Novel drug helps lessen liver stiffness in high-risk NAFLD

Treatment with the novel, selective peroxisome proliferator-activated receptor α modulator (SPPARMα) pemafibrate appears to produce a significant reduction in liver stiffness but not in liver fat content in patients with high-risk nonalcoholic fatty liver disease (NAFLD), according to the results of a phase II trial.

The trial randomized 118 high-risk NAFLD patients (mean age 53 years, 57.6 percent male) to receive pemafibrate 0.2 mg or placebo orally, twice daily for 72 weeks. The two groups had similar characteristics.

At baseline, 43 patients (36.4 percent) had concomitant type 2 diabetes and 68 (57.6 percent) had dyslipidaemia. The average BMI of the population was approximately 30 kg/m², with insulin resistance suggested by fasting glucose, insulin, and HOMA-IR. Liver fat content was 18.4 percent, while stiffness was 3.1 kPa. Liver stiffness measurement (LSM) was stage 2 or above in more than half of the patients. Serum alanine aminotransferase (ALT) levels were 88.8 U/L.

The primary endpoint of percentage change in magnetic resonance imaging-estimated proton density fat fraction at week 24 was not significantly different between the pemafibrate and placebo groups (−5.3 percent vs −4.2 percent; treatment difference, −1.0 percent; p=0.85).

However, pemafibrate yielded a greater reduction in magnetic resonance elastography-based liver stiffness than placebo at week 48 (treatment difference, −5.7 percent; p=0.036). This difference was maintained through week 72 (treatment difference, −6.2 percent; p=0.024). There were parallel reductions seen in ALT and low-density lipoprotein cholesterol.

Adverse events were comparable in the two treatment groups, and pemafibrate was well tolerated.

The findings suggest that pemafibrate may be a promising therapeutic option for NAFLD and nonalcoholic steatohepatitis, as well as a possible candidate for combination therapy with agents that reduce liver fat content.