Millennium and Takeda Announce European Conditional Marketing Authorization for ADCETRIS® (Brentuximab Vedotin)

− Indicated for use in adult patients with relapsed or refractory CD30 positive Hodgkin lymphoma or relapsed or refractory systemic anaplastic large cell lymphoma –

− First targeted treatment approved for relapsed or refractory CD30 positive Hodgkin lymphoma in over thirty years¹−

CAMBRIDGE, Mass. & OSAKA, Japan--(BUSINESS WIRE)--Millennium: The Takeda Oncology Company and Takeda Pharmaceutical Company Limited (TSE:4502, “Takeda”), today announced that the European Commission (EC) has granted conditional marketing authorization for ADCETRIS^® (brentuximab vedotin) for two indications: (1) the treatment of adult patients with relapsed or refractory CD30 positive Hodgkin lymphoma (HL) following autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) for the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL).

“Conditional marketing authorization by the European Commission signifies an important advancement in the treatment of adult patients with these rare CD30 positive hematological cancers who are relapsed or refractory and previously had limited options.”

On 19 July 2012, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for conditional marketing authorization for ADCETRIS, based on a positive benefit-risk assessment in the above indications. Granting of conditional marketing authorization by the EC means that there are specific obligations to provide additional clinical data at a later stage to confirm the positive benefit-risk balance.

Takeda intends to launch ADCETRIS across Europe, with the first launches planned in the coming weeks.

“ADCETRIS has been shown to offer a high overall response rate, including durable complete responses in both of its indications,” said Professor Andreas Engert, M.D., University Hospital of Cologne, Germany. “Conditional marketing authorization by the European Commission signifies an important advancement in the treatment of adult patients with these rare CD30 positive hematological cancers who are relapsed or refractory and previously had limited options.”

“The European conditional marketing authorization of ADCETRIS represents a significant step in Takeda’s oncology franchise commitment to developing innovative medicines that make a real difference to patients’ lives,” said Trevor Smith, Head of Commercial Operations, Europe & Canada, Takeda Pharmaceuticals. “ADCETRIS is a new targeted therapeutic option for adult patients with relapsed or refractory Hodgkin lymphoma or relapsed or refractory systemic anaplastic large cell lymphoma, and Takeda looks forward to making it available in Europe.”

ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL and sALCL. The marketing authorisation, which will be held by Takeda Global Research & Development Centre (Europe) Ltd, is valid in all EU member states as well as Iceland, Liechtenstein and Norway, and is based on data from clinical trials and other supportive data in relapsed or refractory HL and relapsed or refractory sALCL.

A Summary of Product Characteristics will be available on the EMA website shortly.

About ADCETRIS^® (Brentuximab Vedotin)

ADCETRIS (brentuximab vedotin) is an antibody-drug conjugate (ADC) comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE). 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 was designated as an orphan medicinal product in Europe for both HL and ALCL by the Committee for Orphan Medicinal Products (COMP) on 15 January 2009.

ADCETRIS is a registered trademark of Millennium Pharmaceuticals, Inc.

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

About Hodgkin Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. The Reed-Sternberg cell expresses CD30.

About Anaplastic Large Cell Lymphoma

ALCL is a type of aggressive T-cell lymphoma, comprising about 3 percent of all non-Hodgkin lymphomas (NHL) in adults and between 10 and 30 percent of all NHL in children. There are two distinct forms/types of ALCL, including primary cutaneous ALCL and systemic ALCL (sALCL). sALCL is a clinically aggressive, systemic lymphoma that primarily involves lymph nodes and expresses CD30.

About Millennium

Millennium: The Takeda Oncology Company, a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE, a first-in-class proteasome inhibitor, and has a robust clinical development pipeline of product candidates. Millennium Pharmaceuticals, Inc. was acquired by Takeda Pharmaceutical Company Ltd. in May, 2008. The Company’s research, development and commercialization activities are focused in oncology. Additional information about Millennium is available through its website, www.millennium.com.

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 patients worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate Website, www.takeda.com.

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. Treating physicians should 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, the infusion should be interrupted and appropriate medical management instituted. If anaphylaxis occurs, the infusion should be immediately and permanently discontinued and appropriate medical management instituted.
• Neutropenia: Monitor complete blood counts prior to each dose of ADCETRIS and consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. If Grade 3 or 4 neutropenia develops, manage by dose delays, reductions or discontinuation. Prolonged (≥1 week) severe neutropenia can occur with ADCETRIS.
• Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden are at risk of tumor lysis syndrome and these patients should be monitored closely and appropriate measures taken.
• 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: Stevens-Johnson syndrome has been reported with ADCETRIS. If Stevens-Johnson syndrome occurs, discontinue ADCETRIS and administer appropriate medical therapy.
• Use in pregnancy: Fetal harm can occur. Pregnant women should be advised 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:

Patients who are receiving strong CYP3A4 inhibitors concomitantly with ADCETRIS should be closely monitored for adverse reactions.

¹ Jona A, Younes A. Novel treatment strategies for patients with relapsed classical Hodgkin lymphoma. Blood Rev. 2010;24:233-238.