Additional Key Presentations on Takeda’s Leading Hematology-Oncology Portfolio to Highlight ADCETRIS (brentuximab vedotin) Five Year Overall Survival Data in Relapsed/Refractory Hodgkin Lymphoma and Pipeline Data
Cambridge, Mass. and Osaka, Japan, November 5, 2015 – Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that it will present Phase 3 data from the TOURMALINE-MM1 ixazomib clinical trial at the 57th American Society of Hematology (ASH) Annual Meeting to be held in Orlando, Florida from December 5 to 8, 2015. A total of 19 company-sponsored abstracts representing the breadth and depth of Takeda’s hematology-oncology portfolio were accepted for presentation at this year’s meeting.
“We are particularly looking forward to this year’s ASH annual meeting. We will be presenting pivotal data on the ixazomib program, as well as the five year overall survival data for ADCETRIS in relapsed/refractory Hodgkin lymphoma,” said Dixie-Lee Esseltine, MD, FRCPC, Vice President, Oncology Therapeutic Area Unit, Takeda. “The success of these two programs, in addition to data we will be presenting on VELCADE and our pipeline, is the realization of decades of commitment to patients with hematological malignancies.”
“This is the first time Phase 3 data will be presented for ixazomib, an oral, once-weekly proteasome inhibitor which, if approved, would enable the first all-oral triplet regimen containing a proteasome inhibitor for the treatment of relapsed/refractory multiple myeloma,” said TOURMALINE-MM1 Principal Investigator Philippe Moreau, M.D., University of Nantes, France. “In working with Takeda Oncology on the evolution of proteasome inhibition, we continue to strive towards providing new options to address the unmet needs of patients with multiple myeloma.”
Ixazomib is the first oral proteasome inhibitor in late stage clinical development. The TOURMALINE-MM1 study is an international, randomized, double-blind, placebo-controlled Phase 3 clinical trial which was designed to evaluate the superiority of once-a-week oral ixazomib plus lenalidomide and dexamethasone vs. placebo plus lenalidomide and dexamethasone in adult patients with relapsed and/or refractory multiple myeloma.
Ixazomib has been granted Priority Review from the U.S. Food and Drug Administration (FDA) and Accelerated Assessment by the Committee for Medicinal Products for Human Use of the European Medicines Agency , respectively, validating the profound and continuing unmet need for new multiple myeloma treatments. These submissions for the treatment of patients with relapsed and/or refractory multiple myeloma were based on the TOURMALINE-MM1 data.
Takeda’s presentations at ASH 2015 include the following:
- Ixazomib, an Investigational Oral Proteasome Inhibitor (PI), in Combination with Lenalidomide and Dexamethasone (IRd), Significantly Extends Progression-Free Survival (PFS) for Patients (Pts) with Relapsed and/or Refractory Multiple Myeloma (RRMM): The Phase 3 Tourmaline-MM1 Study (NCT01564537)
- Presenter: Philippe Moreau, M.D., University of Nantes, France
- Abstract 727, Oral Presentation, Monday, December 7, 2015, 2:45 PM, Orange County Convention Center, Tangerine 2 (WF2)
- Randomized Phase 2 Study of the All-Oral Combination of Investigational Proteasome Inhibitor (PI) Ixazomib Plus Cyclophosphamide and Low-Dose Dexamethasone (ICd) in Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) Who Are Transplant-Ineligible (NCT02046070)
- Presenter: Meletios A. Dimopoulos, MD, University Athens School of Medicine, Athens, Greece
- Abstract 26, Oral Presentation, Saturday, December 5, 2015, 7:45 AM, Orange County Convention Center, Tangerine (WF2)
ADCETRIS (Brentuximab vedotin)
- Five-year Survival Data Demonstrating Durable Responses from a Pivotal Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Hodgkin Lymphoma
- Presenter: Robert Chen, MD, City of Hope National Medical Center, Duarte, CA
- Abstract 2736, Poster, Sunday, December 6, 2015, 6:00 PM, Orange County Convention Center, Hall A, Level 2
