Elafibranor Shows Sustained Efficacy for PBC, Improves Pruritus and Fatigue

Kris Kowdley, MD

Credit: Velocity Clinical Research

Findings from interim analyses of the ongoing open-label extension of the phase 3 ELATIVE study highlight the sustained safety and efficacy of elafibranor (Iqirvo) for the treatment of primary biliary cholangitis (PBC), specifically calling attention to the peroxisome proliferator-activated receptor (PPAR) agonist’s impact on pruritus and fatigue for up to 3 years.¹

The data were presented in a pair of late-breaking abstracts at The Liver Meeting 2024 from the American Association for the Study of Liver Diseases (AASLD) in San Diego, California, and report on biomarkers of cholestasis, stabilization of surrogate markers of liver fibrosis, and moderate-to-severe pruritus data for 3 years in patients treated with elafibranor. Additionally, exploratory endpoints for fatigue and sleep were assessed using patient-reported outcomes tools.¹

“Over 3 years, Iqirvo data suggest sustained efficacy and support the safety profile of the medicine. Importantly, when patients tell me they are less impacted by itch and fatigue—that matters to me as a physician,” Kris Kowdley, MD, director at The Liver Institute Northwest and a primary investigator on the ELATIVE study, said in a press release.¹ “Treatment with Iqirvo had an impact on symptoms of pruritus and surrogate markers of fibrosis, which are important findings for people living with PBC.”

The open-label extension included 138 patients who completed the double-blind period of the phase 3 ELATIVE study. The interim analysis presented at AASLD was performed after ≥ 1 year of treatment with elafibranor in the open-label extension, for up to 3 years total.¹

In patients receiving 3 years of continuous treatment with elafibranor across the double-blind period and open-label extension (n = 13), 85% had a biochemical response, defined as alkaline phosphatase (ALP) <1.67 x ULN with ≥ 15% reduction from baseline and total bilirubin ≤ ULN, and 39% achieved ALP normalization at week 156.^1,2

Surrogate markers of liver fibrosis, liver stiffness measurements (n = 23), and enhanced liver fibrosis (ELF) (n = 19) scores suggest stabilization when measured from baseline to week 130. In patients continuously receiving elafibranor for up to 156 weeks, pruritus improvements were sustained for patients with moderate or severe pruritus at baseline (n = 5).^1,2

Additionally, the impact of elafibranor on fatigue and sleep was investigated as an exploratory endpoint in the open-label extension. Changes in fatigue or sleepiness were reviewed from baseline to week 104 looking at the minimal clinically important differences and categorical changes (n = 48). Results showed fatigue and sleep improvements for patients treated with elafibranor were observed at week 104 across 3 patient-reported outcome (PRO) tools.^1,3

In patients with moderate-to-severe fatigue or excessive sleepiness at baseline, clinically meaningful improvements were observed after 104 weeks of treatment with elafibranor in 56% of patients according to the PRO Measurement Information System Fatigue Short Form 7a; 50% of patients according to the fatigue domain of the PBC-40; and 69% of patients according to the Epworth Sleepiness Scale.^1,3

“Fatigue is a symptom often reported by people living with PBC and is also very challenging to manage,” Mark Swain, MD, a professor in the department of medicine at Cumming School of Medicine at the University of Calgary, said in a press release.¹ “Patients treated with Iqirvo reported improvement in fatigue and sleep, across several patient-reported outcome measures.”

References

1. ^{Ipsen. Iqirvo® (elafibranor) data shows efficacy and safety for up to 3 years in patients with PBC with improvements in fatigue and pruritus. November 15, 2024. Accessed November 19, 2024. https://www.ipsen.com/us/press-releases/iqirvo-elafibranor-data-shows-efficacy-and-safety-for-up-to-3-years-in-patients-with-pbc-with-improvements-in-fatigue-and-pruritus-2982128/}
2. ^{Kowdley K, Bowlus CL, Levy C, et al. 5041 - Long-term efficacy and safety of elafibranor in primary biliary cholangitis: Interim results from the open-label extension of the ELATIVE® trial up to 3 years. Paper presented at: AASLD’s The Liver Meeting 2024. San Diego, California. November 15-19, 2024.}
3. ^{Swain M, Jones D, Levy C, et al. 5042 - Impact of elafibranor on fatigue in patients with primary biliary cholangitis: Interim results from the long-term open-label extension of the ELATIVE® trial. Paper presented at: AASLD’s The Liver Meeting 2024. San Diego, California. November 15-19, 2024.}