− Analysis showed more than 60 percent of patients achieved longer progression-free survival following treatment with ADCETRIS compared to prior therapy −
Lugano, Switzerland, June 19, 2013 – Takeda Pharmaceutical Company Limited (TSE:4502) and Seattle Genetics, Inc. (NASDAQ: SGEN) today announced data from a post-hoc analysis examining progression-free survival (PFS) following treatment with ADCETRIS® (brentuximab vedotin) versus last prior therapy in patients diagnosed with relapsed or refractory Hodgkin lymphoma (HL) post-autologous stem cell transplant (ASCT) or relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). The data were highlighted during a presentation at the 12th International Conference on Malignant Lymphoma (ICML) being held June 19–22, 2013 in Lugano, Switzerland.
ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL and sALCL.
The post-hoc analysis compared the investigator assessed PFS following ADCETRIS single-agent treatment to the last prior systemic therapy in patients from two pivotal Phase 2 studies. The post-hoc analysis was conducted in patients with relapsed or refractory HL post-ASCT or relapsed or refractory sALCL in the intent-to-treat (ITT) population. It also included prior systemic treatment histories and post-ADCETRIS stem cell transplant experience for each patient in the ITT populations.
“These encouraging data suggest that ADCETRIS may delay disease progression compared to prior therapies that were used in this heavily pretreated patient population,” said John Radford, M.D., Professor of Medical Oncology, University of Manchester, Manchester, UK. “ADCETRIS is a CD30-targeted treatment option for patients with relapsed or refractory HL or relapsed or refractory sALCL that has shown a high overall response rate, including durable complete responses in both of its approved indications.”
Progression-free survival analyses of two pivotal phase 2 studies of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma or systemic anaplastic large-cell lymphoma (Poster #303)
The analysis, presented by Dr. Radford, included:
Relapsed or Refractory HL post-ASCT
- 102 patients (median age 31 years) diagnosed with relapsed or refractory HL post-ASCT received a median of 3.5 (range, 1–13) prior chemotherapy regimens, not including ASCT, prior to enrollment in the study
- 91 percent of patients received doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) as front-line therapy
- Approximately one-half of patients received ifosfamide, carboplatin, etoposide (ICE) as second-line therapy
- There was no discernible pattern in terms of treatment regimens after second-line therapy
- As expected this was a very heavily pretreated population prior to study entry
- 62 percent of patients achieved a longer PFS with ADCETRIS than with their last prior therapy at a median follow-up of 27 months
- Median PFS was 9.3 months (range, 1.2–36.4) with ADCETRIS versus 6.1 months (range, 1.0–110.2) with last prior therapy
- 63 percent of patients who relapsed within six months of their most recent ASCT and 65 percent of patients who relapsed within twelve months of their most recent ASCT achieved a longer PFS with ADCETRIS than with their last prior systemic therapy
- 20 patients underwent a stem cell transplant (STC) after receiving ADCETRIS, including:
- ASCT (1 patient), allogeneic SCT (18 patients), ASCT followed by allogeneic SCT (1 patient)
- 7 patients received a transplant after treatment with ADCETRIS alone
Relapsed or Refractory sALCL
- 58 patients (median age 52 years) diagnosed with relapsed or refractory sALCL received a median of 2 (range, 1–6) prior chemotherapy regimens, not including ASCT, prior to their enrollment into the study
- Cyclophosphamide, hydroxy doxorubicin, Oncovin®, prednisone (CHOP) was the most commonly used regimen (72 percent) in patients, either as first-line induction therapy or as maintenance therapy
- Most agents were given as part of a combination regimen
- 67 percent of patients achieved a longer PFS with ADCETRIS than with their last prior therapy at a median follow-up 22 months
- Median PFS was 19.6 months (range, 0.8–29.0) with ADCETRIS versus 5.9 months (range, 0.3–111.9) with the last prior therapy
- 20 patients underwent a SCT after receiving ADCETRIS, including:
- ASCT (9 patients) and allogeneic SCT (11 patients)
- 17 patients received a transplant after treatment with ADCETRIS alone
Details of the poster presentation are as follows:
- Poster available on June 19, 2013 12:00 PM CET
- Poster #303
- First author: John Radford, M.D., Professor of Medical Oncology, University of Manchester, Manchester, UK
Additional oral and poster presentations featured at ICML about ADCETRIS include:
- Objective responses in relapsed B-cell lymphomas with single-agent brentuximab vedotin
- Poster session on Thursday, June 20, 2013 from 8:30 AM - 6:30 PM CET
- Abstract #304
- First author: Eric D. Jacobsen, M.D., Dana-Farber Cancer Institute, Boston, MA
