ECHELON-1 Data Anticipated in 2017 to 2018 Timeframe-
BOTHELL, Wash. & CAMBRIDGE, Mass., October 27, 2015 – Seattle Genetics, Inc. (Nasdaq: SGEN) and Takeda Pharmaceutical Company Limited (TSE:4502) today announced that the companies have achieved completion of target patient enrollment in the phase 3 ECHELON-1 clinical trial. ECHELON-1 is a randomized trial evaluating ADCETRIS (brentuximab vedotin) as part of a frontline combination chemotherapy regimen in patients with previously untreated advanced classical Hodgkin lymphoma (HL). ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL. ADCETRIS is currently not approved for the frontline treatment of HL.
Patients in ECHELON-1 were randomized to receive either ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine), a recognized standard of care for frontline HL, or a novel combination consisting of ADCETRIS+AVD, which removes bleomycin from the regimen. The trial has enrolled approximately 1,300 patients, although it remains open at select sites to complete enrollment of approximately 20 patients in an additional cohort to fulfill an ex-U.S. regulatory commitment related to measurement of drug levels during treatment (pharmacokinetics). This continued enrollment will not affect the expected timing of data readout from the trial in the 2017 to 2018 timeframe, based on anticipated event rates. The ECHELON-1 trial is being conducted under a Special Protocol Assessment (SPA) agreement from the U.S. Food and Drug Administration (FDA) and the trial also received European Medicines Agency (EMA) scientific advice.
“In the majority of the world, the standard of care for newly diagnosed Hodgkin lymphoma has not changed in more than three decades, and is based on the globally recognized ABVD regimen of four chemotherapy drugs. With the ECHELON-1 clinical trial, our goal is to redefine the standard of care with a novel ADCETRIS-based combination treatment regimen that improves patient outcomes with a manageable safety profile,” said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “We look forward to reporting results from the ECHELON-1 trial to potentially support an ADCETRIS supplemental Biologics License Application seeking a label expansion for use in this setting.”
“Approximately 25 percent of newly diagnosed Hodgkin lymphoma patients do not respond to initial therapy or relapse within the first two years. There is a significant need to identify additional potential therapies in this patient population that may provide a more durable response and fewer incidences of relapse,” said Dirk Huebner, MD, Global Clinical Lead, Takeda Oncology.
Data previously presented at the ASH Annual Meeting in 2012 and 2014 from a phase 1 trial evaluating ADCETRIS plus AVD demonstrated that 24 of 25 patients (96 percent) achieved a complete remission. Long-term follow-up data demonstrated three-year overall survival was 100 percent and three-year failure-free survival was 92 percent. The most common adverse events of any grade occurring in more than 30 percent of patients were neutropenia, nausea, peripheral sensory neuropathy, fatigue, vomiting, diarrhea, insomnia, bone pain, constipation and hair loss.
ECHELON-1 Trial design
The randomized, open-label, phase 3 trial is investigating ADCETRIS+AVD versus ABVD as frontline therapy in patients with advanced classical HL. The primary endpoint is modified progression free survival per independent review facility assessment using the Cheson 2007 Revised Response Criteria for Malignant Lymphoma. Secondary endpoints include overall survival, complete remission and safety. The multi-center trial is being conducted in North America, Europe, South America, Australia, Asia and Africa. The study has enrolled approximately 1,300 patients who had histologically-confirmed diagnosis of Stage III or IV classical HL and had not been previously treated with systemic chemotherapy or radiotherapy. Data from the trial will be available when a pre-specified number of PFS events have occurred.
For more information about the trial, please visit www.clinicaltrials.gov.
About Classical Hodgkin Lymphoma
Lymphoma is a general term for a group of cancers that originate in the lymphatic system and is the most common type of blood cancer. There are two major categories of lymphoma: HL and non-Hodgkin lymphoma. Classical HL is distinguished from other lymphomas by the characteristic presence of CD30-positive Reed-Sternberg cells.
According to the American Cancer Society, approximately 9,050 cases of HL will be diagnosed in the United States during 2015 and more than 1,150 will die from the disease.
According to the Lymphoma Coalition, over 62,000 people worldwide are diagnosed with HL each year and approximately 25,000 people die each year from this cancer.
ADCETRIS is being evaluated broadly in more than 30 ongoing clinical trials, including the phase 3 ALCANZA trial and two additional phase 3 studies, one in frontline classical HL and one in frontline mature T-cell lymphomas, as well as trials in many additional types of CD30-expressing malignancies, including B-cell lymphomas.
ADCETRIS 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 has received approval from the FDA for three indications: (1) regular approval for the treatment of patients with classical HL after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (2) regular approval for the treatment of classical HL patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Health Canada granted ADCETRIS approval with conditions for relapsed or refractory HL and sALCL.
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 has received marketing authorization by regulatory authorities in more than 55 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 is solely responsible for development costs.
About Seattle Genetics
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 a CD30-targeted ADC that, in collaboration with Takeda Pharmaceutical Company Limited, is commercially available in more than 55 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 in CD30-expressing malignancies. Seattle Genetics is also advancing a robust pipeline of clinical-stage programs, including SGN-CD19A, SGN-CD33A, SGN-LIV1A, SGN-CD70A, ASG-22ME, ASG-15ME and SEA-CD40. 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.
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.
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS® (brentuximab vedotin).
ADCETRIS is contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).
Warnings and Precautions
Most Common Adverse Reactions:
ADCETRIS was studied as monotherapy in 160 patients with relapsed classical HL and sALCL in two uncontrolled single-arm 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.
ADCETRIS was studied in 329 patients with classical HL at high risk of relapse or progression post-auto-HSCT in a placebo-controlled randomized trial. The most common adverse reactions (≥20%) in the ADCETRIS-treatment arm (167 patients), regardless of causality, were neutropenia, peripheral sensory neuropathy, thrombocytopenia, anemia, upper respiratory tract infection, fatigue, peripheral motor neuropathy, nausea, cough, and diarrhea.
Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to monomethyl auristatin E (MMAE).
Use in Specific Populations:
MMAE exposure and adverse reactions are increased in patients with moderate or severe hepatic impairment or severe renal impairment. Avoid use.
For additional Important Safety Information, including Boxed WARNING, please see the full Prescribing Information for ADCETRIS at http://www.seattlegenetics.com/pdf/adcetris_USPI.pdf.
ADCETRIS® is indicated for the treatment of adult patients with relapsed or refractory (r/r) CD30+ Hodgkin lymphoma:
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 and commercial potential of ADCETRIS, including ADCETRIS’ potential as a treatment for advanced classical HL, the anticipated timing of data from the ECHELON-1 trial, the anticipated benefits of Seattle Genetics’ ADCETRIS clinical development program, and the potential submission of a supplemental Biologics License Application seeking a label expansion for ADCETRIS use in the ECHELON-1 setting. 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 the risks of adverse events associated with ADCETRIS use, negative or unexpected ADCETRIS clinical trial results even after promising results in earlier company- and investigator-sponsored trials, and adverse regulatory actions affecting ADCETRIS, all of which could result in Seattle Genetics being unable to expand ADCETRIS’ labeled indications of use to the ECHELON-1 or any other settings. Seattle Genetics may also experience delays in the conduct of and obtaining data from the ECHELON-1 and its other clinical trials, in each case for a variety of reasons, including the inherent difficulty and uncertainty of pharmaceutical product development. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption “Risk Factors” included in Exhibit 99.1 to the company’s Current Report on Form 8-K filed with the Securities and Exchange Commission on September 9, 2015. 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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