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FOR U.S. HEALTHCARE PROFESSIONALS ONLY

TAZVERIK® AND THE ROLE OF EZH2
IN FOLLICULAR LYMPHOMA (FL)

TAZVERIK® AND THE ROLE OF EZH2 IN FOLLICULAR LYMPHOMA (FL)

A closer look at how TAZVERIK® works

A closer look at how TAZVERIK® works

A closer look at how TAZVERIK® works

Watch the unique mechanism of action to see how TAZVERIK can help reduce aberrant B-cell proliferation, associated with the development of FL.1,2

This information is derived from animal studies and does not demonstrate clinical efficacy and safety.

    Natural State

    EZH2 plays a critical role in normal B-cell development1,3-5

    EZH2 is an epigenetic regulator of B-cell identity in the germinal center1,3

    • EZH2 activity represses the expression of genes involved in differentiation, negative cell cycle regulation, and apoptosis. Thus allowing B cells to proliferate and survive.1,4,6
    • In healthy cells, EZH2 activity is subsequently downregulated to allow for B-cell differentiation and apoptosis.6,7

    EZH2=enhancer of zeste homolog 2.

    Follicular Lymphoma

    EZH2 plays a critical role in follicular lymphoma1,3-5

    B cells locked in a proliferative germinal center state can lead to the accumulation of malignant B cells and the development of FL8

    • FL is caused by heterogenous combinations of oncogenic hits, leading to high EZH2 activity, which may enable persistent epigenetic silencing of the genes involved in differentiation, negative cell cycle regulation, and apoptosis.1,4-6

    EZH2=enhancer of zeste homolog 2.

    With TAZVERIK

    TAZVERIK can help reduce aberrant B-cell proliferation associated with the development of FL1-5,8-10

    • Inhibition of EZH2 activity by TAZVERIK may enable epigenetic expression of genes that allow for germinal center exit.1,2,11
    • Regardless of oncogenic mutation, follicular lymphoma (FL) tumors have a critical dependence on EZH2 for growth and survival.2,12

    This information is derived from animal studies and does not demonstrate clinical efficacy and safety.

     

    EZH2=enhancer of zeste homolog 2.

    References: 1. Béguelin W, Popovic R, Teater M, et al. EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation. Cancer Cell. 2013;23:677-692. 2. TAZVERIK (tazemetostat) Prescribing Information. Cambridge, MA: Epizyme, Inc., July 2020. 3. Velichutina I, Shaknovich R, Geng H, et al. EZH2-mediated epigenetic silencing in germinal center B cells contributes to proliferation and lymphomagenesis. Blood. 2010;116(24):5247-5255. 4. Huet S, Sujobert P, Salles G. From genetics to the clinic: A translational perspective on follicular lymphoma. Nat Rev Cancer. 2018;18:224-239. 5. Lackraj T, Goswami R, Kridel R. Pathogenesis of follicular lymphoma. Best Pract Res Cl Ha. 2018;31:2-14. 6. Lue JK, Amengual JE. Emerging EZH2 inhibitors and their application in lymphoma. Curr Hematol Malig Rep. 2018;13:369-382. 7. Wang GG, Konze KD, Tao J. Polycomb genes, miRNA, and their deregulation in B-cell malignancies. Blood. 2015;125(8):1217-1225. 8. Mamessier E, Broussais-Guillaumot F, Chetaille B, et al. Nature and importance of follicular lymphoma precursors. Haematologica. 2014;9(5):802-810. 9.  Naradikian MS, Scholz JL, Oropallo MA, Cancro MP. Understanding B cell biology. In: Bosch X, Ramos-Casals M, Khamashta MA (eds.). Drugs Targeting B-Cells in Autoimmune Diseases. Springer;2014. 10. Klein U and Dalla-Favera R. Germinal centres: role in B‐cell physiology and malignancy. Nat Rev Immunol. 2008;8(1):22-33. 11. Noushin Mossadegh-Keller, Gabriel Brisou, Alicia Beyou, et al. Human B Lymphomas Reveal Their Secrets Through Genetic Mouse Models. Front Immunol. 2021 Jul 16;12:683597. 12. von Keudell G and Salles G. The role of tazemetostat in relapsed/refractory follicular lymphoma. Ther Adv Hematol. 2021;12:1-8.

