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Denifanstat achieved statistically significant results on primary and multiple secondary endpoints in a 52-week clinical trial of 168 NASH patients with stage 2 or 3 fibrosis
- Primary efficacy endpoints:
- NASH resolution without worsening of fibrosis with ≥2-point reduction in NAS (NAFLD Activity Score) in 36% of denifanstat-treated patients vs 13% with placebo (p=0.002)
- ≥2-point reduction in NAS without worsening of fibrosis in 52% of denifanstat-treated patients vs 20% with placebo (p=0.0001)
Denifanstat was generally well-tolerated
Gannex Pharma Co., Ltd., a wholly-owned subsidiary of Ascletis, holds the rights to develop, manufacture and commercialize denifanstat (ASC40) in Greater China under an exclusive license agreement with Sagimet Biosciences Inc.
SHANGHAI, Jan. 23, 2024 /PRNewswire/ -- Gannex Pharma Company Ltd ("Gannex"), a wholly-owned company of Ascletis Pharma Inc. (Ascletis, HKEX:1672), announced that its strategic partner, Sagimet Biosciences Inc. (Sagimet, Nasdaq: SGMT), today reported positive topline results from Sagimet's FASCINATE-2 Phase 2b clinical trial of denifanstat versus placebo in biopsy-confirmed non-alcoholic steatohepatitis (NASH) patients with stage 2 or stage 3 fibrosis (F2/F3) at week 52. In this trial, denifanstat, an oral, selective FASN inhibitor, showed statistically significant improvements relative to placebo on both of the primary endpoints of NASH resolution without worsening of fibrosis with ≥2-point reduction in NAS, and ≥2-point reduction in NAS without worsening of fibrosis. Denifanstat-treated patients also showed statistically significant fibrosis improvement by ≥ 1 stage with no worsening of NASH, and a greater proportion of MRI-derived proton density fat fraction (MRI-PDFF) ≥30% responders relative to placebo.
Gannex holds the rights to develop, manufacture and commercialize denifanstat in Greater China (where it is referred to as ASC40) under an exclusive license agreement with Sagimet. The press release announcing positive topline results from the Phase 2b FASCINATE-2 clinical trial can be found HERE and topline results from the trial can be found below.
Phase 2b FASCINATE-2 Topline Results
Statistical Significance Achieved in Primary Endpoints and Improvements Across Other Endpoints at Week 52 of Denifanstat Treatment
Denifanstat | Placebo | P-value vs | |
Primary Endpoints | |||
NASH resolution without worsening of fibrosis with ≥2-point reduction in NAS | 36 % | 13 % | 0.002 |
≥ 2-point decrease in NAS without worsening of fibrosis | 52 % | 20 % | 0.0001 |
Other Endpoints | |||
Improvement of fibrosis by ≥ 1 stage with no worsening of NASH | 41 % | 18 % | 0.005 |
NASH resolution with no worsening of fibrosis | 38 % | 16 % | 0.002 |
AI digital pathology (qFibrosis)* | -0.3 | 0.1 | 0.002 |
ALT % change from baseline | -30.5 % | -17.2 % | 0.03 |
MRI-PDFF responder rate** | 65 % | 21 % | <0.0001 |
FibroScan AST (FAST) score | -0.3 | -0.1 | <0.0001 |
LDL cholesterol (mg/dL)*** | -19.1 | -9.1 | -- |
Modified intent-to-treat population (mITT) includes all patients with paired biopsies; includes Secondary Endpoints for which analysis has been completed as of the date of this press release.
* Artificial Intelligence (AI) digital pathology assessed by second harmonic generation (SHG, HistoIndex)
** MRI-PDFF responders are patients with ≥30% relative reduction of liver fat at the end of treatment
*** Baseline LDL-C greater than 100 mg/dL; exploratory analysis shown for n=32 and n=27 denifanstat and placebo patients, respectively
Safety and Tolerability
As in prior studies, no treatment-related serious adverse events (SAEs) were observed, and the majority of adverse events (AEs) were mild to moderate in nature (Grades 1 and 2). There were no Grade ≥3 treatment-related AEs. The most common treatment-related AEs by system organ class (observed in ≥5% of patients in the study) were eye disorders (denifanstat 15.2%, placebo 16.1%), gastrointestinal disorders (denifanstat 11.6%, placebo 8.9%), and skin and subcutaneous tissue disorders (denifanstat 22.3%, placebo 7.1%). The incidence of treatment emergent adverse events (TEAEs) leading to treatment discontinuation was 19.6% in the denifanstat group compared to 5.4% in placebo.
About Phase 2b FASCINATE-2 Clinical Trial
The Phase 2b FASCINATE-2 clinical trial was a 52-week randomized, double-blind, placebo-controlled trial that evaluated the safety and histological impact of denifanstat compared to placebo in 168 biopsy-confirmed NASH patients with moderate-to-severe fibrosis (stage F2 or F3) with NAS ≥4.
Patients were randomized 2:1 to receive 50 mg denifanstat or placebo, taken orally once daily. An end-of-trial biopsy was assessed by a central pathologist for histological endpoints. Liver biopsies were also analyzed using AI-based digital pathology.
About Gannex
Founded in 2019, Gannex, a wholly-owned company of Ascletis Pharma Inc., is dedicated to the R&D and commercialization of new drugs in the field of NASH. Gannex has three clinical stage drug candidates against three different targets — FASN, THRβ and FXR — and three combination therapies.
For more information, please visit www.gannexpharma.com
About Ascletis
Ascletis is an innovative R&D driven biotech listed on the Hong Kong Stock Exchange (1672.HK), covering the entire value chain from discovery and development to manufacturing and commercialization. Led by a management team with deep expertise and a proven track record, Ascletis focuses on three therapeutic areas with unmet medical needs from a global perspective: viral diseases, non-alcoholic steatohepatitis (NASH) and oncology. Through excellent execution, Ascletis rapidly advances its drug pipeline with an aim of leading in global competition. To date, Ascletis has multiple drug candidates in its R&D pipeline. The most advanced drug candidates include ASC22 (CHB functional cure), ASC40 (acne), ASC40 (recurrent glioblastoma), ASC40 (NASH), ASC41 (NASH) and ASC61 (advanced solid tumors).
For more information, please visit www.ascletis.com.
