Ojjaara

— THERAPEUTIC CATEGORIES —
  • Leukemias, lymphomas, and other hematologic cancers
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Ojjaara Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Momelotinib 100mg, 150mg, 200mg; tabs.

    Pharmacological Class

    Kinase inhibitor.

    How Supplied

    Tabs—30

    Storage

    Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

    Manufacturer

    GlaxoSmithKline

    Generic Availability

    NO

    Mechanism of Action

    Momelotinib is an inhibitor of wild type Janus Kinase 1 and 2 (JAK1/JAK2) and mutant JAK2V617F, which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. Momelotinib and its major metabolite (M21) additionally inhibit activin A receptor type 1 (ACVR1), also known as activin receptor like kinase 2 (ALK2), which produces subsequent inhibition of liver hepcidin expression and increased iron availability resulting in increased red blood cell production.

    Ojjaara Indications

    Indications

    Treatment of intermediate- or high-risk myelofibrosis (MF), including primary or secondary MF (post-polycythemia vera [PV] and post-essential thrombocythemia [ET]), in adults with anemia. 

    Ojjaara Dosage and Administration

    Prior to Treatment Evaluations

    Obtain complete CBC with platelets and hepatic panel prior to initiating treatment, periodically during, and as clinically indicated.

    Adult

    Swallow whole. 200mg once daily. Severe hepatic impairment (Child-Pugh Class C): 150mg once daily. Dose modifications for adverse reactions: see full labeling. 

    Children

    Not established.

    Hepatic Impairment

    Severe hepatic impairment: 150mg orally once daily. 

    Mild to moderate hepatic impairment: no dose adjustment.

    Other Modifications

    Discontinue Ojjaara in patients unable to tolerate 100mg once daily.

    Thrombocytopenia

    Baseline platelet count (≥100 × 109/L)

    • Platelet count (20 × 109/L to <50 × 109/L): Reduce daily dose by 50mg from the last given dose.

    • Platelet count (<20 × 109/L): Interrupt treatment until platelets recover to 50 × 109/L. Restart treatment at a daily dose of 50mg below the last given dose.

    Baseline platelet count (≥50 × 109/L to <100 × 109/L)

    • Platelet count (<20 × 109/L): Interrupt treatment until platelets recover to 50 × 109/L: Restart treatment at a daily dose of 50mg below the last given dose.

     

    Baseline platelet count (<50 × 109/L)

    • Platelet count (<20 × 109/L): Interrupt treatment until platelets recover to baseline. Restart treatment at a daily dose of 50mg below the last given dose.

    Neutropenia

    ANC (<50 × 109/L)

    • Interrupt treatment until ANC ≥0.75 × 109/L. Restart Ojjaara at a daily dose of 50mg below the last given dose.

    Hepatotoxicity (unless other apparent causes)

    ALT and/or AST >5 × ULN (or >5 × baseline, if baseline is abnormal) and/or total bilirubin >2 × ULN (or >2 × baseline, if baseline is abnormal)

    • Interrupt treatment until AST and ALT ≤2 × ULN or baseline (if baseline >2 × ULN) and total bilirubin ≤1.5 × ULN or baseline (if baseline >1.5 × ULN). Restart treatment at a daily dose of 50mg below the last given dose. If reoccurrence of ALT or AST elevations >5 × ULN, permanently discontinue treatment.

    Other Non-Hematologic

    Grade 3 or higher

    • Interrupt treatment until toxicity resolves to Grade 1 or lower (or baseline). Restart treatment at a daily dose of 50mg below the last given dose.

    Ojjaara Contraindications

    Not Applicable

    Ojjaara Boxed Warnings

    Not Applicable

    Ojjaara Warnings/Precautions

    Warnings/Precautions

    Risk for serious infections (eg, bacterial, viral, COVID-19); delay starting therapy until active infections resolved. Monitor for infection during treatment. Check hepatitis B serologies in those with HBV infections prior to initiation. Chronic HBV infection; treat and monitor according to guidelines. Risk for thrombocytopenia and neutropenia. Obtain CBCs (including platelets, neutrophils) prior to and during treatment as indicated. Interrupt or reduce dose if thrombocytopenia or neutropenia occurs. Uncontrolled acute and chronic liver disease; delay starting therapy until resolved. Monitor LFTs at baseline, every 6 months during treatment, then periodically as indicated; modify dose if ALT, AST, or bilirubin increases. Consider the risks/benefits esp. in patients with known malignancy, cardiovascular risk factors, or current/past smokers. Evaluate and treat if thrombosis occurs. Severe hepatic impairment. Advise females of reproductive potential to use effective contraception during and for 1 week after the last dose. Pregnancy. Nursing mothers: not recommended (during and for ≥1 week after the last dose). 

    Pregnancy Considerations

    Risk Summary

    • Available data are insufficient to determine whether there is a drug-associated risk for major birth defects or miscarriage.

    Nursing Mother Considerations

    Risk Summary

    • No data on the presence of momelotinib or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production.

    • Do not breastfeed during treatment and for at least 1 week after the last dose.

    Pediatric Considerations

    Safety and efficacy have not been established.

