Seattle Genetics, Inc. (Nasdaq: SGEN) today highlighted multiple ADCETRIS (brentuximab vedotin) data presentations at the 9 th International Symposium on Hodgkin Lymphoma (ISHL) being held October 12-15, 2013 in Cologne, Germany. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed in classical Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL). ADCETRIS was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in August 2011 for relapsed HL and sALCL and conditional marketing authorization by the European Commission in October 2012 for relapsed or refractory HL and sALCL. “Since the last ISHL meeting in 2010, we have made significant progress in advancing ADCETRIS, including approvals in 35 countries to date for the treatment of relapsed HL and sALCL,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “In addition, we are evaluating ADCETRIS broadly in more than 20 ongoing clinical trials, including four global phase 3 trials in earlier lines of therapy for HL and mature T-cell lymphoma, as well as relapsed cutaneous T-cell lymphoma. Our goal is to establish ADCETRIS as the foundation of therapy for CD30-positive malignancies and improve the therapeutic outcome for patients.” Three oral and nine poster presentations at ISHL illustrate the broad clinical development program for ADCETRIS in HL, including data from a phase 1 frontline advanced HL trial and a poster presentation describing the ongoing global phase 3 ECHELON-1 clinical trial in frontline HL. ADCETRIS is currently not approved for use in the treatment of newly diagnosed HL. Frontline HL Data Presentations: Corporate-sponsored Trials “Frontline Therapy with Brentuximab Vedotin Combined with ABVD or AVD in Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma,” (P005) by Dr. Stephen Ansell, Professor of Medicine, Division of Hematology, Mayo Clinic This phase 1 trial was conducted to evaluate ADCETRIS plus the chemotherapy regimen ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine) or ADCETRIS plus AVD, which removes bleomycin, for the treatment of newly diagnosed advanced stage HL patients.
After completing a combination regimen of ADCETRIS plus AVD, 24 of 25 patients (96 percent) achieved a complete remission. Among the patients in the ADCETRIS plus ABVD cohorts, 21 of 22 patients (95 percent) who completed frontline therapy on study achieved a complete remission. The most common adverse events of any grade occurring in more than 30 percent of patients across both treatment regimens were hair loss, constipation, diarrhea, fatigue, insomnia, nausea, neutropenia, peripheral sensory neuropathy, fever and vomiting. As previously reported, pulmonary toxicity was seen in the ADCETRIS plus ABVD cohorts, resulting in a contraindication for the concomitant administration of ADCETRIS and bleomycin. No pulmonary toxicity was observed in the ADCETRIS plus AVD cohort.These data support the enrollment of the ongoing global phase 3 ECHELON-1 trial. The design of the phase 3 trial will be described in a presentation at ISHL, titled “Phase 3 Study of Brentuximab Vedotin Plus Doxorubicin, Vinblastine and Dacarbazine (A+AVD) vs Doxorubicin, Bleomycin, Vinblastine and Dacarbazine (ABVD) as Front-line Treatment for Advanced Classical Hodgkin Lymphoma (HL): The ECHELON-1 Study,” (P017) by Dr. John Radford, Professor of Medical Oncology, University of Manchester. Visit www.clinicaltrials.org for more information about ECHELON-1. Frontline HL Data Presentations: Investigator-sponsored Trials “Brentuximab Vedotin plus AVD as Initial Therapy of Non-Bulky Limited Stage Classical Hodgkin Lymphoma: Interim Analysis of an Ongoing Phase II Trial,” (T035) by Dr. Jeremy Abramson, Director, Center for Lymphoma, Massachusetts General Hospital A phase 2 investigator-sponsored trial evaluating ADCETRIS plus AVD as initial therapy for non-bulky limited stage classical HL is ongoing and expected to evaluate this regimen in 34 patients. Under the trial design, patients receive two cycles of single-agent ADCETRIS followed by ADCETRIS plus AVD. In the interim analysis, 19 patients were enrolled with a median age of 46. Of the 19 patients, 10 achieved a complete remission after four cycles of ADCETRIS plus AVD, seven remain on therapy and two discontinued therapy due to progressive disease or treatment-related death. The most common adverse events of any grade included nausea, peripheral neuropathy, fatigue, abdominal pain, diarrhea and constipation. Grade 3 or higher adverse events included neutropenic fever, peripheral sensory neuropathy and fatigue.
In the phase 1 corporate-sponsored study presented by Dr. Ansell at the 2013 ISHL meeting, 25 patients with advanced untreated HL were treated with ADCETRIS in combination with AVD. Neutropenic fever was manageable with growth factor support and peripheral neuropathy was manageable with dose reductions or delays in the next dose of therapy. No patients who received ADCETRIS plus AVD discontinued treatment due to adverse events.“Sequential Brentuximab Vedotin (BV) with Adriamycin, Vinblastine, and Dacarbazine (AVD) for Older Patients with Untreated Hodgkin Lymphoma: Preliminary Toxicity Findings from a Phase II Window Study,” (T077) by Dr. Andrew Evens, Chief of Hematology/Oncology, Tufts Medical Center In the interim efficacy and toxicity findings of this investigator-sponsored phase 2 trial, seven untreated, advanced stage HL patients were enrolled with a median age of 73 and either stage II or III disease (two patients each) or stage IV disease (three patients). Under the trial design, older HL patients receive two cycles of single-agent ADCETRIS followed by combination chemotherapy. In this interim analysis, after treatment with two cycles of ADCETRIS all patients experienced Grade 3 or higher adverse events, including neutropenia (three patients), diarrhea (three patients), infection (two patients) and pancreatitis (two patients). One patient death occurred due to acute pancreatitis. Enrollment of the study was temporarily suspended but has since re-opened with monitoring of pancreatic enzymes as well as an exclusion criterion for prior history of pancreatitis. Of the seven patients evaluated for efficacy after receiving two doses of ADCETRIS, one patient experienced a complete remission, four patients experienced a partial remission and two patients experienced stable disease. The phase 2 study is ongoing. A corporate-sponsored retrospective analysis of patients age 60 or older with relapsed or refractory CD30-positive hematologic malignancies treated with ADCETRIS was presented at the American Society of Hematology (ASH) 2012 annual meeting. The analysis assessed the efficacy and safety of single-agent ADCETRIS among 22 sALCL patients, 16 HL patients and two patients with other CD30-positive malignancies. Data showed the incidence of adverse events was generally similar in older and younger patients, with peripheral sensory neuropathy, fatigue and anemia appearing to be more common among patients age 60 or older. Adverse events were manageable with dose modifications or delays.
