Seattle Genetics, Inc. (Nasdaq: SGEN) today summarized ADCETRIS (brentuximab vedotin) data in relapsed Hodgkin lymphoma (HL) and other CD30-positive malignancies from multiple presentations at the 54 th American Society of Hematology (ASH) Annual Meeting and Exposition being held December 8-11, 2012 in Atlanta, GA. Highlights include compelling survival data from long-term follow up in a pivotal clinical trial of ADCETRIS in relapsed or refractory HL and a retrospective comparison of overall survival among patients treated with ADCETRIS to those not treated with ADCETRIS following an autologous stem cell transplant (ASCT). In addition, data describe the activity and tolerability of ADCETRIS in the salvage HL setting from an investigator-sponsored trial and in relapsed patients age 60 or over with CD30-positive malignancies, including HL. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL. "There are more than a dozen data presentations at ASH evaluating the use of ADCETRIS in CD30-positive malignancies and we are very encouraged by both the broad application across multiple hematologic disease areas as well as the encouraging activity associated with ADCETRIS,” said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “The extensive investigator and corporate data presentations at ASH clearly demonstrate the important role ADCETRIS plays in the treatment of relapsed HL and systemic anaplastic large cell lymphoma and the promise of the role it potentially will play in additional future indications.” Long-term Survival Analysis of an Ongoing Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Hodgkin Lymphoma (Abstract #3689) A pivotal, single-arm trial was conducted in 102 relapsed or refractory HL patients after ASCT to assess efficacy and safety of single-agent ADCETRIS. In addition, the trial was designed to determine duration of response, progression-free survival and overall survival. Enrolled patients had received a median of more than three prior chemotherapy regimens.
Data highlights from the long-term survival analysis in the pivotal trial were:
- After a median observation time of approximately 2.5 years from first dose of ADCETRIS, 59 percent of patients (60 of 102 patients) were alive and the median overall survival had not yet been reached.
- The estimated two year survival rate was 65 percent, including 91 percent for patients who achieved a complete remission.
- Improved overall survival and progression-free survival correlated with PET (positron emission tomography) evaluation at Cycle four.
- There was no significant difference in prolonged overall survival in patients whose disease progressed less than or more than one year following ASCT. The only pretreatment factor that was associated with a higher two year survival rate was a baseline ECOG score of 0.
- The most common adverse events of any grade were peripheral sensory neuropathy (47 percent), fatigue (46 percent), nausea (42 percent), upper respiratory tract infection (37 percent) and diarrhea (36 percent).
- Among the most common adverse events of any grade, the most common Grade 3 or 4 adverse events were neutropenia (14 percent Grade 3, 6 percent Grade 4) and peripheral sensory neuropathy (9 percent Grade 3). Other Grade 3 or 4 adverse events occurring in at least five percent of patients were thrombocytopenia (8 percent) and anemia (6 percent).
- Median overall survival following the date of ASCT in ADCETRIS treated patients was 91.49 months compared to 27.99 months in those not treated with ADCETRIS (p<0.0001).
- In an analysis evaluating predictors of patients who achieved a durable complete remission with ADCETRIS, only the stage of disease at initial diagnosis had a significant effect on overall survival.
Data highlights were:
- Of the 14 patients evaluable at the time of this analysis, the objective response rate was 85.7 percent (12 of 14 patients), including 50 percent (seven of 14 patients) with a complete remission and 35.7 percent (five of 14 patients) with a partial remission. Two patients achieved stable disease after four cycles of therapy. No patients developed progressive disease while on treatment.
- At the time of data analysis, a total of seven of 14 patients had undergone stem cell mobilization after the fourth dose of ADCETRIS and 100 percent of these patients achieved complete remission after stem cell transplantation. The other seven patients were still undergoing stem cell mobilization or had not completed ADCETRIS treatment.
- The most common adverse events of Grade 1 or 2 were peripheral sensory neuropathy (42.9 percent), rash acneiform (35.7 percent), AST elevation (28.6 percent) and fatigue (28.6 percent).
- Grade 3 adverse events were rash acneiform (7.1 percent) and urinary tract infection (7.1 percent). There were no Grade 4 adverse events.
Data highlights from the retrospective analysis of ADCETRIS treated patients age 60 and older were:
- Of the 40 patients evaluated, 33 patients (83 percent) had an objective response, including 18 (45 percent) complete remissions and 15 (38 percent) partial remissions.
- Of the 22 patients with sALCL and two patients with other CD30-positive malignancy, all 24 patients (100 percent) achieved an objective response. Of the 16 patients with HL, nine patients (56 percent) achieved an objective response.
- 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.
- The most common adverse events of any grade with an incidence greater than 25 percent were peripheral sensory neuropathy (60 percent), fatigue (58 percent), nausea (38 percent), anemia (30 percent), fever (28 percent), diarrhea (25 percent) and neutropenia (25 percent).
- The most common Grade 3 or 4 adverse events were neutropenia (25 percent), anemia (20 percent), peripheral sensory neuropathy (15 percent), fatigue (10 percent) and thrombocytopenia (10 percent).
ADCETRIS received accelerated approval from the U.S. Food and Drug Administration (FDA) in August 2011 for two indications: (1) the treatment of patients with Hodgkin lymphoma 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 the treatment of adult patients with relapsed or refractory CD30+ 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 systemic anaplastic large cell lymphoma (sALCL). 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 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 generally expresses CD30. 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 U.S. Food and Drug Administration granted accelerated approval of ADCETRIS in August 2011 for two indications. ADCETRIS is being developed in collaboration with Millennium: The Takeda Oncology Company. In addition, Seattle Genetics has three other clinical-stage ADC programs: SGN-75, ASG-5ME and ASG-22ME. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including Abbott, Agensys (an affiliate of Astellas), Bayer, Celldex Therapeutics, 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 in the featured 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 these trials and the risk of adverse events as ADCETRIS advances in 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 September 30, 2012 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.