Background: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) has tripled over the past 20 years. However, effective treatments for MASLD and MASH other than diet, exercise, pioglitazone, and tocopherol nicotinate are lacking. This single-arm study investigated the effects of pemafibrate treatment on lipid levels, liver function, diabetes, and weight-related changes in patients with steatotic liver disease.

Methods: Lipid-, liver function-, diabetes-, and weight-related changes before and after pemafibrate administration over 12-14 months were retrospectively analyzed in 38 patients diagnosed with hypertension and concomitant liver dysfunction.

Results: Pemafibrate treatment significantly reduced the levels of alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, triglycerides, and low-density lipoprotein cholesterol. Furthermore, high-density lipoprotein cholesterol levels were slightly increased in men but remained unchanged in women. Nevertheless, hemoglobin A1c levels and body weight remained unchanged in both men and women. After 12-14 months of pemafibrate administration, AST (U/L) significantly decreased from 35 ± 15 to 27 ± 9 (p < 0.01), and ALT (U/L) decreased from 49 ± 29 to 26 ± 16 (p < 0.001). γ-GTP (U/L) was reduced from 73 ± 36 to 43 ± 23 (p < 0.001). Triglycerides (mg/dL) decreased from 263 ± 112 to 145 ± 94 (p < 0.001). HDL-C (mg/dL) increased from 52 ± 13 to 57 ± 15 (p < 0.001), and LDL-C (mg/dL) decreased from 117 ± 2 to 99 ± 25 (p < 0.001), all showing statistically significant differences. In contrast, HbA1c (%) showed no significant change, going from 6.9 ± 0.9 to 6.7 ± 0.7 (p = 0.24), and body weight (kg) remained stable at 74.5 ± 17.8 to 73.6 ± 18.2 (p = 0.84).

Conclusion: These findings suggest that pemafibrate may have potential therapeutic benefits for MASLD and MASH.

In recent years, the so-called "drug loss" issue - in which pharmaceuticals approved in Europe and the United States have not been applied in Japan - has attracted attention. Following the conclusions of the Ministry of Health, Labour and Welfare’s "Study Group on Pharmaceutical Regulations for Strengthening Drug Discovery Capacity and Ensuring Stable Supply," the Ministry has indicated a policy that, from the perspective of ensuring the safety of subjects participating in clinical trials, "in principle, an additional phase 1 study in Japanese is not needed, except in cases where Japanese data are required based on available data regarding safety and tolerability risks." There have been numerous instances in which the pharmacokinetics and safety profiles of Japanese individuals differ significantly from those in Europe and the United States. If Phase III trials are conducted without passing through the safety valve of Phase I trials in Japanese subjects, one cannot help but question whether the safety of Japanese participants can be sufficiently guaranteed. The government has introduced measures to strengthen drug discovery, particularly in Phase I trials. These include revising pharmaceutical regulations in alignment with international harmonization and establishing a globally competitive infrastructure for conducting first-in-human (FIH) trials in Japan. These measures are expected to enhance FIH trial activities and increase their overall number. The necessity of conducting Phase I trials specifically in Japanese populations should be determined scientifically on a case-by-case basis. To facilitate timely drug development, it is essential to make flexible yet scientifically rigorous decisions, ensuring that sufficient data are available to assess risk and safety before initiating Phase III trials in Japan. This paper aims to highlight the necessity of Japanese data in early clinical trials, based on the current discussions surrounding Phase I trial data for Japanese subjects prior to the initiation of multiregional clinical trials.

We conducted an open-label, multicenter clinical trial to evaluate the efficacy and safety of switching from the original drug (NOBELZIN^® Tablets 25 mg/50 mg) to a generic drug (Zinc Acetate Granules 5% Sawai) in patients with Wilson’s disease. The primary endpoint was treatment effectiveness, assessed through alanine aminotransferase (ALT) levels. Secondary endpoints included clinical symptoms such as hepatomegaly, ascites, edema, and neurologic symptoms. Laboratory parameters were also evaluated, which included aspartate aminotransferase (AST), γ- glutamyltransferase (γ-GT), alkaline phosphatase (ALP), serum copper concentration, serum ceruloplasmin level, serum ceruloplasmin-unbound copper (free copper) level, and spot urine copper excretion. The switch from the original to the generic drug did not result in clinically meaningful changes in these endpoints. No significant differences were observed in laboratory tests or vital signs, and adverse events were both mild and within the clinically acceptable range. These findings indicate that the generic drug is as effective and safe as the original drug for individuals with Wilson’s disease.