Name:
Elafibranor Efficacy and Safety in People with Primary Biliary Cholangitis
Description:
Elafibranor Efficacy and Safety in People with Primary Biliary Cholangitis
Thumbnail URL:
https://cadmoremediastorage.blob.core.windows.net/61f92a9a-99c4-45f4-b7a2-b172aa825778/videoscrubberimages/Scrubber_6.jpg
Duration:
T00H05M05S
Embed URL:
https://stream.cadmore.media/player/61f92a9a-99c4-45f4-b7a2-b172aa825778
Content URL:
https://cadmoreoriginalmedia.blob.core.windows.net/61f92a9a-99c4-45f4-b7a2-b172aa825778/VJBM-2024-0001 - ELATIVE Video v0.3.mp4?sv=2019-02-02&sr=c&sig=Dz6ZTiY6KkhBq4nba5hps%2BYx2vksOBhWgOm11PM2p18%3D&st=2024-10-16T00%3A27%3A37Z&se=2024-10-16T02%3A32%3A37Z&sp=r
Upload Date:
2024-10-07T00:00:00.0000000
Transcript:
Language: EN.
Segment:1 Introduction.
SPEAKER: This animation is a summary of the article entitled "Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis" published in The New England Journal of Medicine.
Segment:2 What is PBC?.
SPEAKER: Primary Biliary Cholangitis, or PBC, is a rare, cholestatic liver disease characterized by a buildup of bile acids leading to chronic inflammation and autoimmune destruction of bile ducts. If untreated, PBC can progress to cirrhosis, liver transplant, and premature death.
SPEAKER: The only licensed first-line therapy in PBC is ursodeoxycholic acid. However, up to 40% of patients receiving ursodeoxycholic acid do not have an adequate response to treatment, or are intolerant to it.
Segment:3 What was the objective of ELATIVE?.
SPEAKER: The objective of ELATIVE was to evaluate the efficacy and safety of elafibranor, a PPAR agonist exerting effects on both PPAR alpha and PPAR delta in patients with PBC who have an inadequate response or intolerance to ursodeoxycholic acid. ELATIVE was a global, double-blind, randomized, placebo-controlled phase III trial conducted in 82 centers. The majority of patients were female and white.
Segment:4 How was the trial conducted?.
SPEAKER: 161 patients were randomized 2 to 1 to receive once daily elafibranor at a dose of 80 milligrams or placebo. Most patients continued their prior ursodeoxycholic acid therapy regimen. Patient demographics and characteristics at baseline were similar between the two groups. Patients received at least 52 weeks of double-blind treatment.
Segment:5 What was the primary endpoint?.
SPEAKER: The primary endpoint in ELATIVE was biochemical response to treatment at week 52, defined as reduction to predefined thresholds in alkaline phosphatase and total bilirubin levels, which are biochemical indicators of cholestasis. Specific alkaline phosphatase and bilirubin level thresholds were key criteria for eligibility.
Segment:6 What did the primary endpoint show?.
SPEAKER: At week 52, a significantly greater proportion of patients receiving elafibranor had a biochemical response compared with those receiving placebo.
Segment:7 What were the secondary endpoints?.
SPEAKER: Key ranked secondary endpoints in the trial included response to treatment according to normalization of alkaline phosphatase at week 52 and change in pruritus intensity from baseline through week 52 and week 24. Based on worst itch numeric rating scale scores in patients with moderate to severe pruritis. At week 52, normalization of alkaline phosphatase occurred only in patients receiving elafibranor with 15% of patients achieving normalization versus 0% receiving placebo.
SPEAKER: In patients with moderate to severe pruritus, there was no statistically significant difference between each group in worst itch numeric rating scale score from baseline to week 52 in least square means.
SPEAKER: Results of the PBC-40 itch and 5-D itch questionnaires suggested possible symptom and quality of life improvements related to the impact of itch in patients with moderate to severe pruritis receiving elafibranor.
Segment:8 What were the overall safety findings?.
SPEAKER: Similar proportions of patients receiving elafibranor or placebo experienced adverse events. No new safety signals were reported in this trial. The safety profile of elafibranor was consistent with that observed in the wider clinical development program.
SPEAKER: Some elevations in creatine phosphokinase and serum creatinine were observed. There were no clinically meaningful changes in renal function. Potential drug-induced liver injury according to predefined thresholds for elevations in aminotransferases and/or bilirubin occurred in one patient receiving elafibranor and two receiving placebo. In all cases, these elevations were reversible and returned, or trended toward baseline following discontinuation of the trial regimen.
Segment:9 Take-home messages.
SPEAKER: Overall, the ELATIVE trial findings demonstrate that elafibranor may provide an effective new treatment for patients with PBC with an inadequate response to ursodeoxycholic acid. Elafibranor received FDA approval in 2024 as second-line treatment in primary biliary cholangitis. The ongoing open-label extension of ELATIVE and a confirmatory phase III trial are assessing the long-term safety of elafibranor and its effects on clinical outcomes.
Segment:10 Disclosures.
SPEAKER: [MUSIC PLAYING]