Sagimet Biosciences Presents Positive Phase 2b FASCINATE-2 Clinical Trial Interim Data for Denifanstat for the Treatment of NASH at EASL Congress 2023
23 Junho 2023 - 3:30AM
Sagimet Biosciences Inc., a clinical-stage biopharmaceutical
company developing novel therapeutics targeting dysfunctional
metabolic pathways, today announced an oral presentation of data
from the planned interim analysis of a prespecified subset of
patients at week 26 of the Phase 2b FASCINATE-2 clinical trial of
denifanstat, an investigational fatty acid synthase (FASN)
inhibitor, in nonalcoholic steatohepatitis (NASH) patients with
moderate to advanced fibrosis, stages F2 or F3, as confirmed by
liver biopsy. These results were presented at the European
Association for the Study of the Liver (EASL) Congress being held
in Vienna from June 21-24, 2023, and were previously presented at
The Liver Meeting of the American Association for the Study of
Liver Diseases (AASLD) in November 2022.
Rohit Loomba, M.D., M.H.Sc., Director, NAFLD Research Center,
University of California San Diego, who presented the data,
commented, “The level of response observed in denifanstat-treated
patients at week 26 is consistent with prior clinical results and
encouraging, especially given the favorable tolerability profile.
We are excited by the observed improvement across biomarkers,
including a statistically significant 12.4 mg/dL reduction in LDL
cholesterol and an increase in endogenous FGF21 by 73.1%. FGF21 is
a hormone that regulates important metabolic pathways, in
particular insulin sensitivity, and has been known to decrease
hepatocyte injury while suppressing inflammation and fibrosis. At
week 26, denifanstat-treated patients had an observable change in
circulating blood lipid composition with a decrease in the
di-/triglycerides that are unregulated in NASH and an increase in
cardioprotective polyunsaturated di-/triglycerides. These
denifanstat-driven improvements are consistent with the Phase 2a
FASCINATE-1 findings.”
Improvement Across Biomarkers at Week 26 of Denifanstat
Treatment
|
Denifanstat50 mg (n=30) |
Placebo(n=22) |
P-value vsplacebo |
Relative reduction in liver fat |
- 34.1% |
- 1.5% |
p<0.001 |
≥30% reduction of liver fat (responder rate)* |
67.0% |
18.0% |
p<0.01 |
ALT (U/L) |
- 16.5 |
- 4.0 |
p<0.05 |
Dual liver fat & ALT responder >30% + >17U/L
decrease |
37.0% |
9.0% |
p<0.05 |
PRO-C3** |
- 8.2% |
-1.5% |
p<0.05 |
Enhanced liver fibrosis (ELF) score |
- 0.34 |
- 0.02 |
p<0.05 |
LDL cholesterol (mg/dL) |
- 12.4 |
0.0 |
p<0.05 |
FGF21 |
+ 73.1% |
+ 0.9% |
p<0.01 |
* approximately half of denifanstat responders decreased liver
fat by ≥50%**Roche Diagnostics cobas® assay
As of the cut-off date for this interim analysis population, no
treatment-related serious adverse events were reported, and the
majority of adverse events reported were mild to moderate in nature
(Grades 1 and 2). The incidence of treatment-related treatment
emergent adverse events (TEAEs) was 46.7% (denifanstat) and 27.3%
(placebo), and all were Grade 1 or Grade 2. The incidence of TEAEs
leading to treatment discontinuation were 6.7% (denifanstat) and
4.6% (placebo) Additionally, there was no evidence of drug-induced
liver injury (DILI) and no deaths.
Advanced Lipid Analysis Denifanstat improved
measures of metabolic health by demonstrating a statistically
significant decrease in LDL cholesterol and statistically
significant increase in FGF21, an endogenous hormone primarily
expressed in the liver that is associated with improvements in
metabolic regulation. Using advanced lipid analyses, denifanstat
improved circulating blood lipid composition by reducing the
saturated diglycerides and triglycerides that are elevated in NASH
while increasing polyunsaturated diglycerides and triglycerides,
and reducing lipotoxic ceramides. Changes in these measures are
consistent with improved cardiometabolic health.
“As we continue to advance denifanstat for the treatment of
NASH, we are pleased with the significant improvement across
multiple biomarkers of disease, which are consistent with
FASCINATE-1 results,” said David Happel, Chief Executive Officer of
Sagimet. “We believe the interim Phase 2b data continues to
highlight denifanstat’s differentiated mechanism of action and
reinforces our confidence in its favorable tolerability profile and
broad application potential in NASH. We look forward to presenting
the topline biopsy data in the first quarter of 2024 and are
working towards a subsequent initiation of a pivotal Phase 3
trial.”
About Phase 2b FASCINATE-2 Clinical Trial
The Phase 2b FASCINATE-2 study is a 52-week randomized,
double-blind, placebo-controlled trial evaluating the safety and
histological impact of a 50mg daily oral dose of denifanstat
compared to placebo in 168 biopsy-confirmed NASH patients with
moderate-to-severe fibrosis (stage F2 or F3). The primary efficacy
endpoint is histological (liver biopsy) improvement at week 52 in
nonalcoholic fatty liver disease (NAFLD) activity score (NAS)
without worsening of fibrosis or resolution of steatohepatitis
without worsening of fibrosis. Secondary endpoints include
biomarkers of inflammation, fibrosis and liver injury.
About Sagimet Biosciences
Sagimet is a clinical-stage biopharmaceutical company developing
novel therapeutics targeting dysfunctional metabolic pathways in
diseases, such as NASH, certain cancers and acne. Sagimet compounds
are designed to inhibit FASN, an enzyme involved in the production
of fatty acids normally used for energy storage. In NASH, the
activity of FASN enzyme is upregulated, resulting in excess
accumulation of liver fat, inflammation and fibrosis. Sagimet’s
lead product candidate, denifanstat, an oral, once-daily pill, is
currently being tested in FASCINATE-2, a Phase 2b clinical trial in
NASH with liver biopsy as the primary endpoint. In June 2020,
Sagimet announced positive results from FASCINATE-1, its Phase 2
clinical trial for denifanstat. The results of the Phase 2 clinical
trial were published in
Gastroenterology, the official
journal of the American Gastroenterological Association. For
additional information about Sagimet Biosciences, please visit
www.sagimet.com.
Contact:
Robert UhlManaging Director, ICR
Westwicke858.356.5932robert.uhl@westwicke.com
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