The FGF21 analog pegozafermin in severe hypertriglyceridemia: a randomized phase 2 trial

Figures

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  Fig. 1. Patient flow diagram. CONSORT flow diagram showing participant disposition and data analysis sets, including reasons for discontinuation. Of the 85 participants treated, 75 (88.2%; n = 59 in pegozafermin and n = 16 in placebo) completed treatment. QW, once-weekly; Q2W, once every 2 weeks.

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  Fig. 2. Effect of pegozafermin on serum TGs. a, Median percent change in TGs from baseline to week 8 (the primary endpoint). b, Proportion of participants who achieved TG responses of <500 mg dl−1, <150 mg dl−1 or a ≥ 50% reduction from baseline to week 8. c–f, TG subgroup analysis among participants (not on background LMT (c), on background LMT (d), without T2DM (e) and with T2DM (f). Data are based on the full analysis set population (defined as all randomized participants who received at least one dose of study treatment, had baseline and at least one postbaseline TG value) and analyzed using the van Elteren test for pooled pegozafermin groups and the Wilcoxon rank-sum test for individual pegozafermin dose groups. n represents independent participants examined at baseline and four postbaseline timepoints for TG-related graphs. All P values are two-sided and based on comparison to the placebo arm. PBO, placebo; PGZ, pegozafermin; QW, once weekly; Q2W, once every two weeks.

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  Fig. 3. Effect of pegozafermin on serum lipids. a–e, LS mean (±s.e.) or median (ApoC3) percent change in non-HDL-C (a), apolipoprotein B (b), apolipoprotein C3 (c), LDL-C (d) and HDL-C (e) from baseline to week 8. Data are based on the full analysis set population (defined as all randomized participants who received at least one dose of study treatment, had baseline and at least one postbaseline TG) and analyzed via MMRM. n represents independent participants examined at baseline and two postbaseline timepoints for lipid-related graphs. All P values are two-sided and based on comparison to the placebo arm. PBO, placebo; PGZ, pegozafermin; QW, once weekly; Q2W, once every two weeks.

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  Fig. 4. Effect of pegozafermin on hepatic steatosis. a, LS mean (±s.e.) percent change from baseline to week 8 in liver fat fraction assessed by MRI-PDFF. b, MRI-PDFF images depicting changes in liver fat fraction from representative participants with elevated baseline liver fat fraction defined as >25%. c, Proportion of participants who achieved liver fat normalization (that is, <5% by MRI-PDFF), ≥30% or ≥50% relative reduction in liver fat after 8 weeks. Data are based on full analysis set population (defined as all randomized participants who received at least one dose of study treatment, had baseline and at least one postbaseline TG) and analyzed using MMRM or the van Elteren test for pooled pegozafermin groups and Wilcoxon rank-sum test for individual pegozafermin dose groups. n represents independent participants examined at baseline and one postbaseline timepoint for liver fat graphs. All individual MRI-PDFF images in b were generated as 384 × 288 mm and color corrected to a common color scale to allow direct comparison across images. MRI-PDFF, magnetic resonance imaging whole liver proton density fat fraction; PBO, placebo; PGZ, pegozafermin, QW, once weekly; Q2W, once every two…

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  Extended Data Fig. 1. Study design. Study design showing the main study and fibrate cohorts as randomized. The 6-week screening period consisted of a 4-week medication/lifestyle stabilization period followed by a 1- to 2-week TG qualification period. EOS, end of study; EOT, end of treatment; MRI-PDFF, magnetic resonance imaging whole liver proton density fat fraction; TG, triglycerides; QW, once weekly; Q2W, once every 2 weeks.

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  Extended Data Fig. 2. Effect of pegozafermin on serum TGs by subgroup. Shown are the 95% CIs for median differences. If the percentage of participants within a subgroup was less than 33% of the overall cohort (n < 6), only descriptive analysis is presented. LMT, lipid modifying therapy; PGZ, pegozafermin.

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  Extended Data Fig. 3. MRI-PDFF imaging. MRI-PDFF images depicting liver fat fraction at baseline and at follow-up (~day 57) in all participants with available data (23 out of 24). Images were generated using a common color-scale for all participants.

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  Extended Data Fig. 4. Waterfall plot. Waterfall plot showing the effect of pegozafermin on liver fat fraction assessed via MRI-PDFF. Data presented for individual participants showing relative change in liver fat from baseline to week 8. Per protocol, the week 8 follow-up MRI-PDFF assessment was to be completed within ±7 days of last dose of study drug, participants noted in asterisks (*) had follow-up MRI-PDFF performed >21 days from date of last dose. The dashed line represents a 30% reduction in liver fat which is commonly used to denote a meaningful change.