Gannex's Strategic Partner Sagimet Biosciences Announces Positive Topline Results from Phase 2b FASCINATE-2 Clinical Trial of Denifanstat in Biopsy-Confirmed F2/F3 NASH
- Statistically significant improvements in NASH resolution and fibrosis reduction
- No serious adverse events observed
- Denifanstat was generally well-tolerated
- None.
Insights
The statistical significance of denifanstat's efficacy in NASH patients with stage 2 or 3 fibrosis suggests a robust clinical profile that could translate into a substantial market opportunity. The data indicating a 36% resolution rate in NASH without fibrosis worsening and a 52% reduction in NAS without fibrosis worsening are particularly noteworthy, as current treatments are limited. The improvement in MRI-PDFF responder rates also underscores the potential for denifanstat to become a preferred treatment option, given the importance of non-invasive biomarkers in managing liver diseases.
Furthermore, the safety profile, characterized by no serious adverse events and a predominance of mild to moderate side effects, enhances the drug's marketability. However, the 19.6% discontinuation rate due to adverse events in the denifanstat group, compared to 5.4% in the placebo group, may raise concerns about tolerability, warranting further investigation.
From an industry perspective, the success of denifanstat in the FASCINATE-2 trial could lead to a shift in the competitive landscape of the NASH treatment market. NASH is a condition with a significant unmet medical need and a growing patient population, which makes effective treatments highly sought after. The licensing agreement between Gannex and Sagimet for the Greater China market suggests a strategic move to capitalize on this opportunity in a key emerging market.
The potential approval and subsequent commercialization of denifanstat in this region could have a positive impact on Ascletis Pharma's revenue streams and market position. Investors may view these clinical results as a strong indicator of future financial performance, especially considering the high prevalence of NASH in the global population and the limited number of approved treatments.
The clinical success of denifanstat could have a material impact on the stock performance of both Sagimet Biosciences and Ascletis Pharma. Positive clinical trial results often lead to an uptick in stock prices due to increased investor confidence in the drug's market potential. Given the size of the NASH market and the efficacy and safety profile of denifanstat, the drug's progress through the regulatory pathway could significantly influence both companies' valuations.
Investors will likely monitor upcoming regulatory milestones and potential market penetration rates closely. The exclusive licensing agreement for Greater China could also play a critical role in revenue forecasts for Ascletis, as successful commercialization in this region may set a precedent for future licensing deals in other territories.
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 vs13% with placebo (p=0.002) - ≥2-point reduction in NAS without worsening of fibrosis in
52% of denifanstat-treated patients vs20% 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
Gannex holds the rights to develop, manufacture and commercialize denifanstat in
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 ≥
*** 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 ≥
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.
View original content:SOURCE Ascletis Pharma Inc.
FAQ
What are the primary efficacy endpoints achieved in the FASCINATE-2 trial for denifanstat (SGMT)?
What rights does Gannex Pharma Co., Ltd. hold for denifanstat (SGMT)?
What were the safety and tolerability findings for denifanstat (SGMT) in the FASCINATE-2 trial?
