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Table 2 Overview of published Phase II/III clinical trials with pemafibrate

From: The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential

Citation

Patients

Treatment daily dose (mg) and duration

Key findings

Ishibashi [132]

Phase II

N = 224 with high TG + low HDL-Ca

Pemafibrate 0.05, 0.1, 0.2, 0.4

Fenofibrate 100

Placebo

12 weeks

LS mean [SE] percent changes from baseline to 12 weeks (pemafibrate 0.4 vs. fenofibrate)

Decrease in TG: 42.7 [6.7]% vs. 29.7 [6.7]%

Increase in HDL-C: 21.0 [2.8]% vs. 14.3 [2.8]%

LS mean [SD] percent decrease (pemafibrate 0.4 vs. fenofibrate)

VLDL-C: 48.4 [27.5]% vs. 25.8 [29.7]%**

Remnant-C: 50.1 [31.8]% vs. 31.8 [35.0]%

Apo C-III: 33.4 [19.2]% vs. 27.2 [18.9]%

Increase in FGF21 (pemafibrate vs. fenofibrate)***

The incidence of adverse events with pemafibrate, fenofibrate or placebo was similar

Conclusion: In dyslipidemic patients with high TG and low HDL–C, pemafibrate improved TG, HDL-C, and other lipid parameters without increasing adverse events, compared to placebo and fenofibrate

Ishibashi [134]

Phase III

N = 225 with high TG and low HDL-Cb

Pemafibrate 0.2, 0.4 vs. Fenofibrate 106.6

24 weeks

LS mean [SE] reduction from baseline to 24 weeks in TG: 46.2 [2.0]% with pemafibrate 0.2 and 45.9 [1.9]% with 0.4 vs. 39.7 [1.9]% with fenofibrate*

At 24 weeks, significant ↓ALT** and GGT** with pemafibrate compared with fenofibrate

Conclusion: Pemafibrate was superior to fenofibrate in terms of serum TG-lowering effect and hepatic and renal safety

Arai [133]

Phase III

N = 526 with high TG and low HDL-Ca

Pemafibrate 0.1, 0.2, 0.4

Fenofibrate 100, 200 vs. placebo

12 weeks

Non-inferior LS mean [SE] decrease in TG vs. fenofibrate 200: 46.7 [1.6]% with pemafibrate 0.2 and 51.8 [2.0]% with 0.4 vs. 51.5 [1.6]%

No dose-dependent increase in adverse events with pemafibrate

The incidence of adverse events for all pemafibrate doses was similar to that for placebo and fenofibrate 100 and significantly lower than fenofibrate 200 mg*

Conclusion: The favorable safety profile of pemafibrate, with fewer adverse effects on kidney/liver-related tests and fewer adverse events over fenofibrate 200 mg/day, may justify the use of this novel and potent treatment option for reducing TG in a broader range of patients

Arai [135]

Phase III

2 trials, dyslipidemia on statin therapy

Trial Ac: N = 188

Trial Bd: N = 423

Trial A

Pemafibrate 0.1, 0.2, 0.4 vs. placebo

12 weeks

Trial B

Pemafibrate: 0.2, 0.2/0.4g vs. placebo

24 weeks

Trial A

 LS mean [SE] decrease in TG at 12 weeks: 53.4 [3.8]% with pemafibrate 0.2, 52.0 [3.9]% with 0.4 vs. 6.9 [4.0]% with placebo, p < 0.001

Trial B

 LS mean [SE] decrease in TG at 24 weeks: 46.8 [2.6]% with pemafibrate 0.2, 50.8 [2.5]% with 0.2/0.4 vs. 0.8 [3.0]% with placebo, p < 0.001

 34% of patients were titrated to the higher dose

In both trials, pemafibrate ameliorated the atherogenic lipoprotein profiles, i.e. ↓small LDL, ↑ larger LDL and ↓larger HDL, ↑ small HDL

Conclusion: These results strongly support the favourable benefit-to-risk ratio of pemafibrate add-on therapy in combination with statin treatment

Araki [136]

Phase III

N = 166, T2DM with high TGe

Pemafibrate 0.2, 0.4 vs. placebo

24 weeks

LS mean reductions with pemafibrate vs. placebo

 TG: 44.3% with 0.2, 45.1% with 0.4 vs. 10.8%, p < 0.001

 Non-HDL-C 6.3% and 12.5%, remnant-C 45.7% and 49.2%, apo B100 9.1% with 0.2 mg, apo B48 43.7% and 50.6%, and apo C-III 32.5% and 34.0%, all p < 0.001

 HOMA-insulin resistance score with 0.2 mg, p < 0.05

 Both pemafibrate doses significantly ↑ FGF21, p < 0.001

Conclusion: Pemafibrate significantly ameliorated lipid abnormalities and was well tolerated in patients with T2DM with hypertriglyceridemia

Yamashita [137]

N = 33 with atherogenic dyslipidemiaf

Crossover study, pemafibrate 0.4 or placebo

Each period was 4 weeks

Significant (p < 0.001) mean percent LS [SE] changes with pemafibrate vs. placebo

 Decreases in TG (39.8 [19.4]% vs. increase of 22.5 [36.0]%), non-HDL-C (12.0 [19.9]% vs. increase of 3.5 [12.6]), remnant-C (50.6 [24.5]%), vs. increase of 17.5 [35.6]%, and apo C-III (31.3 [20.1]% vs. increase of 11.6 [28.3]%)

 Increases in HDL-C (16.1 [15.0]% vs. decrease 1.4 [10.6]%), apo A–I (8.3 [9.1]% vs. 1.3 [9.8]%) and apo A-II (38.2 [17.4]% vs. 5.5 [12.6]%)

 Pemafibrate significantly increased FGF21 (p < 0.001), and decreased hsCRP and serum amyloid A (p < 0.01) vs. baseline

 Pemafibrate improved postprandial hyperlipidemia

 Pemafibrate improved HDL quality (macrophage cholesterol efflux capacity) and increased preβ1 HDL and HDL3

Conclusion: Pemafibrate enhances reverse cholesterol transport and may retard the progression and even promote the regression of atherosclerosis by comprehensively ameliorating the atherogenic lipid profile

  1. ALT, alanine aminotransferase; FGF21, fibroblast growth factor 21; GGT, gamma glutamyl transferase; HDL-C, high-density lipoprotein cholesterol; hsCRP, high-sensitivity C-reactive protein; LS, least squares; SD, standard deviation; SE, standard error; VLDL-C, very low-density lipoprotein cholesterol; TG, triglycerides
  2. * p < 0.05, ** p < 0.01, *** p < 0.001 vs. fenofibrate
  3. Dyslipidemia defined as:
  4. aTG ≥ 2.23 mmol/L and HDL-C < 1.3 mmol/L in men < 1.4 mmol/L in women
  5. bTG ≥ 1.7 mmol/L and < 5.7 mmol/L and HDL-C < 1.3 mmol/L in men and < 1.4 mmol/L in women
  6. cTG ≥ 2.23 mmol/L and non-HDL-C ≥ 3.9 mmol/L
  7. dTG ≥ 2.23 mmol/L
  8. eTG ≥ 1.7 mmol/L
  9. fTG ≥ 1.7 mmol/L and < 4.5 mmol/L and HDL-C < 1.3 mmol/L in men and < 1.4 mmoL/L in women
  10. gPemafibrate was up titrated from 0.2 mg/day to 0.4 mg/day after week 12 if fasting TG were ≥ 1.7 mmol/L at week 8
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Cardiovascular Diabetology

ISSN: 1475-2840