 추진
○ 주요내용 및 결과
- 제2상 임상시험: 역류성식도염 환자 150명을 대상으로 YH4808의 안전성 및 유효성 평가를 완료. 시장선도 약물인 Nexium과 동등이상의 유효성 및 안전성 확인됨
- AME 임상시험: [ 14C ]-YH4808 단회경구 투여후 흡수, 대사, 배설에 대한 임상시험 완료 (미국 FDA IND 승인)
- 탐색적 임상시험: 식후 PK/PD 임상시험, 약물상호작용 임상시험 2건, 신규제형 임상시험 완료.
- NDA를 위한 비임상독성시험 (발암성시험)을 일정대로 진행하였으며, NSAID에 의한 소장손상에 대한 우수한 보호 효능을 특장점으로서 발굴하고 작용기전을 증명하였음
- 대량생산을 위한 공정개선 (30% 생산비용 절감) 및 동물에서 개선된 BA를 갖는 개선제형을 도출하였음
○ 결론:
- 역류성식도염 환자대상 임상2상시험에서 기존 약물대비 동등이상의 우수한 효능 및 안전성이 확인되었음.
- 향후 역류성식도염에 대한 3상시험 및 국내 NDA, 그리고 추가 적응증에 대한 개발 예정이며, 해외 유수 제약사에 라이센싱아웃을 추진할 계획임

Abstract ▼

I. Aim and Purpose
- Aim: Complete phase 2 study in patients with erosive esophagitis and additional multiple exploratory phase 1 studies and get IND grant for phase 3 study. Pursue global clinical development collaboration with big pharma.
- Purpose: YH4808 is a new drug candidate for acid re

I. Aim and Purpose
- Aim: Complete phase 2 study in patients with erosive esophagitis and additional multiple exploratory phase 1 studies and get IND grant for phase 3 study. Pursue global clinical development collaboration with big pharma.
- Purpose: YH4808 is a new drug candidate for acid related diseases with new mode of action. YH4808 showed excellent inhibitory activity on gastric acid secretion and good tolerance in phase 1 study. Therefore, further PK/PD studies and phase 2 study are worth to perform.
Ⅱ. Scope and Methods
- Phase 2 study: To investigate safety and efficacy of YH4808 in 150 patients with erosive esophagitis and find dose-response relationship.
- AME clinical study: To investigate absorption, metabolism and elimination(AME) after single oral administration of[ 14C ]YH4808 in healthy volunteers (conducted in USA after IND grant from US FDA)
- Exploratory phase 1 studies: To obtain points of differentiation, perform multiple phase 1 studies including postprandial PK/PD, drug-drug interaction study with amoxicillin/clarithromycin and diclofenac, PK/PD study of new formulation
- Nonclinical studies: Toxicity study (carcinogenicity studies) for NDA, hERG assay for metabolites, efficacy studies to identify differentiation point
- CMC research: Production of API and process development, new formulation research to enhance bioavailability
Ⅲ. Results
- Completed phase 2 study in erosive esophagitis patients and YH4808 showed comparable healing rate with current market leading drug, esomeprazole
- IND for AME study was granted from US FDA and study was successfully completed
- Four exploratory phase 1 studies were completed. Food effect was negligible for PK/PD of YH4808 and there were no clinically significant drug-drug interaction with other drugs tested.
- YH4808 showed good efficacy in protecting small intestinal injury induced with NSAID in rats. Also, cytoprotective mechanism of YH4808 was suggested.
- New manufacturing process for API was developed which can reduce 30% of production cost and two related new patents were filed. New formulation with enhanced BA in animal was developed.
Ⅳ. Future plan
- Based on the successful results from this project, phase 3 study will be performed for erosive esophagitis and commercialization in Korea will be pursued.
- Clinical development for additional indication such as NERD and H. pylori eradication will be performed.
- CTD documentation and clinical/nonclinical study results will facilitate partnering with big pharma for global clinical development.