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IQIRVO elafibranor 80 mg tablets
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IQIRVO elafibranor 80 mg tablets
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The IQIRVO Effect

The only pivotal study for PBC in which

40% of patients had baseline ALP >3 x ULN1

The ELATIVE® trial was a double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of IQIRVO in patients with PBC and inadequate response or intolerance to UDCA.2

  • Placebo + UDCA referred to as “UDCA alone”
  • 95% (153/161) of patients on IQIRVO in the ELATIVE trial received concurrent UDCA therapy2
  • ULN for ALP was defined as 104 U/L for women and 129 U/L for men2
ELATIVE trial design schematic desktop ELATIVE trial design schematic mobile

Baseline characteristics1

IQIRVO + UDCA
(n=108)

UDCA alone
(n=53) 

OLE crossovera
(n=45) 

Sex, female %

94

98

98

Age <65 years %

76.9

81.1

 

Years since 
diagnosis (±SD)

7.9 
(5.9)

8.3 
(6.8)

9.5 
(6.6)

Mean (±SD) 
baseline ALP U/L

321.3 (121.9)

323.1 (198.6)

335.8 (187.9)

ALP >3 x ULN %

39.8

37.7

42.2

Mean (±SD) baseline total bilirubin mg/dL

0.57 
(0.30)

0.55 
(0.29)

0.64 
(0.53)

Mean PBC WI-NRS score

3.3

3.2

 

Mean liver stiffness kPa

9.9

10.7

 

Liver stiffness 
>10 kPa and/or 
bridging fibrosis or 
cirrhosis on histology 
%

34

38

31

~41% of patients had moderate-to-severe pruritus3

 

~35% started the trial with advanced disease1,3,b

First second-line PBC treatment in which 13x more patients achieved biochemical response vs UDCA alone2

Biochemical response at 52 weeks2:

Blue IQIRVO checkmark icon

ALP <1.67 x ULN

Blue IQIRVO checkmark icon

ALP decrease ≥15% from baseline

Blue IQIRVO checkmark icon

Total bilirubin ≤ ULN

Biochemical response at week 522,c,d

51% biochemical response achieved with IQIRVO vs 4% with UDCA 51% biochemical response achieved with IQIRVO vs 4% with UDCA Mean decrease from 321 U/L at baseline to 175 U/L or lower (1.67 x ULN)—a mean reduction of 146 U/L Mean decrease from 321 U/L at baseline to 175 U/L or lower (1.67 x ULN)—a mean reduction of 146 U/L

cALP values are based on a weighted average of the ULN; 105 U/L is the weighted ULN based on a ULN of 129 U/L for men and 104 U/L for women.2

dSix patients in the IQIRVO group took IQIRVO alone, while 2 patients in the UDCA group took placebo alone.2

    Patient profile example: Inadequate response to first-line treatment

    Helen, age 42

    Disease history

    • 24 months since diagnosis
    • Treated with UDCA (900 mg daily) for 24 months
    • Current ALP 218 U/L (2.1 x ULN) vs 353 U/L (3.4 x ULN) at diagnosis4
    • 220 U/L ALP at 6-month marker vs 240 U/L at 12 months after starting therapy
    • Current bilirubin 0.56 mg/dL (normal) vs 0.56 mg/dL (normal) at diagnosis5

    Risk factors for progression

    • Inadequate response to first-line treatment6
    • Age <45 at diagnosis6,7

    ALP levels with first-line treatment

    Patient profile line graph showing ALP decrease over 6 months Patient profile line graph showing ALP decrease over 6 months

    With IQIRVO, 15% of patients were able to achieve ALP normalization of 105 U/L or lower. Lowering ALP is a key treatment goal in managing PBC2,8

    Hear key opinion leaders Dr. Kowdley, Dr. Kumar, and Dr. Flamm discuss biochemical response and normalizing ALP with IQIRVO

    Hear key opinion leaders
    Dr. Kowdley, Dr. Kumar, and Dr.
    Flamm discuss biochemical
    response and normalizing ALP
    with IQIRVO

    Watch the video

    71% of patients in a subgroup analysis saw biochemical response1

    In patients with ALP ≤3 x ULN at baseline 
    Biochemical response at week 521,c

    Bar chart showing percentage of patients taking IQIRVO in a subgroup analysis that saw biochemical response Bar chart showing percentage of patients taking IQIRVO in a subgroup analysis that saw biochemical response

    ALP1

    IQIRVO 
    + UDCA

    UDCA 
    alone

    ≤2 x ULN

    87%

    13%

    >2 – ≤2.5 x ULN

    80%

    0%

    >2.5 – ≤3 x ULN

    52%

    0%

    In patients with ALP >3 x ULN at baseline
    21% (n=9/43) of patients saw biochemical response1