Analysis of data collected from ADCETRIS clinical trials, as well as from the FDA Adverse Events Reporting System (FAERS) database, indicates that the reported incidence of pancreatitis in all patients treated with ADCETRIS is roughly one in 600. Pancreatitis is a known potential risk factor for several products approved by the FDA for use in the lymphoma disease setting.Additional ADCETRIS Presentations:
- “Progression-free Survival (PFS) Analyses of Two Pivotal Phase 2 Studies of Brentuximab Vedotin in Patients with Relapsed or Refractory (RR) Hodgkin Lymphoma (HL) or Systemic Anaplastic Large-cell Lymphoma (sALCL)” (P134, Corporate-sponsored Trial): Poster presentation
- “PET Adapted Sequential Salvage Therapy with Brentuximab Vedotin and Augmented ICE for Transplant Eligible Patients with Relapsed and Refractory Hodgkin Lymphoma” (T128, Investigator-sponsored Trial): Oral presentation
- “Phase 1/2 Study of Brentuximab Vedotin in Pediatric Patients with Relapsed or Refractory (RR) Hodgkin Lymphoma (HL) or Systemic Anaplastic Large-cell Lymphoma (sALCL): Interim Phase 1 Safety and Pharmacokinetic (PK) Data” (P132, Corporate-sponsored Trial): Poster presentation
- “Post-Authorisation Safety Study (PASS) MA25101: An Observational Cohort Study of the Safety of Brentuximab Vedotin in the Treatment of Relapsed or Refractory (RR) CD30+ Hodgkin Lymphoma (HL) and RR Systemic Anaplastic Large Cell Lymphoma (sALCL). The ARROVEN Study” (P149, Corporate-sponsored Trial): Poster presentation
- “Antitumor Activity of Brentuximab Vedotin in Patients with Relapsed or Refractory (RR) Hodgkin Lymphoma (HL) Following Autologous Stem Cell Transplant (ASCT): Meta-analysis Comparison” (P133, Corporate-sponsored Analysis): Poster presentation
- “Brentuximab Vedotin in Relapsed/Refractory (RR) Hodgkin Lymphoma (HL) and RR Systemic Anaplastic Large-cell Lymphoma (sALCL): A Review of International Experience in the Named Patient Program (NPP)” (P139, Corporate-sponsored Analysis): Poster presentation
- “Relapsed/Refractory (RR) Hodgkin Lymphoma (HL) Following Autologous Stem Cell Transplant (ASCT): Burden of Illness and Advancement in Treatment” (P144, Corporate-sponsored Analysis): Poster presentation
- “UK Treatment Pathways and Resource Use Associated with Relapsed/Refractory Hodgkin Lymphoma After Autologous Stem Cell Transplant” (P102, Corporate-sponsored Analysis): Poster presentation
About ADCETRISADCETRIS (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), 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 was granted accelerated approval by the FDA in August 2011 and approval with conditions by Health Canada in February 2013 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. ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for the treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma (HL): (1) following autologous stem cell transplant (ASCT), or (2) following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option. ADCETRIS is indicated for the treatment of adult patients with relapsed or refractory sALCL. See important safety information below. ADCETRIS is being evaluated in more than 20 ongoing clinical trials across both corporate and investigator-sponsored studies. The trials are designed to broadly evaluate the potential of ADCETRIS in earlier lines of its approved indications as well as in many additional types of CD30-positive malignancies, including cutaneous T-cell lymphoma (CTCL), B-cell lymphomas and mature T-cell lymphomas (MTCL). For more information, visit www.clinicaltrials.gov. The clinical trials include:
- ALCANZA, a phase 3 trial in relapsed CD30-positive CTCL
- ECHELON-1, a phase 3 frontline trial in HL
- ECHELON-2, a phase 3 frontline trial in MTCL
About Seattle GeneticsSeattle 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 is also advancing a robust pipeline of clinical-stage ADC programs: SGN-75, ASG-22ME, SGN-CD19A, SGN-CD33A, ASG-15ME and SGN-LIV1A. 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 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 G-CSF support, 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.
- Embryo-fetal toxicity: Fetal harm can occur. Pregnant women should be advised of the potential hazard to the fetus.
Drug Interactions: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.seattlegenetics.com or www.ADCETRIS.com . Certain of the statements made in this press release are forward-looking, such as those, among others, relating to therapeutic potential of ADCETRIS. 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, but are not limited to, risks that data resulting from the ECHELON-1 trial with ADCETRIS will not support approvals in any of the studied indications. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company’s 10-Q for the quarter ended June 30, 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.