Elafibranor held its biochemical gains in PBC across three years

Elafibranor, an oral drug for the autoimmune liver disease primary biliary cholangitis (PBC), kept improving patients' liver blood tests through two years of blinded treatment and up to three and a half years of open-label follow-up, according to extended results from the phase 3 ELATIVE trial [s1]. The finding matters because elafibranor won accelerated approval on a single year of data, and the open question was whether its effect would hold — or fade — with time. The longer read is reassuring on durability, but it does not change the central caveat: the benefit is measured on a blood marker, not yet on how long patients live or avoid a transplant [s1].

PBC is a chronic disease in which the immune system attacks the small bile ducts inside the liver, causing bile acids to back up and, over years, scarring that can progress to cirrhosis. It mostly affects women, and its two most disabling symptoms are relentless fatigue and itch. The standard first-line treatment is ursodeoxycholic acid, but a substantial minority of patients respond inadequately, and those patients face a higher risk of progression. Elafibranor is a once-daily activator of the PPAR-α/δ receptors, a different mechanism aimed at that inadequate-responder group.

What the trial did

ELATIVE was a randomised, double-blind, placebo-controlled trial funded by Ipsen, which markets the drug [s1][s2]. It enrolled 161 patients and assigned them 2:1 to elafibranor 80 mg or placebo [s1]. The double-blind period ran in two parts: a 52-week common period, then a variable period that kept patients on their assigned treatment for up to 104 weeks in total, after which they could enter an open-label extension and all receive elafibranor [s1]. That design is what allows a two-year look at the blinded comparison and a three-year look at those who stayed on the drug.

The endpoint throughout is biochemical: a composite response defined by liver blood tests, and the stricter goal of normalising alkaline phosphatase (ALP), the enzyme that tracks bile-duct injury in PBC [s1]. Sustained normal ALP is associated in observational data with better long-term outcomes, which is the reasoning behind using it as a surrogate — but an association is not the same as a trial proving the drug extends survival, and ELATIVE was not designed or sized to show that [s1].

What it found

At week 104 of the blinded period, 64.3% of elafibranor-treated patients (18 of 28 still in the comparison) achieved a biochemical response and 10.7% (3 of 28) normalised their ALP, versus none of the placebo group on either measure [s1]. Among patients with moderate-to-severe symptoms at the start, the drug group reported larger improvements than placebo on standardised scales for fatigue (a mean change of −6.3 versus −0.4) and for worst itch (−4.1 versus 0.3), though the trial describes these symptom changes as numerical rather than confirmatory [s1].

The open-label data speak to durability. Of 138 patients who entered the extension, the 93 who had been on elafibranor continuously maintained a biochemical response in 58.8% (47 of 80) at week 104 and 65.0% (13 of 20) at week 156, with ALP normalisation rising from 15.0% to 25.0% over the same window [s1]. Patients who crossed over from placebo also responded: 51.2% (21 of 41) reached a biochemical response and 22.0% (9 of 41) normalised ALP after 52 weeks on the drug [s1]. Across a maximum exposure of 3.5 years, the trial reported no unexpected safety findings [s1].

How to read it

The honest summary is that elafibranor does what a second-line PBC drug is approved to do — durably move the biochemical markers that predict worse disease — and does it in patients who need an alternative to first-line therapy [s1]. The improvements in fatigue and itch, if they hold up in larger symptom-focused studies, would matter to patients as much as any laboratory value.

The limits are equally real. The comparison rests on a surrogate endpoint, and the blinded groups shrank as patients moved into open-label treatment, so the two-year percentages come from modest numbers [s1]. The trial is sponsored by the drug's maker, and an open-label extension in which everyone knows they are taking the active drug cannot, by design, control for the placebo effect on symptoms [s1]. What it cannot yet tell a reader is whether starting elafibranor changes the odds of avoiding cirrhosis, transplant or death — the outcomes that ultimately justify a lifelong medicine.

What to watch

The field's next question is confirmatory outcome data: whether the biochemical gains translate into fewer hard liver events over longer follow-up, and how elafibranor compares with the other second-line option, the related drug seladelpar. Real-world registries and any event-driven trial will decide where it sits in practice.

This article describes research and regulatory context and is not medical advice. Treatment of PBC is a decision for treating clinicians.

Sources

• Elafibranor in primary biliary cholangitis: two-year outcomes and long-term data from ELATIVE — Journal of Hepatology, 27 August 2026
• ELATIVE trial record (NCT04526665) — ClinicalTrials.gov