News Release

Printer Friendly Version View printer-friendly version
<< Back
European Commission Approves Label Variation for ADCETRIS® (Brentuximab Vedotin) to Include Data on Retreatment of Adult Patients with Relapsed or Refractory Hodgkin Lymphoma and Systemic Anaplastic Large Cell Lymphoma (sALCL)

-Approval  is Based on a Phase 2 Multicenter, Open Label Study (SGN 35-006 Part A) whose Data  are Consistent with the Established Safety and Efficacy Profile of ADCETRIS -

Cambridge, Mass. and Osaka,  Japan, January 22, 2016Takeda  Pharmaceutical Company Limited (TSE:4502) today announced that the European  Commission (EC) has approved a Type II variation for ADCETRIS® (brentuximab  vedotin) to include data on the retreatment of adult patients with relapsed or  refractory (R/R) Hodgkin lymphoma or R/R systemic anaplastic large cell  lymphoma (sALCL) who previously responded to ADCETRIS and who later relapse. The  decision from the EC follows a positive opinion from the Committee for  Medicinal Products for Human Use (CHMP) in October 2015.

ADCETRIS  was granted conditional marketing authorization by the EC in 2012 for the  treatment of R/R CD30+ Hodgkin lymphoma following autologous stem cell  transplant (ASCT), or at least two prior therapies when ASCT or multi-agent  chemotherapy is not a treatment option, and for R/R sALCL.

The  SmPC variation includes an update to the clinical sections, including safety, to  include data on retreatment of adult patients who have responded to previous  treatment with ADCETRIS (CR or PR) under the existing indications, but later  relapsed.

The Type  II variation is based on data from the Phase 2 SGN35-006 Part A study that demonstrated  effective anti-tumor responses can be achieved in the majority of R/R Hodgkin  lymphoma and sALCL patients with ADCETRIS retreatment. The safety and efficacy  results from this trial were consistent with the positive profile demonstrated  in the pivotal Phase 2 studies (SGN35-003 and SGN35-004).

"ADCETRIS  has transformed the treatment landscape for relapsed/refractory Hodgkin  lymphoma and sALCL patients in Europe, and has emerged as a most valuable tool  to induce a remission. However, lymphoma is a relentless disease, and relapse  occurs in some of these very difficult to treat patients. Now, with the  opportunity for retreatment, we can offer patients with very limited options  another chance to potentially benefit from ADCETRIS," said Professor Anton  Hagenbeek, M.D., Ph.D., Professor of Hematology, Department of Hematology,  Academic Medical Center in the University of Amsterdam.

"The  EC decision to include data on retreatment in the ADCETRIS label is important in  advancing care for patients battling these diseases," said Dirk Huebner, M.D.,  Executive Medical Director, Oncology Therapeutic Area Unit, Takeda. "We look  forward to continuing our ongoing clinical program of ADCETRIS in Hodgkin  lymphoma and sALCL, as well as in a variety of other forms of lymphoma, with  the goal of bringing this important therapy to patients who might benefit from  it."

For  further details about the EC decision, please visit the EMA website: www.ema.europa.eu/ema.

SGN35-006  Part A Study
The SGN35-006 Part A study, entitled "Treatment with  SGN-35 in patients with CD30-positive hematologic malignancies who have previously participated in an SGN-35 study," was a Phase 2, multicenter,  open-label study. The study was designed to evaluate ADCETRIS retreatment in  patients with Hodgkin lymphoma (20 patients) or sALCL (8 patients) that  recurred after a previous response to ADCETRIS (Part A). Primary objectives  were safety and anti-tumor response. Secondary objectives were duration of tumor control, including duration of response and progression-free survival  (PFS), overall survival (OS) and incidence of anti-therapeutic antibodies  (ATA).

For more information about the trial, please visit www.clinicaltrialsregister.eu.  

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
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  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 proprietary technology by Seattle Genetics. 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 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 Hodgkin lymphoma 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) the treatment of  adult patients with relapsed or refractory systemic anaplastic large cell  lymphoma (sALCL). In January 2016, the European Commission approved a Type II  variation to include data on the retreatment of adult patients with Hodgkin  lymphoma or sALCL who previously responded to ADCETRIS and who later relapse.  ADCETRIS has received marketing authorization by regulatory authorities in more  than 60 countries. See important safety information below.

ADCETRIS is being evaluated broadly in  more than 45 ongoing clinical trials, including the Phase 3 ALCANZA trial and  two additional Phase 3 studies, one in frontline classical Hodgkin lymphoma and  one in frontline mature T-cell lymphomas, as well as trials in many additional  types of CD30-expressing malignancies, including B-cell lymphomas.

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 is solely responsible for development costs.

About Takeda
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.

ADCETRIS Global  Important Safety Information
ADCETRIS® is indicated for the treatment  of adult patients with relapsed or refractory (r/r) CD30+ Hodgkin lymphoma:

     
  1. Following autologous stem cell transplant or
  2.  
  3. 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.

 

# # #

CONTACTS
Japanese Media
Tsuyoshi Tada
tsuyoshi.tada@takeda.com
+81 (0) 3-3278-2417

European Media
Kate Burd
kate.burd@takeda.com
+41 79 514 9533

Media Outside Japan and Europe:
Elizabeth Pingpank
elizabeth.pingpank@takeda.com 
+1-617-444-1495