Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as BIO89-100
Pegozafermin · 7 trials · 5 indications
Fibrosis regression is defined as improvement in fibrosis by ≥1 stage, at Month 24 biopsy relative to baseline biopsy.
Worsening of steatohepatitis is defined as increase in non-alcoholic fatty liver disease (NAFLD) Activity Score (NAS) for ballooning, inflammation, or steatosis
Resolution of steatohepatitis is defined as total absence of ballooning (score=0) and absent or mild inflammation (score 0 to 1). Worsening of fibrosis is defined as progression of fibrosis by ≥1 stage.
Final analysis of the time to first occurrence of disease progression will be measured by a composite of protocol-specified clinical events
Nonalcoholic fatty liver disease activity score (NAS) was the sum of the scores of steatosis, inflammation, and ballooning. NAS score ranged from 0 to 8, with higher scores indicating worse disease severity. Resolution of NASH was defined as the total absence of ballooning (score=0) and absent or mild inflammation (score=0 to 1). NASH clinical research system (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). Worsening of fibrosis was defined as progression of fibrosis greater than or equal to (≥) 1 stage in NASH CRN fibrosis score.
Worsening of NASH was defined as increase in nonalcoholic fatty liver disease activity score (NAS) for ballooning, inflammation, or steatosis. NAS was the sum of the scores of steatosis, inflammation, and ballooning. NAS score ranged from 0 to 8, with higher scores indicating worse disease severity. Fibrosis improvement was defined as ≥1-stage decrease in NASH CRN fibrosis score. NASH CRN fibrosis was staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).
Determine maximum observed serum drug concentration (Cmax)
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were defined as AEs occurring at or after the first dose date and time, through study termination, or existing prior to the time of and worsening after the time of the first dose of investigational product. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were defined as AEs occurring at or after the first dose date and time, through study termination, or existing prior to the time of and worsening after the time of the first dose of investigational product. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
NAS was the sum of the scores of steatosis, inflammation, and ballooning. NAS score ranges from of 0 to 8, with higher scores indicating worse disease severity. Worsening of fibrosis was defined as progression of fibrosis ≥1 stage in NASH Clinical Research Network (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).
| Arm | Type | Description |
|---|---|---|
| Pegozafermin | EXPERIMENTAL | - |
| Placebo | PLACEBO_COMPARATOR | Matched placebo |
| Pegozafermin Regimen 1 | EXPERIMENTAL | - |
| Pegozafermin Regimen 2 | EXPERIMENTAL | - |
| Pegozafermin - 30mg once a week | EXPERIMENTAL | - |
| Pegozafermin - 20mg once a week | EXPERIMENTAL | - |
| Placebo once a week | PLACEBO_COMPARATOR | - |
| BIO89-100 - 15 mg once weekly (QW) | EXPERIMENTAL | - |
| BIO89-100 - 30 mg QW | EXPERIMENTAL | - |
| BIO89-100 - 44 mg once every 2 weeks (Q2W) | EXPERIMENTAL | - |
| Placebo QW | PLACEBO_COMPARATOR | - |
| Placebo Q2W | PLACEBO_COMPARATOR | - |
| Placebo QW (Main study)/ BIO89-100 - 30 mg QW (Extension) | EXPERIMENTAL | - |
| Pegozafermin 9 mg QW | EXPERIMENTAL | Participants received pegozafermin 9 mg QW as an SC injection for 8 weeks in the Main Study cohort. |
| Pegozafermin 18 mg QW | EXPERIMENTAL | Participants received pegozafermin 18 mg QW as an SC injection for 8 weeks in the Main Study cohort. |
| Pegozafermin 27 mg QW | EXPERIMENTAL | Participants received pegozafermin 27 mg QW as an SC injection for 8 weeks in the Main Study cohort or Fibrate Expansion cohort. Main Study and Fibrate Expansion pegozafermin 27 mg QW groups were pooled together due to low sample size in the expansion cohort. |
