1111-117 - TRIGLYCERIDE REDUCTION WITH PEGOZAFERMIN IS HIGHLY CORRELATED ACROSS METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS AND SEVERE HYPERTRIGLYERIDEMIA

View session detail

Author Block: Kevin Maki, Teresa Parli, Arun Sanyal, Cynthia Hartsfield, Germaine Agollah, Mildred Gottwald, Maya Margalit, Hank Mansbach, Kemal Balic, Leo Tseng, Deepak Bhatt, Midwest Biomedical Research, Addison, IL, USA, 89bio, San Francisco, CA, USA
Background: There are many similarities between patients with metabolic dysfunction-associated steatohepatitis (MASH) and with severe hypertriglyceridemia (SHTG), including demographics and common metabolic comorbidities. Pegozafermin, an FGF21 analog and a master metabolic regulator, is being studied as a treatment for both disorders.
Methods: We compared the baseline characteristics of patients from the ENLIVEN (MASH) and ENTRIGUE (SHTG) studies. PK/PD profiles in patients treated with pegozafermin QW were also compared.
Results: With the exception of sex, triglyceride (TG) and transaminases, other relevant baseline characteristics between MASH and SHTG patients were generally similar. Pegozafermin PK exposure was comparable between the studied MASH and SHTG populations. Pegozafermin elicited substantial TG reductions in both populations. However, the magnitude of TG lowering effect varied, mainly due to differences in baseline TG levels (Figure 1). Additionally, pegozafermin reduced hepatic fat (as measured by MRI-PDFF) in both populations with similar Emax and EC50 values. These findings support the relevance of the mechanism of action of pegozafermin across patients with SHTG and MASH.
Conclusion: The clinical data confirm pegozafermin's efficacy in related patient populations (SHTG and MASH) and demonstrate robust reductions in triglycerides. As a result, data from the MASH studies may provide supportive evidence of efficacy for treating SHTG.