- Company to Present 22 Abstracts in Oncology, Including 5 Oral Presentations, Demonstrating Takeda’s Enduring Commitment to Improving the Lives of Patients with Blood Cancers

Cambridge, Mass. and Osaka, JAPAN, November 5, 2020 – Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) today announced that it will present 22 company-sponsored abstracts at the 62nd American Society of Hematology (ASH) Annual Meeting, being held virtually December 5-8, 2020. The company’s scientific research at ASH will identify unique approaches in advancing the treatment of hematologic cancers, illustrative of its commitment to developing and providing transformative solutions for patient needs. Takeda will also be presenting data from its broader hematology portfolio and pipeline at the conference.

“At this year’s ASH, Takeda’s Oncology Research and Development updates underscore our commitment to transform existing treatment paradigms and investigate truly novel approaches that address critical needs for patients living with blood cancers, such as leukemias, lymphomas and myeloma,” said Chris Arendt, Head, Oncology Therapeutic Area Unit, Takeda. “Our pursuit to cure cancer is driven by our commitment to provide life-saving medicines to all patients, including those with limited or ineffective treatment options.”

Key data to be presented include:
•Pevonedistat: A sub-analysis from the Phase 2 Pevonedistat-2001 trial will be presented in an oral session. The analysis, which focused on outcomes of the higher-risk myelodysplastic syndromes (MDS) subgroup of the study, showed that the combination of pevonedistat and azacitidine resulted in longer event-free survival, longer duration of response and delayed transformation to acute myeloid leukemia without increasing myelosuppression, compared to treatment with azacitidine alone. Additionally, the safety profile of pevonedistat and azacitidine in combination was comparable to azacitidine alone. Despite poor outcomes, there have been no novel advances in higher-risk MDS treatment in over 10 years and new, effective therapies with favorable safety profiles that do not worsen myelosuppression are needed.

ICLUSIG® (ponatinib): Data from the interim analysis of the OPTIC trial of ICLUSIG will be presented in an oral session. The data highlighted the revised benefit-risk of ICLUSIG, a third-generation tyrosine kinase inhibitor (TKI), with the use of a response-based dosing regimen in resistant chronic-phase chronic myeloid leukemia (CP-CML) patients, with or without mutations, who have experienced treatment failure with second-generation (2G) TKIs. Another oral presentation will feature a pooled sub-analysis highlighting patients from the PACE and OPTIC trials, comprising the largest patient population evaluation in a post-2G TKI setting. While CP-CML is often manageable, patients who have experienced treatment failure with prior 2G TKI therapy, especially those who are resistant to therapy, suffer from poor long-term outcomes, underscoring that there are still gaps in care for people living with CP-CML.
•NINLARO™ (ixazomib): Results from the TOURMALINE-MM2 trial will be presented in an oral session. The study was designed to evaluate the addition of NINLARO to lenalidomide and dexamethasone in newly diagnosed transplant ineligible multiple myeloma patients. While the trial did not meet the threshold for statistical significance and the primary endpoint of progression-free survival (PFS) was not met, the study found the addition of NINLARO resulted in a 13.5 month increase in median PFS overall. In the prespecified expanded high-risk cytogenetics subgroup, the addition of NINLARO resulted in a median PFS of 23.8 months versus 18.0 months in the placebo arm. Newly diagnosed multiple myeloma patients are in need of additional proteasome inhibitor-based treatment options, as there are currently no approved options that are all-oral.
•ADCETRIS® (brentuximab vedotin): Five-year follow up data from two Phase 3 frontline lymphoma studies will be featured as poster presentations. Data from the ECHELON-1 trial, which evaluated ADCETRIS in combination with doxorubicin, vinblastine and dacarbazine (ADCETRIS+AVD) for previously untreated, stage III/IV Hodgkin lymphoma shows that, with extended follow-up time, the addition of ADCETRIS to AVD demonstrates a robust and sustained treatment benefit, independent of disease stage, International Prognostic Index risk factor score and PET2 status compared to ABVD, the current standard of care. Positive final analyses from ECHELON-2 which evaluated ADCETRIS in combination with CHP (cyclophosphamide, doxorubicin, prednisone) (ADCETRIS+CHP) versus a standard care treatment in frontline treatment of patients with CD30-positive peripheral T-cell lymphoma will also be presented. The safety profile of ADCETRIS in the ECHELON-1 and ECHELON-2 trials were consistent with the established safety profile of ADCETRIS in combination with chemotherapy.

