Takeda Announces Abstracts for ADCETRIS® (brentuximab vedotin) in Hodgkin Lymphoma, Systemic Anaplastic Large Cell Lymphoma and Ixazomib in Multiple Myeloma to be Presented at 56th American Society of Hematology Annual Meeting

Takeda Pharmaceutical Company Limited (TSE:4502) today announced that abstracts of interest from studies on VELCADE^® (bortezomib), ADCETRIS ^® (brentuximab vedotin) and the investigational oral proteasome inhibitor, ixazomib (MLN9708), are among those that have been accepted for presentation at this year’s American Society of Hematology (ASH) annual meeting to be held December 6-9, 2014 in San Francisco, California.

Data selected for presentation include results from the Phase 3 AETHERA clinical trial evaluating the potential treatment of brentuximab vedotin, a CD30-targeted antibody drug conjugate (ADC), as consolidation therapy immediately following an autologous stem cell transplantation (ASCT) in patients with Hodgkin lymphoma at high risk of relapse or progression. Other presentations will feature long-term (four-year) survival data for ADCETRIS in relapsed or refractory systemic Anaplastic Large Cell Lymphoma (sALCL) and results from a Phase 2 study examining long-term maintenance therapy with oral proteasome inhibitor ixazomib for patients with previously untreated multiple myeloma (MM).

“The data to be presented at this year’s ASH highlight the excellent progress we have made in developing our oncology portfolio. The rapid advancement of the ixazomib program over the last five years underscores the potential of this investigational therapy in extending the power of proteasome inhibition,” said Christophe Bianchi, M.D., President, Global Oncology Business Unit, Takeda. “As ADCETRIS continues to expand its reach across the globe and demonstrate the potential for benefit in new indications, and VELCADE is featured in more than 120 presentations, we are excited about our programs and our continued pursuit to improve the care of patients who currently have limited treatment options.”

“The treatment landscapes for patients with both relapsed or refractory Hodgkin lymphoma as well as patients with systemic Anaplastic Large Cell Lymphoma continue to evolve, and the data to be presented at ASH suggest that ADCETRIS could be an important, and potentially paradigm-changing therapy, for these patients,” said Michael Vasconcelles, M.D., Head, Oncology Therapeutic Area Unit, Takeda. “Further, the ixazomib data to be presented advance our understanding of the established and important role of proteasome inhibition in the treatment of multiple myeloma, and provides useful insight into the long-term management of patients with previously untreated multiple myeloma.”

Takeda’s abstracts of interest at ASH 2014 include:

Brentuximab Vedotin

• The AETHERA Trial: Results of a Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Brentuximab Vedotin in the Treatment of Patients at Risk of Progression Following Autologous Stem Cell Transplant for Hodgkin Lymphoma
  • Presenter: Craig H. Moskowitz, M.D., Memorial Sloan-Kettering Cancer Center, New York, NY
  • Abstract 673, Oral Presentation, Monday, December 8, 2014, 4:30 PM, West Building, 3001-3003-3014-3016 (Moscone Center)

• Four-Year Survival Data from an Ongoing Pivotal Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma
  • Presenter: Barbara Pro, M.D., Thomas Jefferson University, Philadelphia, PA
  • Abstract 3095, Poster Presentation, Sunday, December 7, 2014, 6:00 PM, West Building, Level 1 (Moscone Center)

Ixazomib

• Long-Term Ixazomib Maintenance Is Tolerable and Improves Depth of Response Following Ixazomib-Lenalidomide-Dexamethasone Induction in Patients (Pts) with Previously Untreated Multiple Myeloma (MM): Phase 2 Study Results
  • Presenter: Shaji K. Kumar, M.D., Mayo Clinic, Rochester, MN
  • Abstract 82, Oral Presentation, Sunday, December 7, 2014, 12:45 PM, West Building, 2001-2003-2014-2016 (Moscone Center)

About VELCADE ^®

VELCADE^® (bortezomib) is co-developed by Millennium/Takeda and Janssen Pharmaceutical Companies. Millennium is responsible for commercialization of VELCADE in the U.S.; Janssen Pharmaceutical Companies are responsible for commercialization in Europe and the rest of the world. Takeda Pharmaceutical Company Limited and Janssen Pharmaceutical K.K. co-promote VELCADE in Japan. VELCADE is approved in more than 90 countries and has been used to treat more than 550,000 patients worldwide.

VELCADE: Important Safety Information

VELCADE^® (bortezomib) is 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.

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).  TLSis 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.

These are not all of the possible side effects with VELCADE. Please see the full Prescribing Information for VELCADE for a complete list available at VELCADE.com.

About ADCETRIS ^®

ADCETRIS^® (brentuximab vedotin) is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics' proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS for intravenous injection received accelerated approval from the U.S. Food and Drug Administration and approval with conditions from Health Canada for two indications: (1) the treatment of patients with HL after failure of ASCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates, and (2) the treatment of patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. The indications for ADCETRIS are based on response rate. There are no data available demonstrating improvement in patient-reported outcomes or survival with ADCETRIS.

ADCETRIS was granted 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 HL 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 45 countries. See important safety information below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda will be solely responsible for development costs.

ADCETRIS U.S. Important Safety Information

BOXED WARNING

Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS.

Contraindication:

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.

Adverse Reactions:

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.

Drug Interactions:

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.

For additional important safety information, including Boxed WARNING, please see the full U.S. prescribing information for ADCETRIS at  www.seattlegenetics.com  or  www.ADCETRIS.com .

ADCETRIS Global Important Safety Information

ADCETRIS^® is indicated for the treatment of adult patients with relapsed or refractory (r/r) CD30+ Hodgkin lymphoma (HL):

1. Following autologous stem cell transplant or

2. 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.

About Ixazomib

Ixazomib is an investigational oral, proteasome inhibitor, which is being studied in multiple myeloma and other malignancies. It is the first oral proteasome inhibitor to enter Phase 3 clinical trials. Four global Phase 3 trials are ongoing; TOURMALINE-MM1, investigating ixazomib in combination with lenalidomide and dexamethasone in relapsed and/or refractory MM, TOURMALINE-MM2, investigating ixazomib in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM, TOURMALINE-MM3, investigating ixazomib as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant and TOURMALINE-AL1, investigating ixazomib plus dexamethasone in patients with relapsed or refractory light chain amyloidosis (AL). For additional information on the ongoing Phase 3 studies please visit www.tourmalinetrials.com or www.clinicaltrials.gov.

About Takeda Pharmaceutical Company Limited

Located in Osaka, Japan, Takeda 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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Contact information

Takeda Pharmaceutical Company Limited
Elizabeth Pingpank, +1-617-444-1495
elizabeth.pingpank@takeda.com
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