    Hepatic Impairment Considerations

    Severe hepatic impairment: 150mg once daily.

    Mild to moderate hepatic impairment: no dose adjustment.

    Other Considerations for Specific Populations

    Females and Males of Reproductive Potential

    Contraception: Advise females of reproductive potential who are not pregnant to use highly effective contraception during and for at least 1 week after the last dose.

    Ojjaara Pharmacokinetics

    Absorption

    Median time to momelotinib Cmax (Tmax) at steady state: 2 hours post dose.

    Distribution

    Apparent volume of distribution is 984 L. Plasma protein bound: ~91%.

    Metabolism

    Hepatic (CYP3A4, CYP2C8, CYP2C9, CYP2C19, CYP1A2). 

    Elimination

    Fecal (69%), renal (28%). Half-life: 4–8 hours.

    Ojjaara Interactions

    Interactions

    May potentiate BCRP substrates; dose adjustment of substrate may be needed. When concomitant rosuvastatin: give initially 5mg (max 10mg once daily). May be potentiated by OATP1B1/B3 inhibitors; monitor and consider dose adjustments. 

    Ojjaara Adverse Reactions

    Adverse Reactions

    Thrombocytopenia, hemorrhage, diarrhea, fatigue, nausea, bacterial infection, dizziness; HBV reactivation, hepatotoxicity, major adverse cardiovascular events, malignancies. 

    Ojjaara Clinical Trials

    Clinical Trials

    The approval was based on data from the phase 3 MOMENTUM (ClinicalTrials.gov Identifier: NCT04173494) and SIMPLIFY-1 (ClinicalTrials.gov Identifier: NCT01969838) trials. 

    In MOMENTUM, the efficacy and safety of momelotinib was compared with danazol in 195 adults with symptomatic and anemic MF who were previously treated with a JAK inhibitor. 

    Patients were randomly assigned 2:1 to receive an oral daily dose of either momelotinib 200mg or danazol 600mg for 24 weeks, after which patients receiving danazol were allowed to crossover to receive momelotinib.

    Results showed that patients treated with momelotinib met the primary endpoint achieving a total symptom score (TSS) response rate of 25% at week 24 compared with 9% of patients treated with danazol (P <.01). The change from baseline in TSS was -9.4 for the momelotinib arm and -3.1 for the danazol arm (P =.001).

    Additionally, a greater proportion of patients treated with momelotinib achieved the following key secondary endpoints at week 24 compared with danazol, respectively: 

    • Transfusion independence status, defined as not requiring red blood cell transfusion (except in the case of clinically overt bleeding) for at least 12 weeks immediately prior to the end of week 24, with hemoglobin levels of at least 8g/dL: 30% vs 20% (one-sided P =.023).
    • Splenic response rate, defined as a reduction in spleen volume of at least 25% from baseline: 39% vs 6% (P <.0001).
    • Splenic response rate, defined as a reduction in spleen volume of at least 35% from baseline: 22% vs 3% (P =.001).
    • Rate of zero transfusions: 35% vs 17% (P =.001).

    In SIMPLIFY-1, momelotinib was compared with ruxolitinib in a subpopulation of adults with MF who had not previously received a JAK inhibitor. Findings showed that 31.4% (95% CI, 21.8-42.3) of patients treated with momelotinib met the primary endpoint achieving a splenic volume reduction of at least 35% vs 32.6% (95% CI, 23.4-43.0) of those treated with ruxolitinib.

    Ojjaara Note

    Not Applicable

    Ojjaara Patient Counseling

    Patient Counseling

    Infections: May increase the risk of infections. Promptly report any signs and symptoms of infection to a health care provider.

    Thrombocytopenia and Neutropenia: May cause thrombocytopenia and neutropenia, and patients will need to monitor CBC, including platelet and neutrophil counts, before and during treatment. Report any bleeding to a health care provider.

    Hepatotoxicity: May cause hepatotoxicity, and patients will need to monitor liver blood tests before and during treatment.

    Major Adverse Cardiovascular Events (MACE): Events of MACE including myocardial infarction, stroke, and cardiovascular death have been reported in clinical studies with another JAK inhibitor used to treat RA, a condition for which Ojjaara is not indicated. Advise patients, especially current or past smokers and patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events and to report them to their healthcare provider.

    Thrombosis: Events of deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in clinical studies with another JAK-inhibitor used to treat rheumatoid arthritis, a condition for which Ojjaara is not indicated. Report to health care provider if signs or symptoms of a DVT or PE develop.

    Malignancies: Advise patients, especially current or past smokers, that lymphoma and other malignancies (excluding non-melanoma skin cancers (NMSC) have been reported in clinical studies with another JAK inhibitor used to treat rheumatoid arthritis, a condition for which Ojjaara is not indicated.

    Pregnancy: Females should inform their health care provider if pregnancy is known or suspected. Advise females of reproductive potential who are not pregnant to use highly effective contraception during therapy and for 1 week after the last dose.

    Lactation: Do not breastfeed during and for at least 1 week after the last dose.

    Cost Savings Program

    Ojjaara Patient Support

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