- ECHELON-2: phase 3 trial of brentuximab vedotin and CHP versus CHOP in the frontline treatment of patients (pts) with CD30+ mature T-cell lymphomas (MTCL)
- Oral session on Friday, June 21, 2013 at 5:25 PM CET
- Abstract #138
- First author: Owen A. O'Connor, M.D., Ph.D., Professor, and Director, Division of Hematology and Medical Oncology at NYU Cancer Institute, New York, NY
- Two-year follow up of patients with relapsed/refractory Hodgkin treated with brentuximab vedotin prior to reduced intensity allogeneic hematopoietic cell transplantation
- Oral session on Saturday, June 22, 2013 at 8:40 AM CET
- Abstract #140
- First author: Robert Chen, M.D., City of Hope National Medical Center. Duarte, CA
- PET-adapted sequential therapy with brentuximab vedotin and augmented-ICE induces FDG-PET normalization in 92% of patients with relapsed and refractory Hodgkin lymphoma
- Oral session on Saturday, June 22, 2013 at 8:50 AM CET
- Abstract #141
- First author: Alison J. Moskowitz, M.D., Memorial Sloan-Kettering Cancer Center, New York, NY
- Safety and efficacy of brentuximab vedotin for treatment of relapsed mature T-/NK-cell lymphomas
- Oral session on Saturday, June 22, 2013 at 10:00 AM CET
- Abstract #152
- First author: Yasuhiro Oki, M.D., Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
About ADCETRIS® (brentuximab vedotin)
ADCETRIS® (brentuximab vedotin) is the first and only targeted CD30 antibody-drug conjugate (ADC) being evaluated in a variety of CD30-expressing malignancies including Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL). The ADC utilizes Seattle Genetics’ proprietary technology, which employs a linker system designed to be stable in the bloodstream but to release monomethyl auristatin E (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 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) the treatment of adult patients with relapsed or refractory sALCL. ADCETRIS also received marketing authorization by regulatory authorities in Switzerland and South Korea.
ADCETRIS was granted accelerated approval by the U.S. Food and Drug Administration (FDA) and approval with conditions from Health Canada for two indications: (1) the treatment of patients with HL after failure of autologous stem cell transplant (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.
Millennium: The Takeda Oncology Company and Seattle Genetics are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and the Takeda Group has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and the Takeda Group are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where the Takeda Group is 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.
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.
About Seattle Genetics
Seattle Genetics is a biotechnology company focused on the development and commercialization of monoclonal antibody-based therapies for the treatment of cancer. The company’s lead program, ADCETRIS (brentuximab vedotin), received accelerated approval from the U.S. Food and Drug Administration in August 2011 and approval with conditions from Health Canada in February 2013 for two indications. In addition, under a collaboration with Millennium: The Takeda Oncology Company, ADCETRIS received conditional approval from the European Commission in October 2012. Seattle Genetics also has four other clinical-stage ADC programs: SGN-75, ASG-5ME, ASG-22ME and SGN-CD19A. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including AbbVie, Agensys (an affiliate of Astellas), Bayer, Celldex, Daiichi Sankyo, Genentech, GlaxoSmithKline, Millennium, Pfizer and Progenics, as well as ADC co-development agreements with Agensys and Genmab. More information can be found at www.seattlegenetics.com.
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. 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.
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.
Patients who are receiving strong CYP3A4 inhibitors concomitantly with ADCETRIS should be closely monitored for adverse reactions.
For additional important safety information, including Boxed WARNING, please see the full U.S. prescribing information for ADCETRIS at www.ADCETRIS.com.
For Seattle Genetics:
Certain of the statements made in this press release are forward looking, such as those, among others, relating to the company’s ongoing clinical trials. Factors that may cause such a difference include that adverse events may occur that require modification or discontinuation of clinical trials. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company’s 10-Q for the quarter ended March 31, 2013 filed with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
Editor’s Note: This press release is also available under the Media section at: www.millennium.com/InTheNews.aspx and http://www.takeda.com/news/.
Takeda Pharmaceutical Company Limited
Corporate Communications Dept. (PR/IR)
Seattle Genetics, Inc.