Table 2.
Change from Baseline to Week 12 in Key Outcomes
| NGM282 1 mg (n = 24) | NGM282 3 mg (n = 19) | |||||||
|---|---|---|---|---|---|---|---|---|
| Baseline | Week 12 | Change From Baseline to Week 12 | P | Baseline | Week 12 | Change From Baseline to Week 12 | P | |
| Histology | ||||||||
| Total NAS score | 5.4 (1.5) | 3.5 (1.4) | −1.9 (1.6) | <0.001 | 5.7 (1.5) | 3.5 (1.3) | −2.2 (1.8) | <0.001 |
| Baseline NAS 3‐6 | 4.6 (1.2) | 3.3 (1.6) | −1.2 (1.5) | 0.005 | 5.0 (1.0) | 3.5 (1.3) | −1.5 (1.3) | 0.001 |
| Baseline NAS 7‐8 | 7.0 (0) | 3.9 (1.1) | −3.1 (1.1) | <0.001 | 7.6 (0.5) | 3.4 (1.3) | −4.2 (1.5) | 0.003 |
| Steatosis | 1.9 (0.9) | 0.9 (0.4) | −1.0 (0.8) | <0.001 | 1.6 (0.8) | 0.5 (0.5) | −1.1 (0.9) | <0.001 |
| Ballooning | 1.4 (0.8) | 1.0 (0.9) | −0.4 (0.9) | 0.030 | 1.8 (0.5) | 1.1 (0.8) | −0.7 (0.9) | 0.003 |
| Inflammation | 2.0 (0.5) | 1.6 (0.5) | −0.4 (0.6) | 0.004 | 2.3 (0.6) | 1.8 (0.5) | −0.5 (0.8) | 0.016 |
| Total fibrosis score | 2.3 (0.8) | 2.2 (0.9) | −0.1 (0.7) | 0.42 | 2.5 (0.8) | 2.0 (0.9) | −0.5 (0.9) | 0.035 |
| Baseline F1 | 1.0 (0) | 1.3 (0.6) | 0.3 (0.6) | 1.0 (0) | 1.3 (0.6) | 0.3 (0.6) | ||
| Baseline F2 | 2.0 (0) | 1.8 (1.0) | −0.2 (1.0) | 2.0 (0) | 1.6 (0.5) | −0.4 (0.5) | ||
| Baseline F3 | 3.0 (0) | 2.9 (0.4) | −0.1 (0.4) | 3.0 (0) | 2.3 (1.0) | −0.7 (1.0) | ||
| Baseline F4 | 4.0 (0) | 3.0 (0) | −1.0 (0) | 4.0 (0) | 3.0 (0) | −1.0 (0) | ||
| Histological response | 12 (50%) | 13 (68%) | ||||||
| NAS ≥2 reduction without fibrosis worsening | 12 (50%) | 12 (63%) | ||||||
| Fibrosis ≥1 reduction without NASH worsening | 6 (25%) | 8 (42%) | ||||||
| NASH resolution without fibrosis worsening | 3 (12%) | 2 (10%) | ||||||
| Imaging | ||||||||
| Liver fat content by MRI‐PDFF (%) | 19.0 (7.2) | 8.0 (5.2) | −11.0 (5.0) | <0.001 | 17.1 (5.6) | 5.9 (4.4) | −11.2 (4.2) | <0.001 |
| cT1 by LiverMultiScan | 918.8 (80.7) | 848.8 (73.8) | −78.2 (53.0) | <0.001 | 891.4 (56.2) | 812.2 (57.6) | −81.6 (57.4) | <0.001 |
| Serum markers of target engagement | ||||||||
| C4 (ng/mL) | 37.7 (27.1) | 6.8 (9.9) | −30.9 (29.3) | <0.001 | 35.0 (24.2) | 1.8 (2.3) | −33.2 (24.4) | <0.001 |
| Total bile acids (μmol/L) | 5.3 (5.6) | 1.7 (1.5) | −3.6 (5.0) | 0.002 | 5.3 (3.1) | 1.4 (1.1) | −4.0 (3.2) | <0.001 |
| Liver enzymes | ||||||||
| ALT (U/L) | 92.2 (53.0) | 28.4 (19.9) | −63.8 (41.9) | <0.001 | 81.7 (39.3) | 28.8 (14.4) | −52.9 (35.8) | <0.001 |
| AST (U/L) | 69.8 (39.0) | 27.4 (17.4) | −42.5 (33.7) | <0.001 | 64.5 (31.9) | 27.2 (9.3) | −37.3 (26.2) | <0.001 |
| Serum fibrosis markers | ||||||||
| Pro‐C3 (ng/mL) | 16.3 (10.1) | 11.8 (5.2) | −4.5 (7.1) | 0.005 | 25.0 (21.6) | 13.9 (8.4) | −11.1 (18.4) | 0.017 |
| ELF score | 9.8 (0.8) | 9.5 (0.8) | −0.3 (0.4) | <0.001 | 10.1 (1.0) | 9.5 (1.0) | −0.6 (0.6) | <0.001 |
| Hyaluronic acid (μg/L) | 61.1 (49.4) | 61.8 (53.0) | 0.7 (27.7) | 0.90 | 91.0 (79.9) | 73.0 (90.7) | −18.1 (50.3) | 0.13 |
| PIIINP (μg/L) | 12.8 (5.9) | 9.7 (3.3) | −3.1 (3.7) | <0.001 | 13.6 (4.7) | 10.3 (3.4) | −3.3 (3.5) | <0.001 |
| TIMP‐1 (μg/L) | 283.0 (64.1) | 243.4 (51.0) | −39.6 (28.2) | <0.001 | 270.5 (68.0) | 227.7 (54.6) | −42.7 (44.6) | <0.001 |
Shown are mean (SD) or n (%). P values by one‐sample t test. Histological response is defined as a 2‐point or greater improvement in NAS without worsening of fibrosis or improvement in fibrosis of one stage or more without worsening of NASH (defined as no increase in NAS for ballooning, inflammation, or steatosis). Resolution of NASH is defined as a score of 0‐1 for inflammation, 0 for ballooning, and any value for steatosis.
Abbreviations: PIIINP, N‐terminal pro‐peptide of collagen III; TIMP‐1, tissue inhibitor of metalloproteinase 1.