Gannex Announces Poster Presentation of Positive Interim 12-Week Results from Phase II Clinical Trial of ASC41 in Patients with Biopsy-Confirmed MASH at EASL CONGRESS 2024
--Up to 68.2% mean relative reduction in liver fat content from baseline among biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) patients receiving 12-week treatment of ASC41
--Significant and clinically meaningful reductions in l iver fat, alanine aminotransferase ( ALT), aspartate aminotransferase (AST) and lipids as well as excellent safety and tolerability profile demonstrated by ASC41 in MASH patients
The poster presentation titled, "ASC41, a selective THRβ agonist significantly reduces liver fat and ALT in biopsy-confirmed MASH patients after 12-week treatment: an interim analysis of a 52-week serial liver biopsy study", describes significant and clinically meaningful reductions in liver fat, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in biopsy-confirmed MASH patients receiving 12-week treatment of ASC41 tablet, among which the data of ALT and AST notably differentiates ASC41 from other thyroid hormone receptor β (THRβ) agonists currently at clinical or commercial stages. In addition, baseline characteristics from Phase II clinical trials were comparable between ASC41, conducted in
Table 1. Baseline Characteristics
Characteristics |
ASC41 Phase 2 |
Resmetirom Phase 2[1] |
|||
PBO (n=14) |
2 mg (n=13) |
4mg (n=15) |
Placebo (n=41) |
60/80 mg (n=84) |
|
Age, years |
41.2(11.6) |
36.1(11.0) |
34.7(6.5) |
47.3 (11.7) |
51.8 (10.4) |
Male, n(%) |
9(64.3 %) |
12(92.3 %) |
13(86.7 %) |
24 (59 %) |
38 (45 %) |
MRI-proton density fat fraction, % fat fraction (SD) |
18.2%(6.7) |
17.8%(5.4) |
18.9%(7.9) |
19.6% (8.2) |
20.2% (6.8) |
Diabetes, n(%) |
4(28.6 %) |
3(23.1 %) |
3(20.0 %) |
13 (32 %) |
36 (43 %) |
Body-mass index, kg/m² |
28.7(3.1) |
29.7(4.8) |
30.4(5.1) |
33.6 (5.8) |
35.8 (6.2) |
ALT (U/L) |
77.6(56.2) |
65.9(31.2) |
84.8(32.6) |
60.1 (32.2) |
50.0 (29.2) |
AST (U/L) |
47.9(31.6) |
44.2(23.0) |
53.8(18.2) |
38.0 (20.7) |
35.1 (17.7) |
HDL-C (mg/dL) |
44.8(8.7) |
58.4(6.0) |
41.5(6.3) |
45.2 (13.4) |
43.8 (12.5) |
LDL-C (mg/dL) |
116.0(25.4) |
127.5(24.6) |
122.61(25.1) |
116.9 (30.0) |
111.3 (30.4) |
TG (mg/dL) |
156.8(54.0) |
180.4(74.3) |
228.6(126.5) |
161.1 (75.2) |
178.5 (82.4) |
Data are mean (SD) or n (%) unless otherwise stated. |
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[1]. Harrison, S. A., et al.[J] |
In Table 1, "PBO" stands for placebo, "MRI" stands for magnetic resonance imaging, "ALT" stands for alanine aminotransferase, "AST" stands for aspartate aminotransferase, "HDL-C" stands for high-density lipoprotein cholesterol, "LDL-C" stands for low-density lipoprotein cholesterol and "TG" stands for triglycerides. |
ASC41, a once-daily oral tablet, is a liver targeted small molecule and is highly THRβ-selective. The oral tablet formulation was developed utilizing
Table 2. Changes from Baseline (CFB) in LFC, Liver Enzymes and Lipids Biomarkers at Week 12
Parameters |
Placebo |
ASC41 Tablet |
|
2 mg, QD |
4 mg, QD |
||
Mean relative CFB in LFC |
-13.1 % |
-55.0 % |
-68.2 % |
(p = 0.0001) |
(p < 0.0001) |
||
Percentage of patients achieving LFC reduction ≥ 30% |
21.4 % |
92.3 % |
93.3 % |
(p = 0.0002) |
