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PF-05221304 (pf-05221304)
Selective inhibitor of acetyl-CoA carboxylase (ACC1/ACC2) that reduces hepatic lipogenesis and promotes fatty acid oxidation.
PF-05221304, a selective inhibitor of acetyl-CoA carboxylase (ACC1/ACC2) developed by Pfizer, is currently in the early stages of development with no approved indications and 11 ongoing clinical trials. The drug's mechanism of reducing hepatic lipogenesis and promoting fatty acid oxidation offers a unique approach to treating metabolic disorders, distinguishing it from GLP-1 receptor agonists like Semaglutide and Tirzepatide, which have shown superior efficacy in weight management and NASH resolution. A key risk for PF-05221304 is the requirement for a PD-L1 companion diagnostic, which may limit its market accessibility and complicate its development pathway. Despite these challenges, the robust clinical trial program and the unmet need in NASH and related conditions suggest a promising pipeline outlook for this novel therapeutic agent.
At a glance
| Generic name | pf-05221304 |
|---|---|
| Sponsor | Pfizer Inc. |
| Drug class | Acetyl-CoA carboxylase inhibitor |
| Target | Acetyl-CoA carboxylase (ACC1 and ACC2) |
| Therapeutic area | Infectious Disease |
| Phase | discontinued |
Mechanism of action
PF-05221304 works by blocking acetyl-CoA carboxylase, a critical enzyme that catalyzes the first committed step in fatty acid synthesis. In the liver, ACC converts acetyl-CoA to malonyl-CoA, which is essential for building new fat molecules. By inhibiting this enzyme, the drug reduces the production of new hepatic triglycerides, lowering fat accumulation in liver cells. Simultaneously, inhibition of ACC increases the availability of acetyl-CoA for mitochondrial fatty acid oxidation (β-oxidation), promoting the breakdown of existing fat stores. This dual mechanism—reduced fat synthesis plus enhanced fat burning—addresses the core pathophysiology of NASH, where excessive hepatic steatosis drives inflammation and fibrosis. The selectivity for ACC1 and ACC2 isoforms minimizes off-target effects on other metabolic pathways.
Approved indications
Pipeline indications
- Nonalcoholic fatty liver disease (NAFLD) — Phase 2
- Nonalcoholic steatohepatitis (NASH) — Phase 2
- NASH with fibrosis — Phase 2
- NAFLD/NASH (combination therapy with DGAT2i) — Phase 2
Common side effects
Drug interactions
- PF-06865571 (DGAT2 inhibitor)
Competitive intelligence
For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:
- PF-05221304 CI brief — competitive landscape report
- PF-05221304 updates RSS · CI watch RSS
- Pfizer Inc. portfolio CI