- Updated Efficacy and Safety Data from the AETHERA Trial of Consolidation with Brentuximab Vedotin after Autologous Stem Cell Transplant (ASCT) in Hodgkin Lymphoma Patients at High Risk of Relapse
- Presenter: John Sweetenham, MD, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
- Abstract 3172, Poster, Sunday, December 6, 2015, 6:00 PM, Orange County Convention Center, Hall A, Level 2
- Randomized Phase 2 Open-Label Study of R-CHOP ± Bortezomib in Patients (Pts) with Untreated Non-Germinal Center B-Cell-like (Non-GCB) Subtype Diffuse Large Cell Lymphoma (DLBCL): Results from the Pyramid Trial (NCT00931918)
- Presenter: John P. Leonard, MD, New York Presbyterian Hospital
- Abstract 811, Oral Presentation, Monday, December 7, 2015, 4:30 PM, Orange County Convention Center, Tangerine 3 (WF3-4)
- First Multicenter, Randomized Phase 3 Study in Patients (Pts) with Relapsed/Refractory (R/R) Peripheral T-Cell Lymphoma (PTCL): Alisertib (MLN8237) Versus Investigator's Choice (Lumiere trial; NCT01482962)
- Presenter: Owen O’Connor, MD, Center for Lymphoid Malignancies, Columbia University Medical Center, New York Presbyterian Hospital, New York, NY
- Abstract 341, Oral Presentation, Sunday, December 6, 2015, 5:30 PM, Orange County Convention Center, Hall E2
Ixazomib is an investigational oral proteasome inhibitor which is being studied in multiple myeloma, systemic light-chain (AL) amyloidosis, and other malignancies. Ixazomib was granted orphan drug designation in multiple myeloma in both the United States and Europe in 2011 and for AL amyloidosis in both the U.S. and Europe in 2012. Ixazomib received Breakthrough Therapy status by the U.S. FDA for relapsed or refractory AL amyloidosis in 2014. It is also the first oral proteasome inhibitor to enter Phase 3 clinical trials.
Ixazomib’s clinical development program further reinforces Takeda’s ongoing commitment to developing innovative therapies for people living with multiple myeloma worldwide and the healthcare professionals who treat them. Five global Phase 3 trials are ongoing:
- TOURMALINE-MM1, investigating ixazomib vs. placebo, in combination with lenalidomide and dexamethasone in relapsed and/or refractory multiple myeloma
- TOURMALINE-MM2, investigating ixazomib vs. placebo, in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma
- TOURMALINE-MM3, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed multiple myeloma following induction therapy and autologous stem cell transplant (ASCT)
- TOURMALINE-MM4, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed multiple myeloma who have not undergone ASCT
- TOURMALINE-AL1, investigating ixazomib plus dexamethasone vs. physician choice of selected regimens in patients with relapsed or refractory AL amyloidosis
For additional information on the ongoing Phase 3 studies please visit www.clinicaltrials.gov.
ADCETRIS® (brentuximab vedotin) is an antibody drug conjugate (ADC) which received conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. ADCETRIS has received marketing authorization by regulatory authorities in 55 countries.
ADCETRIS U.S. Important Safety Information
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS.
Concomitant use of ADCETRIS and bleomycin is contraindicated due to pulmonary toxicity.
Warnings and Precautions:
- Peripheral neuropathy: ADCETRIS treatment causes a peripheral neuropathy that is predominantly sensory. Cases of peripheral motor neuropathy have also been reported. ADCETRIS-induced peripheral neuropathy is cumulative. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness and institute dose modifications accordingly.
- Infusion reactions: Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an infusion reaction occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy.
- Hematologic toxicities: Grade 3 or 4 anemia, thrombocytopenia and prolonged (≥1 week) severe neutropenia can occur with ADCETRIS. Febrile neutropenia has been reported with ADCETRIS. Monitor complete blood counts prior to each dose of ADCETRIS and consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. Closely monitor patients for fever. If Grade 3 or 4 neutropenia develops, manage by G-CSF support, dose delays, reductions or discontinuation.
- Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia and sepsis/septic shock (including fatal outcomes) have been reported in patients treated with ADCETRIS. Closely monitor patients during treatment for the emergence of possible bacterial, fungal or viral infections.
- Tumor lysis syndrome: Closely monitor patients with rapidly proliferating tumor and high tumor burden.
- Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death has been reported in ADCETRIS-treated patients. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider the diagnosis of PML in any patient presenting with new-onset signs and symptoms of central nervous system abnormalities. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture or brain biopsy. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
- Stevens-Johnson syndrome (SJS): SJS has been reported with ADCETRIS. If SJS occurs, discontinue ADCETRIS and administer appropriate medical therapy.
- Embryo-fetal toxicity: Fetal harm can occur. Advise pregnant women of the potential hazard to the fetus.
ADCETRIS was studied as monotherapy in 160 patients in two Phase 2 trials. Across both trials, the most common adverse reactions (≥20%), regardless of causality, were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.
Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to MMAE.
Use in Specific Populations
MMAE exposure is increased in patients with hepatic impairment and severe renal impairment. Closely monitor these patients for adverse reactions.
ADCETRIS Global Important Safety Information
ADCETRIS® is indicated for the treatment of adult patients with relapsed or refractory (r/r) CD30+ Hodgkin lymphoma (HL):
- Following autologous stem cell transplant or
- Following at least 2 prior therapies when autologous stem cell transplantation is not a treatment option
ADCETRIS is indicated for the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL).
ADCETRIS is contraindicated for patients who are hypersensitive to ADCETRIS. In addition, combined use of bleomycin and ADCETRIS causes pulmonary toxicity, and is contraindicated.
ADCETRIS can cause serious side effects, including:
- Progressive multifocal leukoencephalopathy (PML): John Cunningham virus (JCV) reactivation resulting in PML and death has been reported in patients treated with ADCETRIS. Patients should be closely monitored for new or worsening neurological, cognitive, or behavioral signs or symptoms, which may be suggestive of PML.
- Pancreatitis: Acute pancreatitis has been observed in patients treated with ADCETRIS. Fatal outcomes have been reported. Patients should be closely monitored for new or worsening abdominal pain.
- Pulmonary Toxicity: Cases of pulmonary toxicity have been reported in patients receiving ADCETRIS. In the event of new or worsening pulmonary symptoms (e.g., cough, dyspnoea), a prompt diagnostic evaluation should be performed.
- Serious infections and opportunistic infections: Serious infections such as pneumonia, staphylococcal bacteraemia, sepsis/septic shock (including fatal outcomes), and herpes zoster, and opportunistic infections such as Pneumocystis jiroveci pneumonia and oral candidiasis have been reported in patients treated with ADCETRIS. Patients should be carefully monitored during treatment for emergence of possible serious and opportunistic infections.
- Infusion-related reactions: Immediate and delayed infusion-related reactions, as well as anaphylaxis, have occurred with ADCETRIS. Patients should be carefully monitored during and after an infusion.
- Tumor lysis syndrome (TLS): TLS has been reported with ADCETRIS. Patients with rapidly proliferating tumor and high tumor burden are at risk of TLS and should be monitored closely and managed according to best medical practice.
- Peripheral neuropathy (PN): ADCETRIS treatment may cause PN that is predominantly sensory. Cases of peripheral motor neuropathy have also been reported. Patients should be monitored for symptoms of PN, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness.
- Hematological toxicities: Grade 3 or Grade 4 anemia, thrombocytopenia, and prolonged (equal to or greater than one week) Grade 3 or Grade 4 neutropenia can occur with ADCETRIS. Complete blood counts should be monitored prior to administration of each dose.
- Febrile neutropenia: Febrile neutropenia has been reported. Patients should be monitored closely for fever and managed according to best medical practice.
- Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN): SJS and TEN have been reported. Fatal outcomes have been reported.
- Hyperglycemia: Hyperglycemia has been reported during trials in patients with an elevated body mass index (BMI) with or without a history of diabetes mellitus. Any patient who experiences an event of hyperglycemia should have their serum glucose closely monitored.
