Seattle Genetics, Inc. (Nasdaq: SGEN) today highlighted multiple ADCETRIS (brentuximab vedotin) data presentations at the 12 th 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, which is expressed in classical Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL), that was granted accelerated approval by the FDA in August 2011 for relapsed HL and relapsed sALCL and conditional marketing authorization by the European Commission in October 2012 for relapsed or refractory HL and relapsed or refractory sALCL. Four oral and two poster presentations at ICML illustrated the broad clinical development program for ADCETRIS, including oral presentations describing the ongoing global phase 3 ECHELON-2 trial in frontline mature T-cell lymphoma (MTCL) and data from a phase 2 trial in patients with relapsed MTCL. In addition, an oral presentation included the first report of data from an investigator-sponsored trial evaluating ADCETRIS in first-relapse HL patients as part of a pre-autologous stem cell transplant regimen. “With last year’s European conditional marketing authorization supporting the use of ADCETRIS as a treatment for patients with relapsed HL and sALCL, this meeting provides us with an opportunity to share important ADCETRIS data with the international physician and patient community as we evaluate ADCETRIS in additional disease settings,” said Clay B. Siegall, Ph.D., President and Chief Executive Officer at Seattle Genetics. “ADCETRIS is being evaluated for the treatment of CD30-positive malignancies in more than 20 ongoing clinical trials, including three global phase 3 trials. We look forward to the ongoing presentation of important data at medical meetings such as ICML, demonstrating the broad therapeutic potential of ADCETRIS.” Oral Presentations PET-adapted Sequential Therapy with Brentuximab Vedotin and Augmented-ICE in Relapsed and Refractory Hodgkin Lymphoma (Abstract #141, oral session on Saturday, June 22, 2013 at 8:50 AM CET) In an ongoing investigator-sponsored phase 2 clinical trial, patients with relapsed or refractory HL have been enrolled to determine whether ADCETRIS can replace the combination chemotherapy regimen ifosfamide, carboplatin and etoposide (ICE) or be used in sequential administration with ICE to increase the rate of pre-transplant FDG-PET normalization (PET-N), which is an important prognostic factor for patients undergoing autologous stem cell transplant (ASCT). At the time of data analysis, 40 patients had been enrolled and 33 patients had completed the treatment program. Key findings presented by Dr. Alison Moskowitz from Memorial Sloan Kettering Cancer Center include:
- Of 33 evaluable patients, 79 percent obtained a complete remission, including ten patients who achieved PET-N following treatment with ADCETRIS alone and 16 patients who achieved PET-N following the entire treatment program of ADCETRIS sequenced with augmented ICE. All 26 patients underwent ASCT. Of the seven patients who remained PET positive after receiving augmented ICE, one patient underwent an ASCT, five patients received radiation therapy followed by ASCT and one patient received additional chemotherapy.
- Of the 33 evaluable patients, 32 received an ASCT.
- The most common adverse events of any grade were rash (70 percent) and neuropathy (45 percent).
- Enrollment is ongoing. For more information about this trial, visit www.clinicaltrials.gov.
Safety and Efficacy of Brentuximab Vedotin for the Treatment of Relapsed Mature T-/NK-Cell Lymphomas (Abstract #152, oral session on Saturday, June 22, 2013 at 10:00 AM CET)In an encore presentation from the 2012 American Society of Hematology (ASH) Annual Meeting, data were highlighted from a subset of patients in an ongoing phase 2 clinical trial evaluating ADCETRIS in CD30-positive non-Hodgkin lymphoma. The trial is designed to assess the antitumor activity, duration of response and safety profile of ADCETRIS in these patients. At the time of data analysis, 29 patients with MTCL had been enrolled, including 11 with angioimmunoblastic T-cell lymphoma (AITL) and 18 with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). The median number of prior systemic therapies in both lymphoma classifications was two. Key findings include:
- Of 22 patients evaluable for response, eight patients (36 percent) achieved an objective response, including six complete remissions and two partial remissions.
- In AITL, five of 10 evaluable patients (50 percent) achieved an objective response, including four complete remissions and one partial remission.
- In PTCL-NOS, three of 12 evaluable patients (25 percent) achieved an objective response, including two complete remissions and one partial remission.
- Of 17 evaluable patients, 82 percent achieved a tumor reduction.
- Of the 29 patients evaluable for safety, the most common treatment-emergent adverse events of any grade were fatigue (24 percent), fever (17 percent), chills (14 percent), decreased appetite (14 percent), peripheral sensory neuropathy (14 percent) and rash (14 percent).
- The most common Grade 3 adverse event was neutropenia (three patients). Other Grade 3 or 4 events occurring in one patient each included chills, decreased appetite, rash, pulmonary edema, increased lipase, confusional state, dyspnea, hypotension, hypoxia, peripheral motor neuropathy and tumor lysis syndrome. Three patient deaths occurred, including one due to acute respiratory distress syndrome and two others that were disease related.
ECHELON-2: Phase 3 Trial of Brentuximab Vedotin and CHP Versus CHOP in the Frontline Treatment of Patients with CD30-positive Mature T-Cell Lymphomas (MTCL) (Abstract #138 oral session on Friday, June 21, 2013 at 5:25 PM CET)Recent phase 1 data presented at the 2012 ASH Annual Meeting demonstrated that ADCETRIS in combination with cyclophosphamide, doxorubicin and prednisone (A+CHP) in the frontline treatment of MTCL was associated with a manageable safety profile and 100 percent objective response rate, including 88 percent complete remissions. A global phase 3 study, called ECHELON-2, is an ongoing randomized, double-blind, placebo-controlled, multi-center trial designed to investigate A+CHP versus cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) as frontline therapy in patients with CD30-expressing MTCL. Approximately 300 patients (150 patients per treatment arm) will be randomized to receive either A+CHP or CHOP for six to eight cycles every three weeks. The primary endpoint is progression-free survival (PFS) per independent review facility assessment using the Revised Response Criteria for malignant lymphoma (Cheson, 2007). Secondary endpoints include overall survival, complete response rate and safety. The trial is being conducted at 130 sites in 14 countries, including in North America, Europe and Asia. ADCETRIS is currently not approved for frontline treatment of MTCL. For more information about ECHELON-2, visit www.clinicaltrials.gov. Additional ADCETRIS Presentations
- Objective Responses in Relapsed B-cell Lymphomas with Single-agent Brentuximab Vedotin (Abstract #304): Poster session Thursday, June 20, 2013 from 8:30 AM – 6:30 PM CET
- 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): Poster session Friday, June 21, 2013 from 8:30 AM – 6:30 PM CET
- Two-Year Follow Up of Patients with Relapsed/Refractory Hodgkin Treated with Brentuximab Vedotin Prior to Reduced Intensity Allogenic Hematopoietic Cell Transplantation (Abstract #140): Oral session on Saturday, June 22, 2013 at 8:40 AM CET
ADCETRIS received accelerated approval from 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 systemic anaplastic large cell lymphoma (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 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. See important safety information below. Seattle Genetics and Millennium 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 will be solely responsible for development costs. 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 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 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.
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 the therapeutic potential of ADCETRIS and initiation of future clinical trials. 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 inability to show sufficient activity in this second-line clinical trial for Hodgkin lymphoma and the risk of adverse events as ADCETRIS advances in other clinical trials. In addition, data from our clinical trials, including our pivotal trials which were the basis for FDA accelerated approval, may not necessarily be indicative of subsequent clinical trial results. 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.