Elafibranor has ‘significant, sustained treatment benefit’ in PBC through 78 weeks
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Key takeaways:
- Elafibranor sustained biochemical response and ALP normalization up to week 78 in patients with PBC.
- The PPAR agonist also has potential to reduce pruritis and improve itch-related quality of life.
Elafibranor sustained biochemical response through week 78 in patients with primary biliary cholangitis and has a “potential beneficial effect” on itch-related quality of life, according to late-breaking data presented at EASL Congress.
“There is a major unmet need for a primary biliary cholangitis (PBC) treatment that effectively targets the biochemical indicators of disease progression in PBC, in addition to alleviating quality of life-impacting symptoms,” Christelle Huguet, executive vice president of research and development at Ipsen, told Healio. “Elafibranor, a PPAR agonist and new class of treatment, has the potential to manage disease progression and impact symptoms.”
Efficacy data at week 52 was reported last year at The Liver Meeting in Boston, where Christopher L. Bowlus, MD, chief of gastroenterology and hepatology at UC Davis Health, noted elafibranor achieved biochemical response and improved symptoms of pruritus in patients with PBC.
In the phase 3, randomized, double-blind, placebo-controlled ELATIVE trial, Bowlus and colleagues randomly assigned 161 patients with PBC and inadequate response or intolerance to ursodeoxycholic acid 2:1 to once-daily elafibranor 80 mg (n = 108) or placebo (n = 53) for 52 weeks. Patients remained in the double-blind period for up to 104 weeks or until all patients completed the week-52 visit.
The study’s primary endpoint was biochemical response at week 52 (defined as alkaline phosphatase < 1.67 x upper limit normal) with 15% reduction from baseline and total bilirubin levels at or below the upper limit of normal.
Elafibranor sustains biochemical response
In research reported at EASL Congress, 143 patients completed treatment to week 52 and 43 completed 78 weeks (elafibranor, n = 30; placebo, n = 13).
At week 52, 15% of patients receiving elafibranor achieved ALP normalization vs. no patients on placebo, which was sustained at week 78 (13% vs. 0%). Twenty-five percent of those on elafibranor had not achieved ALP normalization at week 25 but did at week 78, with 75% sustaining normalization from week 52.
“The coprimary endpoint of biochemical response was sustained for 78 weeks of treatment, with 70% of patients on elafibranor meeting the composite endpoint of biochemical response vs. 0% on UDCA alone,” Huguet said.
The least squares (LS) mean change from baseline in total bilirubin improved from week 52 to week 78 among those receiving elafibranor (–0.12 µmol/L vs. –0.82 µmol/L); however, total bilirubin levels worsened in patients receiving placebo, researchers reported. Additionally, improvements were noted in mean change from baseline in gamma-glutamyl transferase and ALP among those who received elafibranor.
According to researchers, other improvements from week 52 to 78 included LS mean change from baseline in alanine aminotransferase (–9.3 U/L to –13.9 U/L) and aspartate aminotransferase (–1.3 U/L to –3 U/L).
‘Potential beneficial effect’ on itch-related quality of life
In additional data presented at EASL, Andreas E. Kremer, MD, PhD, MHBA, head of hepatology at University Hospital Zurich, and colleagues reported the effect of elafibranor on patient-reported pruritus using 5-D itch scale and PBC-40 questionnaire responses.
They conducted a post-hoc analysis of scores to measure change from baseline to week 52 among 66 patients with moderate to severe pruritus (elafibranor, n = 44; placebo, n = 22).
According to results, 58% of patients receiving elafibranor had reduced itching duration vs. 27% receiving placebo. Additionally, 80% of patients assigned to elafibranor improved to occasional or no sleep disturbance vs. 30% assigned to placebo. “Clinically meaningful reductions” were also reported at week 52 in PBC-40 scores among patients receiving elafibranor vs. placebo.
“Elafibranor has a potential beneficial effect of itch-related quality of life, including sleep and functioning as measured using the 5-D itch score and PBC-40 itch domain,” Huguet, said.
This data provides additional evidence that “elafibranor has the potential to address the priority goal of preserving native liver function by slowing disease progression,” Huguet told Healio.
She added: “When treating people with PBC, it’s vital to manage disease progression to prevent or delay liver damage or failure — that is the primary goal of treatment. Evidence from these new data suggest clinicians can be confident in the efficacy of elafibranor, regardless of which biochemical response criteria they may use in their clinical practice. It has a significant and sustained treatment benefit and if approved in the future by regulatory authorities, is an important new treatment option to consider for appropriate patients living with PBC with proven safety and efficacy profile.”
References:
- Ipsen presents long-term elafibranor efficacy and itch-related quality of life data in patients with primary biliary cholangitis. https://www.ipsen.com/press-releases/ipsen-presents-long-term-elafibranor-efficacy-and-itch-related-quality-of-life-data-in-patients-with-primary-biliary-cholangitis/. Published June 5, 2024. Accessed June 6, 2024.
- Kremer AE, et al. Effect of elafibranor on pruritus in primary biliary cholangitis: symptom severity and quality of life measurements from the phase 3 ELATIVE trial. Presented at: EASL Congress; June 5-8,2024; Milan (hybrid meeting).
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Bowlus CL, et al. Efficacy of elafibranor in primary biliary cholangitis: results from the variable double-blind period of ELATIVE, a randomized, placebo-controlled phase 3 trial. Presented at: EASL Congress; June 5-8,2024; Milan (hybrid meeting).
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