-Randomized Phase 3 Clinical Trial with ADCETRIS Demonstrated Statistically Significant Improvement in Progression-Free Survival
-Data Highlighted in ASH Press Program; to be Presented in an Oral Session on Monday, December 8, 2014 at 4:30 p.m. PT
SAN FRANCISCO, CA, December 6, 2014 and OSAKA, Japan, December 8, 2014 – Seattle Genetics, Inc. (Nasdaq: SGEN) and Takeda Pharmaceutical Company Limited (TSE:4502) today reported data demonstrating that Hodgkin lymphoma (HL) patients at risk of relapse following an autologous stem cell transplant (ASCT) who received ADCETRIS (brentuximab vedotin) as consolidation therapy immediately after ASCT had significant improvement in progression-free survival (PFS) compared to patients who received placebo (median of 43 months versus 24 months, respectively; hazard ratio=0.57; p-value=0.001). The data from the AETHERA trial were featured at the 56th American Society of Hematology (ASH) Annual Meeting press program today and will be presented in an oral session on December 8, 2014. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL. ADCETRIS has been approved in more than 45 countries for the treatment of relapsed or refractory HL and systemic anaplastic large cell lymphoma (sALCL). ADCETRIS is currently not approved in the AETHERA treatment setting.
“Over the past 20 years, no improvement has been shown in the outcomes of patients treated with autologous stem cell transplant regimens for aggressive lymphomas, including Hodgkin lymphoma,” said Craig Moskowitz, M.D.Clinical Director, Division of Hematologic Oncology, Memorial Sloan Kettering Cancer Center. “Approximately half of the patients who undergo an autologous stem cell transplant will relapse, demonstrating a significant need to identify regimens that improve patient outcomes. Data from the AETHERA clinical trial demonstrate that the addition of brentuximab vedotin use in the immediate post-transplant setting resulted in a statistically significant improvement in PFS with a manageable safety profile.”
“The outcome of the AETHERA trial is an important milestone. It demonstrates that early consolidation treatment with ADCETRIS in Hodgkin lymphoma patients at risk of relapse following an autologous transplant can result in a substantial improvement in PFS versus placebo,” said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “We are pleased to share these data with the physician community at ASH. We will be meeting with the FDA soon to discuss the submission of a supplemental Biologics License Application in the first half of 2015 seeking approval in this consolidation setting.”
“The AETHERA data provide compelling evidence regarding the potential utility of ADCETRIS as consolidation therapy post-transplant in these Hodgkin lymphoma patients, and we look forward to submitting these data to health authorities around the world,” said Michael Vasconcelles, M.D., Global Head, Oncology Therapeutic Area Unit, Takeda Pharmaceutical Company Limited. “Going forward, we are conducting a robust clinical development program to more fully understand the potential of CD30 targeting with ADCETRIS in frontline disease through our ongoing Phase 3 ECHELON-1 and ECHELON-2 trials in HL and mature T-cell lymphomas.”
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 (Abstract #673, oral presentation at 4:30 p.m. PT on December 8, 2014 at the Moscone Center West Building, 3001-3003-3014-3016)
The Phase 3 AETHERA trial was designed to evaluate the potential of single agent ADCETRIS to extend PFS post-ASCT in patients with HL who have at least one risk factor for progression. In addition to the primary endpoint of PFS, secondary endpoints included overall survival (OS), safety and tolerability. Eligible patients must have had a history of refractory HL, have relapsed within one year from receiving frontline chemotherapy and/or have had disease outside of the lymph nodes at the time of pre-ASCT relapse. These factors are consistently reported to be associated with poor prognosis after transplant. Patients received ADCETRIS or placebo every three weeks for up to approximately one year. This international multi-center trial was conducted at 78 sites in the United States, Eastern and Western Europe and Russia.
Submission of safety data from the AETHERA trial to the FDA is a post-marketing requirement that Seattle Genetics will fulfill in its planned supplemental BLA. Takeda plans to submit data from the AETHERA trial to regulatory agencies in its territories.
Please see Important Safety Information at the end of this press release.
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 more than 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.
Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: HL and non-Hodgkin lymphoma. HL 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 generally expresses CD30.
According to the American Cancer Society, approximately 9,200 cases of HL will be diagnosed in the United States during 2014 and more than 1,200 will die from the disease. Globally, there are more than 62,000 cases of HL diagnosed each year. Although frontline combination chemotherapy can result in durable response rates, up to 30 percent of these patients relapse or are refractory to frontline treatment and have few therapeutic options beyond ASCT.
Seattle Genetics is a biotechnology company focused on the development and commercialization of innovative antibody-based therapies for the treatment of cancer. Seattle Genetics is leading the field in developing antibody-drug conjugates (ADCs), a technology designed to harness the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. The company’s lead product, ADCETRIS® (brentuximab vedotin) is an ADC that, in collaboration with Takeda Pharmaceutical Company Limited, is commercially available for two indications in more than 45 countries, including the U.S., Canada, Japan and members of the European Union. Additionally, ADCETRIS is being evaluated broadly in more than 30 ongoing clinical trials. Seattle Genetics is also advancing a robust pipeline of clinical-stage ADC programs, including SGN-CD19A, SGN-CD33A, SGN-LIV1A, SGN-CD70A, ASG-22ME and ASG-15ME. 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, Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com.
The Takeda Oncology Business Unit, headquartered in Cambridge, MA, is co-located with the leadership of Takeda’s globally-integrated oncology research and development enterprise, overseen by the Oncology Therapeutic Area Unit. Takeda Oncology delivers novel medicines to patients with cancer worldwide through its commitment to science, breakthrough innovation and passion for improving the lives of patients. Takeda Oncology was formerly known as Millennium: The Takeda Oncology Company. Additional information about Takeda Oncology is available through its website, www.takedaoncology.com.
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.
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.
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.
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):
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:
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.
Certain of the statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of ADCETRIS and plans for submission for supplemental regulatory approval to and obtaining regulatory approval from the FDA. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include safety and/or efficacy results of the AETHERA trial in at risk, post-ASCT Hodgkin lymphoma will not be sufficient to gain marketing approval in the United States or any other country, that we will be required to amend our submission for marketing approval or that such submission will be refused. In addition, our regulatory plans may change as a result of consultation with the FDA. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company’s 10-Q for the quarter ended September 30, 2014 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.
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