- Renal and hepatic impairment: There is limited experience in patients with renal and hepatic impairment. Population pharmacokinetic analysis indicated that MMAE clearance might be affected by moderate and severe renal impairment, and by low serum albumin concentrations. Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been reported. Liver function should be routinely monitored in patients receiving brentuximab vedotin.
- Sodium content in excipients: This medicinal product contains a maximum of 2.1 mmol (or 47mg) of sodium per dose. To be taken into consideration for patients on a controlled sodium diet.
Serious adverse drug reactions were: neutropenia, thrombocytopenia, constipation, diarrhea, vomiting, pyrexia, peripheral motor neuropathy and peripheral sensory neuropathy, hyperglycemia, demyelinating polyneuropathy, tumor lysis syndrome, and Stevens-Johnson syndrome.
ADCETRIS was studied as monotherapy in 160 patients in two Phase 2 studies. Across both studies, adverse reactions defined as very common (≥1/10) were: infections, neutropenia, peripheral sensory neuropathy, diarrhea, nausea, vomiting, alopecia, pruritis, myalgia, fatigue, pyrexia, and infusion-related reactions. Adverse reactions defined as common (≥1/100 to <1/10) were: upper respiratory tract infection, herpes zoster, pneumonia, anemia, thrombocytopenia, hyperglycemia, peripheral motor neuropathy, dizziness, demyelinating polyneuropathy, cough, dyspnea, constipation, rash, arthralgia, back pain, and chills.
These are not all of the possible side effects with ADCETRIS. Please refer to Summary of Product Characteristics (SmPC) before prescribing.
VELCADE® (bortezomib) is a proteasome inhibitor approved for the treatment of patients with multiple myeloma. VELCADE is also approved for the treatment of patients with mantle cell lymphoma who have already received at least one prior treatment. VELCADE® (bortezomib) is co-developed by Millennium/Takeda and Janssen Pharmaceutical Companies. VELCADE is approved in more than 90 countries and has been used to treat more than 550,000 patients worldwide.
VELCADE: Important Safety Information
Patients should not receive VELCADE if they are allergic to bortezomib, boron or mannitol. VELCADE should not be administered intrathecally. Women should avoid becoming pregnant or breastfeeding while taking VELCADE. Patients with diabetes may require close monitoring and adjustment of their medication. VELCADE can cause serious side effects, including:
- Peripheral neuropathy. Nerve problems, which can be severe including muscle weakness, tingling, burning, pain, or loss of feeling in the hands and feet.
- Low blood pressure. A drop in blood pressure resulting in dizziness, light headedness or fainting.
- Heart problems. Heart rhythm problems and heart failure including worsening of existing conditions. Symptoms may include chest pressure or pain, palpitations, swelling of the ankles or feet, or shortness of breath.
- Lung problems, some of which have been fatal. Symptoms include cough, shortness of breath, wheezing or difficulty breathing.
- Liver problems. Liver failure including a yellow discoloration of the eyes and skin.
- Posterior reversible encephalopathy syndrome (PRES). A rare, reversible condition involving the brain. Symptoms may include seizures, high blood pressure, headaches, tiredness, confusion, blindness, or other vision problems
- Gastrointestinal problems. Nausea, vomiting, diarrhea and constipation.
- Thrombocytopenia and neutropenia. Lowering the levels of blood cells, which could result in a higher risk for infections or bleeding.
- Tumor lysis syndrome (TLS). TLS is a syndrome that causes a chemical imbalance in the blood that could lead to heart and/or kidney problems.
Common side effects seen in patients receiving VELCADE include: fever, decreased appetite, fatigue, rash.
Alisertib (MLN8237) is an oral, selective, inhibitor of Aurora A kinase being investigated by Takeda for the treatment of small cell lung cancer. Aurora A kinase is required for cells to divide properly and has been shown to be over-expressed in a variety of cancers, and inhibition of Aurora A kinase represents a novel approach in cancer research.
Located in Osaka, Japan, Takeda (TSE: 4502) is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for people worldwide through leading innovation in medicine.
Additional information about Takeda is available through its corporate website, www.takeda.com.
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