Ipsen announced that its Phase 3b ELSPIRE trial evaluating Iqirvo (elafibranor) in patients with PBC and ALP 1-1.67x ULN met its primary endpoint of ALP normalization at Week 52.

Ipsen announced that its Phase 3b ELSPIRE trial (N=92; PCD: Jun 2026) evaluating Iqirvo (elafibranor; PPARα/δ agonist) in patients with PBC and ALP 1-1.67x ULN met its primary endpoint of ALP normalization at Week 52.

Key Takeaways:

• Ipsen reported 85% of Iqirvo-treated patients achieved ALP normalization vs 23% on placebo (p<0.0001) and no new safety signals,
• Ipsen plans to present the data at an upcoming medical meeting and submit to regulatory authorities (no specific timelines disclosed in press release), with regulatory decisions regarding ELSPIRE data inclusion in Iqirvo product labels expected in H1 2027
• Iqirvo's ELSPIRE trial compliments Livdelzi's phase 3b IDEAL trial, with differentiation likely dependent on wholistic profiles provided by both PBC 2L therapies

Background:

• The Phase 3b ELSPIRE trial (N=92; PCD: Jun 2026) evaluated elafibranor in PBC patients with inadequate response or intolerance to UDCA treatment (ALP 1–1.67x ULN), with ALP normalization (≤1x ULN) at Week 52 as the primary endpoint.
  • Ipsen reports that 85% of Iqirvo-treated patients achieved the primary endpoint at week 52 vs 23% on placebo
  • Ipsen reports no new safety signals and claims the overall safety profile observed in ELSPIRE is consistent with Iqirvo’s known profile (i.e., ELATIVE and ELATIVE long-term OLE)
  • Additional secondary endpoints were evaluated as part of ELSPIRE, but were not reported in the press release, including:
    • Biochemical: composite response (i.e. ALP < 1xULN with 15% reduction from baseline), “complete” biochemical response (i.e., normalization of TB, ALP, ALT, albumin, and INR), etc.
    • PRO: PBC-40 QoL, PBC NRS, 5D-Itch, PROMIS fatigue, etc.
• Press release highlighted the number of patients with ALP = 1-1.67xULN and positioned ALP normalization as an achievable goal for all PBC patients
  • Ipsen claims ELSPIRE could double Iqirvo’s addressable patient population by expanding to patients with ALP = 1-1.67xULN  
  • Per Q1 2026 earnings, ~20% of current Iqirvo scripts already come from the below 1.67x ULN population despite the absence of trial-level data at the time
  • Management indicated the current Iqirvo label is not restricted to patients above 1.67x ULN, and that ELSPIRE data would "significantly increase" HCP adoption in the below 1.67 segment
• Ipsen confirmed plans to present full ELSPIRE data at an upcoming congress, as well as to submit to regulatory authorities
  • Per company guidance (Q1 2026 EC Q&A), full data from ELSPIRE is expected at AASLD 2026 (November 5–9)
  • Both FDA sNDA filings and EU Type II Variation submission are expected in Q3 2026;
  • A concurrent FDA and EMA submission in Q3 2026 would support a Q1 2027 EMA decisions and Q2 2027 FDA decision, assuming Iqirvo receives standard review for both(base case: standard 10-month FDA review, standard  8-month EMA review)

CI Assessment:

• Identifying new patients, including those with ALP = 1-1.67xULN, could be a strategic focus for the company with OCA-to-PPAR switching now largely complete per Q1 2026 earnings
  • Commercial messaging could precede ESPIRE data regulatory decisions, given Ipsen’s prior claims that a label update is not required to drive prescribing in this population, as the current Iqirvo label is not restricted to patients above 1.67x ULN
  • However, inclusion of ELSPIRE data in Iqirvo’s product label may be required to standardize use, enable payer coverage, and support guideline inclusion

• In June 2026, Gilead reported positive top-line results from its IDEAL trial (N=96; PCD: May 2026) assessing a composite endpoint (i.e. ALP normalization with 15% ALP reduction from baseline) in patients with ALP = 1-1.67xULN.
  • ELSPIRE and IDEAL used different primary endpoint definitions: ELSPIRE used ALP normalization (≤1x ULN) alone, while IDEAL used a composite of ALP ≤1x ULN and ≥15% reduction from baseline, and hence direct comparison cannot be made
  • Full data for both trials is anticipated at AASLD 2026 (November 5–9), placing the two datasets in direct head-to-head comparison at the same congress
  • With Iqirvo and Livdelzi now holding positive data in this segment, differentiation will likely hinge the wholistic efficacy / safety profiles each therapy provides