Accepted oncology abstracts include:

Note: all times listed are in Pacific Time

Pevonedistat
•Efficacy and Safety of Pevonedistat Plus Azacitidine Vs Azacitidine Alone in Higher-Risk Myelodysplastic Syndromes (MDS) From Study P-2001 (NCT02610777). Abstract 653. Oral Presentation. Monday, December 7, 2020 – 11:30 a.m.
•A Randomized Phase 2 Study of Pevonedistat, Venetoclax, and Azacitidine Versus Venetoclax Plus Azacitidine in Adults with Newly Diagnosed Acute Myeloid Leukemia (AML) Who Are Unfit for Intensive Chemotherapy. Abstract 988. Poster Presentation. Saturday, December 5, 2020.
•Randomized Phase 2 Trial of Pevonedistat Plus Azacitidine Versus Azacitidine in Higher-Risk Myelodysplastic Syndromes/Chronic Myelomonocytic Leukemia or Low-Blast Acute Myeloid Leukemia: Exploratory Analysis of Patient-Reported Outcomes. Abstract 2191. Poster Presentation. Sunday, December 6, 2020.

ICLUSIG® (ponatinib)
•Efficacy and Safety of Ponatinib (PON) in Patients with Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Who Failed One or More Second-Generation (2G) Tyrosine Kinase Inhibitors (TKIs): Analyses Based on PACE and OPTIC. Abstract 647. Oral Presentation. Monday, December 7, 2020 – 11:30 a.m.
•Outcome by Mutation Status and Line of Treatment in OPTIC, a Dose-Ranging Study of 3 Starting Doses of Ponatinib in Patients with CP-CML. Abstract 48. Oral Presentation. Saturday, December 5, 2020 – 8:15 a.m.
•A Phase 1/2 Study to Evaluate the Safety and Efficacy of Ponatinib with Chemotherapy in Pediatric Patients with Philadelphia Chromosome-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL). Abstract 2842. Poster Presentation. Monday, December 7, 2020.
•Ponatinib Versus Imatinib with Reduced-Intensity Chemotherapy in Patients with Newly Diagnosed Philadelphia Chromosome-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL): PhALLCON Study. Abstract 1026. Poster Presentation. Saturday, December 5, 2020.
•Treatment of Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Using Tyrosine Kinase Inhibitors in Combination with Chemotherapy: A Patient-Centered Benefit-Risk Assessment. Abstract 3471. Poster Presentation. Monday, December 7, 2020.

Multiple Myeloma
•The Phase 3 TOURMALINE-MM2 Trial: Oral Ixazomib, Lenalidomide, and Dexamethasone (IRd) Vs Placebo-Rd for Transplant-Ineligible Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM). Abstract 551. Oral Presentation. Monday, December 7, 2020 – 7:45 a.m.
•Progression-Free Survival (PFS) Benefit Demonstrated and Quality of Life (QoL) Maintained across Age and Frailty Subgroups with the Oral Proteasome Inhibitor (PI) Ixazomib Vs Placebo As Post-Induction Maintenance Therapy in Non-Transplant Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts): Analysis of the TOURMALINE-MM4 Phase 3 Trial. Abstract 1381. Poster Presentation. Saturday, December 5, 2020.
•Prognostic Importance of Measurable Residual Disease (MRD) Kinetics and Progression-Free Survival (PFS) Benefit in MRD+ Patients (Pts) with Ixazomib Vs Placebo As Post-Induction Maintenance Therapy: Results from the Multicenter, Double-Blind, Phase 3 TOURMALINE-MM4 Trial in Non-Transplant Newly Diagnosed Multiple Myeloma (NDMM) Pts. Abstract 2318. Poster Presentation. Sunday, December 6, 2020.
•In-Class Transition (iCT) from Parenteral Bortezomib to Oral Ixazomib Proteasome Inhibitor (PI) Therapy Increases the Feasibility of Long-Term PI Treatment and Benefit for Newly Diagnosed Multiple Myeloma (NDMM) Patients in an Outpatient Setting: Updated Real-World Results from the Community-Based United States (US) MM-6 Study. Abstract 3200. Poster Presentation. Monday, December 7, 2020.
•Effectiveness and Safety of Ixazomib-Based Therapy in Relapsed/Refractory Multiple Myeloma (RRMM) Patients (Pts) Treated Outside the Clinical Trial Setting Via an Early Access Program (EAP) in Europe: Second Interim Analysis of the ‘Use Via Early Access to Ixazomib’ (UVEA-IXA) Study. Abstract 2292. Poster Presentation. Sunday, December 6, 2020.
•Real-Life-Setting Effectiveness of Ixazomib in Combination with Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma: The REMIX Study. Abstract 1377. Poster Presentation. Saturday, December 5, 2020.
•Real-World Treatment Patterns and Outcomes of Proteasome Inhibitor (PI: Bortezomib [V], Carfilzomib [K], or Ixazomib [I])-Lenalidomide/Dexamethasone (Rd)-Triplets By Prior Lenalidomide-Exposure in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Engaged in Routine Care in the United States (US). Abstract 3242. Poster Presentation. Monday, December 7, 2020.
•TAK-573, an Anti-CD38/Attenuated Ifn? Fusion Protein, Has Clinical Activity and Modulates the Ifn? Receptor (IFNAR) Pathway in Patients with Relapsed/Refractory Multiple Myeloma. Abstract 3197. Poster Presentation. Monday, December 7, 2020.
•Mezagitamab Induces Immunomodulatory Effect in Patients with Relapsed/Refractory Multiple Myeloma (RRMM). Abstract 316. Oral Presentation. Sunday, December 6, 2020 – 10:30 a.m.