    Risk difference: 21% (95% CI: 2% to 35%)

    In patients with ALP >3 x ULN at baseline
    21% (n=9/43) of patients saw biochemical response1

    Risk difference: 21% (95% CI: 2% to 35%)

    cALP values are based on a weighted average of the ULN; 105 U/L is the weighted ULN based on a ULN of 129 U/L for men and 104 U/L for women.2

      Patient profile example: Unresponsive to current second-line treatment

      Marie, age 57

      Disease history

      • 5 years since diagnosis
      • Second-line treatment added 6 months ago, in combination with UDCA (prescribed at diagnosis)
        • 5 years (UDCA), 1.5 years (UDCA + obeticholic acid)
      • Recently reported symptoms of increased pruritus
      • Current ALP of 239 U/L (2.3 x ULN) vs 187 U/L (1.8 x ULN) at diagnosis4

      IQIRVO could help patients like Marie achieve biochemical response with an established safety profile2

      Review safety and tolerability findings for IQIRVO.

      Rapid ALP reduction as early as 4 weeks, sustained over 3 years1

      ALP reduction from baseline1

      Line chart showing ALP reduction from baseline Line chart showing ALP reduction from baseline through 52 weeks Line chart showing ALP reduction from baseline from 52 weeks through 156 weeks

      37% reduction in ALP
      as early as 4 weeks with IQIRVO1

      37% reduction in ALP
      as early as 4 weeks with IQIRVO1

      ALP reduction across subgroups Powerful ALP reduction, regardless of starting point1

      Mean change from baseline to week 52 in ALP, 
      stratified by baseline ALP levels1

      Bar chart showing mean change from baseline to week 52 in ALP levels, stratified by baseline ALP levels<sup>5</sup> Bar chart showing mean change from baseline to week 52 in ALP levels, stratified by baseline ALP levels<sup>5</sup>

      Data are presented descriptively.

      A 22x greater reduction in ALP with IQIRVO vs UDCA alone3

      LS mean change from baseline: IQIRVO -117 U/L, UDCA -5.3 U/L3

      Normalization at 52 weeks in a pivotal study2
      Target an ALP of 105 U/L or lower—only with IQIRVO2,c

      ALP normalization at week 522

      Bar chart showing ALP normalization achieved with IQIRVO vs UDCA alone Graphic illustrating mean ALP decrease from 321 U/L at baseline to 105 U/L or lower Bar chart showing ALP normalization achieved with IQIRVO vs UDCA alone

      (n=108)(n=53)

      Graphic illustrating mean ALP decrease from 321 U/L at baseline to 105 U/L or lower

      cALP values are based on a weighted average of the ULN; 105 U/L is the weighted ULN based on a ULN of 129 U/L for men and 104 U/L for women.2

      Data on reduction of pruritus with IQIRVO3

      IQIRVO was studied in patients with moderate-to-severe pruritus, defined as a PBC WI-NRS score ≥4. The change in pruritus from baseline through weeks 24 and 52 were secondary endpoints of the study3

      Results with IQIRVO presented below were not statistically significant and, therefore, these results are descriptive only.3

      A trend toward improving pruritus was observed with IQIRVO, as measured by WI-NRS (LS mean change from baseline -1.93 vs -1.15 with UDCA alone; 95% CI: -2.0 to 0.4).3

      Pruritus impact vs UDCA alone was measured by PBC-40 and 5-D itch scales3,d

      PBC-40 itch domain at week 523

      IQIRVO PBC-40 itch domain bar graph IQIRVO PBC-40 itch domain bar graph

      The PBC-40 is a patient-derived measure validated for PBC, covering 6 domains: fatigue, pruritus, cognitive, emotional, social, and other symptoms.9

      A 0.5-point change per question in the itch domain was a threshold for response, with ≥1.5 change being clinically meaningful.9,10

      5-D itch score at week 523

      IQIRVO 5-D itch score bar graph IQIRVO 5-D itch score bar graph

      The 5-D itch scale is a patient-reported measure of the degree, duration, direction, disability, and distribution of pruritus.11

      dSix patients in the IQIRVO group took IQIRVO alone, while 2 patients in the UDCA group took placebo alone.2

      Data on reduction of fatigue and excessive sleepiness with IQIRVO1

      • An analysis of fatigue and sleep via the PRO Measurement Information System (PROMIS) Fatigue Short Form 7a (PROMIS fatigue), PBC-40 fatigue domain, and Epworth Sleepiness Scale (ESS) was performed with patients who completed the ELATIVE double-blind period and entered the OLE1
      • Changes in fatigue/sleepiness were summarized from baseline to week 104 and week 130 with respect to available MCID, categorical changes, and mean change from baseline in total score1

      The data are from a single arm of the OLE study, including only patients on IQIRVO during ELATIVE. No formal statistical analysis was conducted, and results are descriptive only.