    View guidance on dose reductions & modifications for patients taking TAZVERIK.

    DOSE MODIFICATIONS

    Learn about the resources available to eligible patients through IPSEN CARES. Terms and conditions apply.

    IPSEN CARES

    IMPORTANT SAFETY INFORMATION AND INDICATIONS

    Warnings and Precautions

    • Secondary Malignancies

    The risk of developing secondary malignancies is increased following treatment with TAZVERIK. Across clinical trials of 729 adults who received TAZVERIK 800 mg twice daily, myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) occurred in 0.7% of patients. One pediatric patient developed T-cell lymphoblastic lymphoma (T-LBL). Monitor patients long-term for the development of secondary malignancies.

    • Embryo-Fetal Toxicity

    Based on findings from animal studies and its mechanism of action, TAZVERIK can cause fetal harm when administered to pregnant women. There are no available data on TAZVERIK use in pregnant women to inform the drug-associated risk. Administration of tazemetostat to pregnant rats and rabbits during organogenesis resulted in dose-dependent increases in skeletal developmental abnormalities in both species beginning at maternal exposures approximately 1.5 times the adult human exposure (area under the plasma concentration time curve [AUC0‑45h]) at the 800 mg twice daily dose.

    Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAZVERIK and for 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with TAZVERIK and for 3 months after the final dose.

    Adverse Reactions

    In 99 clinical study patients with relapsed or refractory follicular lymphoma receiving TAZVERIK 800 mg twice daily: Serious adverse reactions occurred in 30% of patients who received TAZVERIK. Serious adverse reactions occurring in ≥2% were general physical health deterioration, abdominal pain, pneumonia, sepsis, and anemia. The most common (≥20%) adverse reactions were fatigue (36%), upper respiratory tract infection (30%), musculoskeletal pain (22%), nausea (24%), and abdominal pain (20%).

    Drug Interactions

    Avoid coadministration of strong or moderate CYP3A inhibitors with TAZVERIK. If coadministration of moderate CYP3A inhibitors cannot be avoided, reduce TAZVERIK dose.

    Avoid coadministration of moderate and strong CYP3A inducers with TAZVERIK, which may decrease the efficacy of TAZVERIK.

    Coadministration of TAZVERIK with CYP3A substrates, including hormonal contraceptives, can result in decreased concentrations and reduced efficacy of CYP3A substrates.

    Lactation

    Because of the potential risk for serious adverse reactions from TAZVERIK in the breastfed child, advise women not to breastfeed during treatment with TAZVERIK and for one week after the final dose.

    To report SUSPECTED ADVERSE REACTIONS, contact Ipsen Biopharmaceuticals, Inc. at 1-855-463-5127 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    INDICATIONS

    TAZVERIK is indicated for the treatment of:

    • Adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least 2 prior systemic therapies.
    • Adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options.

    These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

    Please see full Prescribing Information.

     

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    TAZVERIK is a registered trademark of Epizyme, Inc, an Ipsen company.
    IPSEN CARES is a registered trademark of Ipsen S.A.
    All other trademarks and registered trademarks are property of their respective owners.

    TAZVERIK is a registered trademark of Epizyme, Inc, an Ipsen company. IPSEN CARES is a registered trademark of Ipsen S.A. All other trademarks and registered trademarks are property of their respective owners.

    TAZVERIK is a registered trademark of Epizyme, Inc, an Ipsen company.

    IPSEN CARES is a registered trademark of Ipsen S.A.

    All other trademarks and registered trademarks are property of their respective owners.

    ©2023 Ipsen Biopharmaceuticals, Inc. All rights reserved. TAZ-US-000086 05/23

    ©2023 Ipsen Biopharmaceuticals, Inc. All rights reserved. TAZ-US-000086 05/23