(p < 0.0001) |
||
Percentage of patients achieving LFC reduction ≥ 50% |
21.4 % |
46.2 % |
86.7 % |
(p = 0.24) |
(p = 0.0004) |
||
Percentage of patients achieving ≤5% absolute LFC |
0.0 % |
30.8 % |
66.7 % |
(p = 0.16) |
(p = 0.0017) |
||
Mean relative CFB in ALT |
5.2 % |
-8.5 % |
-32.6 % |
(p = 0.61) |
(p = 0.0051) |
||
Percentage of patients achieving ALT reduction > 17 U/L |
21.4 % |
30.8 % |
73.3 % |
(p = 0.68) |
(p = 0.0052) |
||
Mean relative CFB in AST |
17.3 % |
-3.6 % |
-24.2 % |
(p = 0.67) |
(p = 0.041) |
||
Mean relative CFB in LDL-C |
4.3 % |
-19.4 % |
-23.4 % |
(p = 0.0002) |
(p < 0.0001) |
||
Mean relative CFB in TC |
3.4 % |
-16.8 % |
-20.0 % |
(p < 0.0001) |
(p < 0.0001) |
||
Mean relative CFB in TG |
3.9 % |
-30.6 % |
-42.6 % |
(p = 0.0001) |
(p < 0.0001) |
In Table 2, "LFC" stands for liver fat content, "ALT" stands for alanine aminotransferase, "AST" stands for aspartate aminotransferase, "LDL-C" stands for low-density lipoprotein cholesterol, "TC" stands for total cholesterol and "TG" stands for triglycerides. |
"93.3% of patients receiving treatment with ASC41 experienced at least 30% relative reduction from baseline in liver fat content as assessed by magnetic resonance imaging, proton density fat fraction (MRI-PDFF), which we believe is a strong predictor of fibrosis reduction." said Dr.
ASC41 was generally well tolerated, with adverse events (AEs) being grade 1 in majority across all cohorts in the Phase II clinical trial, including the placebo cohort (see Table 3). No treatment-related serious adverse event (SAE) was reported in any patients receiving ASC41 treatment or placebo. As in prior studies, ASC41 demonstrated excellent gastrointestinal (GI) tolerability.
Table 3. Safety Data
Event, n(%) |
Placebo |
ASC41 Tablet |
|
2 mg, QD |
4 mg, QD |
||
TEAEs |
13(92.9 %) |
13(100 %) |
15(100 %) |
Drug-related TEAEs |
6(42.9 %) |
7(53.9 %) |
7(46.7 %) |
Grade 1 |
6(42.9 %) |
7(53.9 %) |
7(46.7 %) |
Drug-related GI AEs |
2(14.3 %) |
3(23.1 %) |
1(6.7 %) |
Nausea |
0(0.0 %) |
0(0.0 %) |
0(0.0 %) |
Vomiting |
0(0.0 %) |
0(0.0 %) |
0(0.0 %) |
Diarrhea |
1(7.1 %) |
3(23.1 %) |
1(6.7 %) |
Abdominal distension |
1(7.1 %) |
0(0.0 %) |
0(0.0 %) |
Abdominal pain (upper) |
0(0.0 %) |
0(0.0 %) |
0(0.0 %) |
Constipation |
0(0.0 %) |
0(0.0 %) |
0(0.0 %) |
Dyspepsia |
0(0.0 %) |
0(0.0 %) |
0(0.0 %) |
Frequent bowel movements |
0(0.0 %) |
0(0.0 %) |
0(0.0 %) |
In Table 3, "TEAEs" stands for treatment emergent adverse events, "GI" stands for gastrointestinal, "AEs" stands for adverse events and "QD" stands for every day. |
About ASC41
ASC41, a once-daily oral tablet in clinical development for the treatment of MASH, is a liver targeted small molecule which is converted into its active metabolite, ASC41-A, a potent and highly selective THRβ agonist. ASC41 tablet was developed using
About the Phase II Clinical Trial
The randomized, double-blind, placebo-controlled and multi-center Phase II clinical trial (ClinicalTrials.gov: NCT05462353) is being conducted in
About
For more information, please visit www.ascletis.com.
About
Founded in 2019, Gannex is a clinical-stage, wholly-owned company of
For more information, please visit www.gannexpharma.com.
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