      Mean change from baseline in total score of the PROMIS fatigue, PBC-40 fatigue, ESS1,e

      IQIRVO PROMIS fatigue chart IQIRVO PROMIS fatigue chart
      IQIRVO PBC-40 fatigue chart IQIRVO PBC-40 fatigue chart
      IQIRVO ESS fatigue chart IQIRVO ESS fatigue chart

      ePatients included are those with non-missing data at baseline and each time point of interest. Moderate-to-severe fatigue was defined as a PROMIS fatigue total score ≥60 or PBC-40 fatigue domain total score ≥29 at baseline. Week 52: n=95, week 104: n=48, week 130: n=26. Excessive sleepiness was defined as ESS total score ≥10 at baseline. Dotted lines reflect MCID for each measure.1

      The safety and tolerability of IQIRVO was studied in the ELATIVE trial2

      aPatients completing the ELATIVE double-blind period were eligible to enter the OLE trial to receive IQIRVO 80 mg daily. Baseline in this OLE crossover arm was defined as the last available measurement before the first OLE IQIRVO dose.1

      bLiver stiffness >10 kPa and/or bridging fibrosis or cirrhosis on histology.1

      ALP=alkaline phosphatase; CI=confidence interval; LS=least squares; MCID=minimal clinically important difference; OLE=open-label extension; PBC=primary biliary cholangitis; SD=standard deviation; SE=standard error; UDCA=ursodeoxycholic acid; ULN=upper limit of normal; WI-NRS=worst itch numeric rating scale.

      References: 1. Data on file. Ipsen Biopharmaceuticals, Inc. 2. IQIRVO [package insert]. Ipsen Biopharmaceuticals, Inc. Cambridge, MA. 3. Kowdley KV, Bowlus CL, Levy C, et al; ELATIVE Study Investigators’ Group. Efficacy and safety of elafibranor in primary biliary cholangitis. N Engl J Med. 2024;390(9):795-805, suppl. 4. ALKP. Mayo Clinic Laboratories. Accessed February 6, 2025. https://www.mayocliniclabs.com/test-catalog/overview/622157#Clinical-and-Interpretive.  5. BILI3. Mayo Clinic Laboratories. Accessed February 6, 2025. https://www.mayocliniclabs.com/test-catalog/overview/8452#Clinical-and-Interpretive.  6. Hirschfield GM, Chazouillères O, Cortez-Pinto H, et al. A consensus integrated care pathway for patients with primary biliary cholangitis: a guideline-based approach to clinical care of patients. Expert Rev Gastroenterol Hepatol. 2021;15(8):929-939. 7. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017;67(1):145-172. 8. Kowdley KV, Bowlus CL, Levy C, et al. Application of the latest advances in evidence-based medicine in primary biliary cholangitis. Am J Gastroenterol. 2023;118(2):232-242. 9. Jacoby A, Rannard A, Buck D, et al. Development, validation, and evaluation of the PBC-40, a disease specific health related quality of life measure for primary biliary cirrhosis. Gut. 2005;54(11):1622-1629. 10. Jones D, Carbone M, Invernizzi P, et al. Impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trial. Hepatol Commun. 2023;7(3):e0057. 11. Elman S, Hynan LS, Gabriel V, et al. The 5-D itch scale: a new measure of pruritus. Br J Dermatol. 2010;162(3):587-593.

      Indication and Important Safety Information

      Indication

      IQIRVO® is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA.

      This indication is approved under accelerated approval based on reduction of alkaline phosphatase (ALP). Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

      Limitations of Use

      Use of IQIRVO is not recommended in patients who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy).

      Important Safety Information

      Myalgia, Myopathy, and Rhabdomyolysis: Rhabdomyolysis resulting in acute kidney injury occurred in one IQIRVO-treated patient who had cirrhosis at baseline and was also taking a stable dose of an HMG-CoA reductase inhibitor (statin). Myalgia or myopathy, with or without CPK elevations, occurred in patients treated with IQIRVO alone or treated concomitantly with a stable dose of an HMG-CoA reductase inhibitor. Assess for myalgia and myopathy prior to IQIRVO initiation. Consider periodic assessment (clinical exam, CPK measurement) during treatment with IQIRVO, especially in those who have signs and symptoms of new onset or worsening of muscle pain or myopathy. Interrupt IQIRVO treatment if there is new onset or worsening of muscle pain, or myopathy, or rhabdomyolysis.

      Fractures: Fractures occurred in 6% of IQIRVO-treated patients compared to no placebo-treated patients. Consider the risk of fracture in the care of patients treated with IQIRVO and monitor bone health according to current standards of care.

