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Also known as Pegozafermin
BIO89-100 · 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. * Biopsy-confirme...
BIO89-100 is an investigational small molecule being developed for nonalcoholic steatohepatitis (NASH), a metabolic liver disease. It has been studied in patients with biopsy-confirmed NASH and in patients with compensated cirrhosis due to NASH. It is not approved for any indication and remains in clinical development.
BIO89-100 targets FGF21, a protein in the fibroblast growth factor family. FGF21 is a metabolic regulator, and BIO89-100 is designed as an FGF21-targeted small molecule. This target class places the drug among metabolic therapies being studied for NASH.
BIO89-100 is being developed by 89bio, Inc., which trades on the Nasdaq under the ticker ETNB. The company is the sponsor of the clinical program evaluating the drug in NASH.
BIO89-100 is in Phase 2 development. Its Phase 2 trial in biopsy-confirmed NASH has completed, and a Phase 1 pharmacokinetic study in NASH patients with compensated cirrhosis has also completed. The drug is investigational and has not been approved by the FDA.
BIO89-100 has been evaluated in two completed trials. NCT04929483 was a Phase 2 study of safety, efficacy and tolerability in 222 subjects with biopsy-confirmed NASH. NCT05022693 was a Phase 1 pharmacokinetic study of a liquid formulation in 8 subjects with NASH and compensated cirrhosis.
Across the two completed trials, 230 subjects were enrolled. The Phase 2 NASH study, NCT04929483, enrolled 222 participants, and the Phase 1 pharmacokinetic study, NCT05022693, enrolled 8 participants. Both were randomized, double-blind, placebo-controlled studies in adults aged 21 and older.