| Pegozafermin 36 mg Q2W | EXPERIMENTAL | Participants received pegozafermin 36 mg Q2W as an SC injection for 8 weeks in the Main Study cohort. |
| BIO89-100 30 mg, Open Lable, Single Dose | EXPERIMENTAL | - |
| Part 1: Pegozafermin 3 milligrams (mg) weekly (QW) | EXPERIMENTAL | Participants were administered 3 mg of pegozafermin QW, via subcutaneous (SC) injection, starting on Day 1 through Day 85. |
| Part 1: Pegozafermin 9 mg QW | EXPERIMENTAL | Participants were administered 9 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85. |
| Part 1: Pegozafermin 18 mg QW | EXPERIMENTAL | Participants were administered 18 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85. |
| Part 1: Pegozafermin 27 mg QW | EXPERIMENTAL | Participants were administered 27 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85. |
| Part 1: Pegozafermin 18 mg Every 2 Weeks (Q2W) | EXPERIMENTAL | Participants were administered 18 mg of pegozafermin Q2W, via SC injection, starting on Day 1 through Day 85. |
| Part 1: Pegozafermin 36 mg Q2W | EXPERIMENTAL | Participants were administered 36 mg of pegozafermin Q2W, via SC injection, starting on Day 1 through Day 85. |
| Part 1: Placebo QW or Q2W | PLACEBO_COMPARATOR | Participants were administered placebo matching to pegozafermin QW or Q2W, via SC injection, starting on Day 1 through Day 85. |
| Part 2: Pegozafermin 27 mg QW | EXPERIMENTAL | Participants were administered 27 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 134. |
| Name | Type | Description |
|---|---|---|
| Pegozafermin | BIOLOGICAL | Subcutaneous injection |
| Placebo | DRUG | Subcutaneous injection |
| BIO89-100 | DRUG | Subcutaneous injection |
Key Inclusion Criteria: * Males or non-pregnant females aged between 18 and 75 years (inclusive) at time of signing the informed consent form (ICF). * Participants must have type 2 diabetes mellitus diagnosed at least 3 months before screening or at least 2 metabolic risk factors. * Evidence of bot...
Pegozafermin is an investigational monoclonal antibody developed by 89bio, Inc. for metabolic diseases. It is being studied in metabolic dysfunction-associated steatohepatitis (MASH, also called NASH), including MASH with compensated cirrhosis and MASH with fibrosis, and in severe hypertriglyceridemia. It has received Breakthrough Therapy designation from the FDA.
Pegozafermin targets FGF21, fibroblast growth factor 21. By acting on this metabolic hormone pathway, the monoclonal antibody is designed to address the liver and lipid abnormalities studied in MASH and severe hypertriglyceridemia. Its clinical program evaluates effects in patients with these metabolic conditions.
Pegozafermin is developed by 89bio, Inc., which trades under the ticker ETNB. The company is running the Phase 3 clinical program for the drug across MASH with compensated cirrhosis, MASH with fibrosis, and severe hypertriglyceridemia.
Pegozafermin is in Phase 3 clinical development. It is investigational and has not been approved by the FDA. Phase 3 studies are recruiting in MASH with compensated cirrhosis and MASH with fibrosis, and a Phase 3 trial in severe hypertriglyceridemia has been completed.
Pegozafermin is being studied in the recruiting Phase 3 trials NCT06419374 in MASH with compensated cirrhosis and NCT06318169 (ENLIGHTEN-Fibrosis) in MASH with fibrosis. The completed Phase 3 trial NCT05852431 and the completed Phase 2 trial NCT04541186 evaluated severe hypertriglyceridemia. These are randomized, double-blind, placebo-controlled studies.
Pegozafermin is being evaluated for MASH (nonalcoholic steatohepatitis), including patients with compensated cirrhosis and patients with fibrosis. The Phase 3 program is designed to assess its efficacy and safety in these liver disease populations. It remains investigational and is not approved for use.