      Adverse Effects on Fetal and Newborn Development: IQIRVO may cause fetal harm when administered during pregnancy. For females of reproductive potential, verify that the patient is not pregnant prior to initiation of therapy. Advise females of reproductive potential to use effective non-hormonal contraceptives or add a barrier method when using systemic hormonal contraceptives during treatment with IQIRVO and for 3 weeks following the last dose of IQIRVO.

      Drug-Induced Liver Injury: Drug-induced liver injury occurred in one patient who took IQIRVO 80 mg once daily and two patients who took IQIRVO at 1.5-times the recommended dosage, of which one presented with autoimmune-like hepatitis. The median time to onset of elevation in liver tests was 85 days. Obtain baseline clinical and laboratory assessments at treatment initiation with IQIRVO and monitor thereafter according to routine patient management. Interrupt IQIRVO treatment if liver tests (ALT, AST, total bilirubin [TB], and/or alkaline phosphatase [ALP]) worsen, or the patient develops signs and symptoms consistent with clinical hepatitis (e.g., jaundice, right upper quadrant pain, eosinophilia). Consider permanent discontinuation if liver tests worsen after restarting IQIRVO.

      Hypersensitivity Reactions: Hypersensitivity reactions have occurred in a clinical trial with IQIRVO at 1.5-times the recommended dosage. Three patients (0.2%) had rash or unspecified allergic reaction that occurred 2 to 30 days after IQIRVO initiation. Hypersensitivity reactions resolved after discontinuation of IQIRVO and treatment with steroids and/or antihistamines. If a severe hypersensitivity reaction occurs, permanently discontinue IQIRVO. If a mild or moderate hypersensitivity reaction occurs, interrupt IQIRVO and treat promptly. Monitor the patient until signs and symptoms resolve. If a hypersensitivity reaction recurs after IQIRVO rechallenge, then permanently discontinue IQIRVO.

      Biliary Obstruction: Avoid use of IQIRVO in patients with complete biliary obstruction. If biliary obstruction is suspected, interrupt IQIRVO and treat as clinically indicated.

      Drug-Drug Interactions

      IQIRVO may reduce the systemic exposure of progestin and ethinyl estradiol (CYP3A4 substrates), which may lead to contraceptive failure and/or an increase in breakthrough bleeding. Switch to effective non-hormonal contraceptives or add a barrier method when using hormonal contraceptives during treatment with IQIRVO and for at least 3 weeks after last dose.

      CPK elevation and/or myalgia occurred in patients on IQIRVO monotherapy. Co-administration of IQIRVO and HMG-CoA reductase inhibitors can increase the risk of myopathy. Monitor for signs and symptoms of muscle injury. Consider periodic assessment (clinical exam, CPK) during treatment. Interrupt IQIRVO treatment if there is new onset or worsening of muscle pain or myopathy.

      Co-administration of IQIRVO with rifampin, an inducer of metabolizing enzymes, may reduce the systemic exposure of elafibranor resulting in delayed or suboptimal biochemical response. Monitor the biochemical response (e.g., ALP and bilirubin) when patients initiate rifampin during treatment with IQIRVO.

      Bile acid sequestrants may interfere with IQIRVO absorption and systemic exposure, which may reduce efficacy. Administer IQIRVO at least 4 hours before or after a bile acid sequestrant, or at as great an interval as possible.

      Use in Special Populations

      Pregnancy: Based on data from animal reproduction studies, IQIRVO may cause fetal harm when administered during pregnancy. There are insufficient data from human pregnancies exposed to IQIRVO to allow an assessment of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Report pregnancies to Ipsen Biopharmaceuticals, Inc. adverse event reporting line at 1-855-463-5127 or https://www.ipsen.com/contact-us/.

      Lactation: There are no data available on the presence of IQIRVO or its metabolites in human milk, or on effects of the drug on the breastfed infant or the effects on milk production. IQIRVO is not recommended during breastfeeding and for at least 3 weeks following last dose of IQIRVO because the risk to breastfed child cannot be excluded.

      Females and Males of Reproductive Potential: IQIRVO may cause fetal harm when administered to pregnant women. Verify the pregnancy status of females of reproductive potential prior to initiating IQIRVO. Advise females of reproductive potential to use effective contraception during treatment with IQIRVO and for 3 weeks after the final dose.

      The most common adverse events occurring in ≥10% of patients were weight gain (23%), abdominal pain (11%), nausea (11%), vomiting (11%), and diarrhea (11%).

      You are encouraged to report side effects to FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Ipsen Biopharmaceuticals, Inc. at 1-855-463-5127.

      Please see full Prescribing Information for IQIRVO.