ADCETRIS® (brentuximab vedotin) and Lymphoma
•Brentuximab Vedotin with Chemotherapy for Patients with Previously Untreated, Stage III/IV Classical Hodgkin Lymphoma: 5-Year Update of the ECHELON-1 Study. Abstract 2973. Poster Presentation. Monday, December 7, 2020.
•The ECHELON-2 Trial: 5-year Results of a Randomized, Double-Blind, Phase 3 Study of Brentuximab Vedotin and CHP (A+CHP) Versus CHOP in Frontline Treatment of Patients with CD30-Positive Peripheral T-Cell Lymphoma. Abstract 1150. Poster Presentation. Saturday, December 5, 2020.
•Nodal Peripheral T-cell Lymphoma with T Follicular-Helper Phenotype: A Different Entity? Results of the Spanish Retrospective REAL-T Study. Abstract 2972. Poster Presentation. Monday, December 7, 2020.
•Results from the International, Multi-Center, Retrospective B-HOLISTIC Study: Describing Treatment Pathways and Outcomes for Classical Hodgkin Lymphoma. Abstract 2979. Poster Presentation. Monday, December 7, 2020.
•Characteristics and Treatment Response of Newly Diagnosed Advanced-Stage and Relapsed/Refractory Hodgkin Lymphoma in Taiwan: A Nationwide Retrospective Study. Abstract 3479. Poster Presentation. Monday, December 7, 2020.

About Pevonedistat

Pevonedistat is a first in class NEDD8-activating enzyme (NAE) inhibitor, which blocks modifications of select proteins. Pevonedistat treatment disrupts cell cycle progression and cell survival, leading to cell death in cancers including leukemias. Pevonedistat in combination with azacitidine demonstrated antitumor activity in preclinical studies and was well tolerated, with promising clinical activity, in a Phase 1 study of patients with AML. Pevonedistat is currently being evaluated in Phase 3 studies as a first-line treatment for patients with HR-MDS, HR-CMML, and AML, who are ineligible (unfit) for transplant or intensive induction chemotherapy and is also being explored in a Phase 2 study in unfit AML in a triple combination with azacitidine and venetoclax.

About ICLUSIG® (ponatinib) tablets

ICLUSIG is a kinase inhibitor targeting BCR-ABL1, an abnormal tyrosine kinase that is expressed in chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). ICLUSIG is a targeted cancer medicine developed using a computational and structure-based drug-design platform, specifically designed to inhibit the activity of BCR-ABL1 and its mutations. ICLUSIG inhibits native BCR-ABL1, as well as all BCR-ABL1 treatment-resistant mutations, including the most resistant T315I mutation. ICLUSIG is the only approved TKI that demonstrates activity against the T315I gatekeeper mutation of BCR-ABL1. This mutation has been associated with resistance to all other approved TKIs. ICLUSIG received full approval from the FDA in November 2016. ICLUSIG is indicated for the treatment of adult patients with CP, accelerated phase, or blast phase CML or Ph+ ALL for whom no other TKI therapy is indicated, and treatment of adult patients with T315I-positive CML (chronic phase, accelerated phase, or blast phase) or T315I-positive Ph+ ALL. ICLUSIG is not indicated and is not recommended for the treatment of patients with newly diagnosed chronic phase CML.
IMPORTANT SAFETY INFORMATION (U.S.)

WARNING: ARTERIAL OCCLUSION, VENOUS THROMBOEMBOLISM, HEART FAILURE, and HEPATOTOXICITY

See full prescribing information for complete boxed warning.
•Arterial occlusion has occurred in at least 35% of ICLUSIG® (ponatinib)-treated patients including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures. Patients with and without cardiovascular risk factors, including patients less than 50 years old, experienced these events. Interrupt or stop ICLUSIG immediately for arterial occlusion. A benefit-risk consideration should guide a decision to restart ICLUSIG.
•Venous Thromboembolism has occurred in 6% of ICLUSIG-treated patients. Monitor for evidence of thromboembolism. Consider dose modification or discontinuation of ICLUSIG in patients who develop serious venous thromboembolism.
•Heart Failure, including fatalities occurred in 9% of ICLUSIG-treated patients. Monitor cardiac function. Interrupt or stop ICLUSIG for new or worsening heart failure.
•Hepatotoxicity, liver failure and death have occurred in ICLUSIG-treated patients. Monitor hepatic function. Interrupt ICLUSIG if hepatotoxicity is suspected.

WARNINGS AND PRECAUTIONS
see & read more on
http://www.takeda.com/newsroom/newsreleases/2020/takeda-oncology-demonstrates-leadership-in-hematologic-cancers-at-62nd-american-society-of-hematology-ash-annual-meeting/