Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Pegbelfermin
BMS-986036 · 9 trials · 11 indications
The percentage of participants who achieved a ≥1-stage improvement in fibrosis without worsening of NASH or NASH improvement with no worsening of fibrosis at week 24 in liver biopsy. Improvement in fibrosis is defined by the NASH Clinical Research Network (CRN) Fibrosis Score. Improvement in NASH is defined by a ≥2-stage decrease in the nonalcoholic fatty liver disease activity score (NAS). Worsening of NASH is defined as an increase of the nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) by ≥1 point. Worsening of fibrosis is defined as an increase of fibrosis by ≥1 point as determined by the NASH CRN Fibrosis Score. NASH CRN Fibrosis is staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).
An improvement in fibrosis is defined as a decrease of fibrosis by ≥1-stage in the NASH Clinical Research Network (CRN) Fibrosis Score at week 48 in liver biopsy. Worsening of NASH is defined as an increase of the nonalcoholic fatty liver disease activity score (NAS) by ≥ 1-stage. Worsening of NASH is defined as an increase of the nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) by ≥1 point. Worsening of fibrosis is defined as an increase of fibrosis by ≥1 point as determined by the NASH CRN Fibrosis Score.
The mean change in percent hepatic fat fraction (%) by MRI from baseline to Week 16 was assessed for each arm. A longitudinal repeated measures analysis was used to analyze the change in hepatic fat fraction (%) at Week 16 from baseline in the treated population who have both a baseline and at least one post-baseline measurement.
The number of participants with on-study AEs was reported for each arm.
The number of participants with on-study SAEs was reported for each arm.
The number of participants with on-study injection site reactions was reported for each arm.
The number of participants with on-study AEs leading to discontinuation was reported for each arm.
The number of deaths was reported for each arm.
The number of participants whose worst toxicity grade increased from baseline to grade 3 or 4 (Toxicity Scale: DAIDS Version 1.0) is reported for each arm.
The number of participants with out-of-range vital signs noted during interim or final vital sign assessments was reported for each arm.
The number of participants with out-of-range ECG intervals observed during interim or final electrocardiogram assessments was reported for each arm.
The number of participants with abnormalities observed during interim or final physical examination assessments is reported for each arm.
The mean percent change in bone mineral density from baseline to day 112 reported for each arm.
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Percent Change in Glycosylated Hemoglobin A1c (HbA1c) from Baseline to Week 12 was reported.
Safety
Safety
| Arm | Type | Description |
|---|---|---|
| BMS-986036 Dose Level 1 | EXPERIMENTAL | Administered by subcutaneous injection. |
| BMS-986036 Dose Level 2 | EXPERIMENTAL | Administered by subcutaneous injection. |
| BMS-986036 Dose Level 3 | EXPERIMENTAL | Administered by subcutaneous injection. |
| Placebo | PLACEBO_COMPARATOR | Administered by subcutaneous injection. |
| Treatment Group A: BMS-986036 | EXPERIMENTAL | Administered as specified on specified days |
| Treatment Group B: BMS-986036 | EXPERIMENTAL | Administered as specified on specified days |
| Treatment Group C: Placebo | PLACEBO_COMPARATOR | Administered as specified on specified days |
| Treatment Group D: | EXPERIMENTAL | Administered as specified on specified days |
| Treatment Group E: | PLACEBO_COMPARATOR | Administered as specified on specified days |
| Treatment A: Placebo (Matching with BMS-986036 - Daily) | PLACEBO_COMPARATOR | Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks |
| Arm 2: Treatment B: BMS-986036 (1 mg Daily) | EXPERIMENTAL | BMS-986036 1 mg subcutaneous injection once daily for 12 weeks |
| Treatment C: BMS-986036 (5 mg Daily) | EXPERIMENTAL | BMS-986036 5 mg subcutaneous injection once daily for 12 weeks |
| Treatment D: BMS-986036 (20 mg Daily) | EXPERIMENTAL | BMS-986036 20 mg subcutaneous injection once daily for 12 weeks |
| Treatment E: BMS-986036 (20 mg Weekly) | EXPERIMENTAL | BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks Followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks |
| Group A: Moderate Hepatic Impairment | EXPERIMENTAL | - |
| Group B: Severe Hepatic Impairment | EXPERIMENTAL | - |
| Group C: Normal Hepatic Function | EXPERIMENTAL | - |
| Mild Renal Impairment | EXPERIMENTAL | The renal function will be defined by estimated glomerular filtration rate (eGFR) at Screening. |
| Moderate Renal Impairment | EXPERIMENTAL | The renal function will be defined by estimated glomerular filtration rate (eGFR) at Screening. |
| Severe Renal Impairment | EXPERIMENTAL | The renal function will be defined by estimated glomerular filtration rate (eGFR) at Screening. |
| Normal | OTHER | The renal function will be defined by estimated glomerular filtration rate (eGFR) at Screening. |
| Cohort 1 | EXPERIMENTAL | BMI 18.0 to ≤ 25.0 |
| Cohort 2 | EXPERIMENTAL | BMI \>25.0 to ≤ 30.0 |
| Cohort 3 | EXPERIMENTAL | BMI \>30.0 ≤ 40.0 |
| Module A | EXPERIMENTAL | BMS-986036 Arm |
| Module B | PLACEBO_COMPARATOR | Placebo Arm |
| Name | Type | Description |
|---|---|---|
| BMS-986036 | DRUG | Specified dose on specified days. |
| Placebo | OTHER | Specified dose on specified days. |
| Placebo (Matching with BMS-986036) | BIOLOGICAL | - |
Inclusion Criteria: * Liver biopsy performed within 6 months (26 weeks) prior to the screening period. If historical biopsy is not available, a liver biopsy will be performed during the screening period. Biopsy must be consistent with NASH, with: a) a score of at least 1 for each NAS component (ste...
BMS-986036 is an investigational monoclonal antibody being studied for metabolic liver diseases, including nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), liver fibrosis, and hepatic cirrhosis. It has also been evaluated in type 2 diabetes mellitus and in people with moderate liver impairment. It is not an approved therapy.
BMS-986036 is developed by Bristol-Myers Squibb Company, which trades on the New York Stock Exchange under the ticker BMY. The company sponsored the clinical studies of the asset in NASH, NAFLD, liver fibrosis, and related metabolic and liver impairment populations.
BMS-986036 has reached Phase 2 clinical development. Two completed Phase 2 trials evaluated it in adults with NASH and liver cirrhosis and in adults with NASH and stage 3 liver fibrosis. Additional completed Phase 1 studies assessed drug levels, safety, and tolerability in participants with liver or kidney impairment.
BMS-986036 has been studied in completed trials including NCT03486912, a Phase 2 study in adults with NASH and liver cirrhosis, and NCT03486899, a Phase 2 study in adults with NASH and stage 3 liver fibrosis. Phase 1 trials NCT04634149 and NCT03674476 evaluated the drug in liver impairment and different kidney function levels.
BMS-986036 is not approved and remains an investigational agent in clinical development. Its completed studies include Phase 2 trials in NASH with liver cirrhosis and NASH with stage 3 liver fibrosis, plus Phase 1 trials in participants with liver impairment and varying kidney function. No regulatory approval has been granted for this asset.
Across its completed clinical program, BMS-986036 trials enrolled a total of 219 participants. The largest was a Phase 2 study in NASH and stage 3 liver fibrosis with 197 participants, followed by a Phase 2 NASH and cirrhosis study with 155 participants. The Phase 1 studies were smaller, with 40 and 16 participants.