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IQIRVO elafibranor 80 mg tablets
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IQIRVO elafibranor 80 mg tablets
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The IQIRVO® (elafibranor) 
Effect

The ELATIVE® Phase 3 Trial

ELATIVE 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.1

Placebo + UDCA referred to as “UDCA alone.”

  • IQIRVO was tested in combination with UDCA: 95% (153/161) of patients were receiving concurrent UDCA therapy1
  • ULN for ALP was defined as 104 U/L for women and 129 U/L for men1
ELATIVE trial design schematic desktop ELATIVE trial design schematic mobile
    Patient characteristics

    There were no clinically relevant imbalances in baseline characteristics between IQIRVO and placebo treatment groups.3

    • 96% of patients in the study were female
    • Mean (SD) baseline ALP was 321.3 (±121.9) U/L in patients taking IQIRVO and 323.1 (±198.6) U/L in patients taking UDCA alone
    • Mean (SD) baseline total bilirubin was 0.57 (±0.30) mg/dL in patients taking IQIRVO and 0.55 (±0.29) mg/dL in patients taking UDCA alone
    • Mean liver stiffness was 9.9 kPA in patients taking IQIRVO and 10.7 kPA in patients taking UDCA alone

    Approximately 40% of patients had ALP >3 x ULN at baseline and ~35% started the trial with advanced disease3,a

    13x more patients achieved biochemical response vs UDCA alone1

    Robust treatment response in 51% of patients receiving IQIRVO at week 52 vs 4% on UDCA alone (P<0.0001) (95% CI: 32% to 57%)1

    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 521,b

    51% biochemical response achieved with IQIRVO vs 4% with UDCA 51% biochemical response achieved with IQIRVO vs 4% with UDCA

    Redefine response with the IQIRVO Effect:
    13x more patients achieving biochemical response demonstrates a 47% treatment difference between IQIRVO and UDCA alone1

      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 treatment6
      • Age <45 at diagnosis6,7

      ALP levels

      Patient profile line graph showing ALP decrease over 6 months

      With IQIRVO, 15% of patients were able to achieve ALP normalization, which is associated with improved outcomes in PBC1,8

      71% of patients in a subgroup analysis saw biochemical response3

      Biochemical response at week 52 in patients with ALP ≤3 x ULN at baseline3

      71% of patients ≤3 x ULN achieved biochemical response with IQIRVO 71% of patients ≤3 x ULN achieved biochemical response with IQIRVO
      Blue IQIRVO checkmark icon

      ALP ≤3 x ULN

      71% (n=46/65) of patients
      with baseline ALP ≤3 x ULN saw biochemical response3
      Risk difference: 63% (95% CI: 43% to 74%)

      Blue IQIRVO checkmark icon

      ALP >3 x ULN

      21% (n=9/43) of patients
      with baseline ALP >3 x ULN saw biochemical response3
      Risk difference: 21% (95% CI: 2% to 35%)

        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 profile1

        Review safety and tolerability findings for IQIRVO.

        IQIRVO decreased ALP quickly1,2

        Rapid ALP reduction in just 4 weeks— an effect sustained through 52 weeks1,b

        Mean ALP reduction from baseline of 117 U/L with IQIRVO.3

        22x greater reduction in ALP levels with IQIRVO 22x greater reduction in ALP levels with IQIRVO

        ALP normalization was achieved with IQIRVO1

        ALP normalization at week 521

        ALP normalization at week 52 ALP normalization at week 52
        IQIRVO normalization graphic desktop IQIRVO normalization graphic mobile

        Data on reduction of pruritus with IQIRVO2

        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 study2

        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). Results with IQIRVO were not statistically significant, and therefore, these results are descriptive only.2

        Pruritus impact vs UDCA alone was measured by PBC-40 and 5-D itch scales2,b

        PBC-40 itch domain at week 522

        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.9,11

        5-D itch score at week 522

        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.10

        The safety and tolerability of IQIRVO was studied in the 
        ELATIVE trial1

        aAdvanced disease stage defined as liver stiffness at baseline >10 kPa and/or bridging fibrosis or cirrhosis on histology.2,3

        bSix patients in the IQIRVO group took IQIRVO alone, while 2 patients in the UDCA group took placebo alone.1

        ALP=alkaline phosphatase; CI=confidence interval; LS=least squares; OLE=open-label extension; PBC=primary biliary cholangitis; QoL=quality of life; SD=standard deviation; UDCA=ursodeoxycholic acid; ULN=upper limit of normal; WI-NRS=worst itch numeric rating scale.

        References: 1. IQIRVO [package insert]. Ipsen Biopharmaceuticals, Inc. Cambridge, MA. 2. 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. 3. Data on file. Ipsen Biopharmaceuticals, Inc. 4. ALKI. Mayo Clinic Laboratories. Accessed February 24, 2024. https://www.mayocliniclabs.com/test-catalog/overview/89503#Clinical-and-Interpretive. 5. BILI3. Mayo Clinic Laboratories. Accessed February 24, 2024. 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. Murillo Perez CF, Harms MH, Lindor KD, et al; Global PBC Study Group. Goals of treatment for improved survival in primary biliary cholangitis: treatment target should be bilirubin within the normal range and normalization of alkaline phosphatase. Am J Gastroenterol. 2020;115(7):1066-1074. 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. 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. 11. 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.

        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.