Seattle Genetics, Inc. (Nasdaq: SGEN) today summarized ADCETRIS (brentuximab vedotin) and CD30 expression data in non-Hodgkin lymphomas and other 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 encouraging interim data from a phase II clinical trial of ADCETRIS in non-Hodgkin lymphoma and long-term follow up from a pivotal clinical trial of ADCETRIS in relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). In addition, investigators presented data describing the expression of CD30 in DLBCL and case studies on ADCETRIS in patients with systemic mastocytosis. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30. “This collection of data from both corporate studies as well as investigator research into CD30 and the clinical role of ADCETRIS in non-Hodgkin lymphomas add to a growing body of evidence that ADCETRIS has potential in a broad array of CD30-positive malignancies,” said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “The numerous data sets at ASH also reinforce our development strategy for the program and overall vision for ADCETRIS in the treatment of patients with significant unmet medical needs.” A Phase II Study of Brentuximab Vedotin in Patients with Relapsed or Refractory CD30-Positive Non-Hodgkin Lymphomas (Abstract #2746) In an ongoing phase II clinical trial, patients with relapsed or refractory CD30-positive non-Hodgkin lymphomas have been enrolled, including DLBCL and several other non-Hodgkin lymphoma subtypes. 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, 73 patients had been enrolled, including 44 with B-cell lymphoma and 29 with T-cell lymphoma. The median number of prior systemic therapies in both lymphoma classifications was two. Key findings include:
- Of 64 patients evaluable for response, 22 patients (34 percent) achieved an objective response, including 12 complete remissions and ten partial remissions.
- In B-cell lymphoma subtypes, 14 of 42 evaluable patients (33 percent) achieved an objective response, including 11 of 25 DLBCL patients (44 percent).
- In T-cell lymphoma subtypes, eight of 22 evaluable patients (36 percent) achieved an objective response, including five of ten angioimmunoblastic T-cell lymphoma patients (50 percent).
- The most common treatment-emergent adverse events of any grade were fatigue (32 percent), neutropenia (26 percent), nausea (25 percent), diarrhea (23 percent) and fever (22 percent).
- The most common Grade 3 or 4 adverse event considered related to ADCETRIS treatment was neutropenia (28 percent). Other Grade 3 or 4 adverse events occurring in two patients (three percent) each included anemia, decreased appetite, hypotension and leukopenia.
- Enrollment is ongoing. For more information about this trial, visit www.clinicaltrials.gov.
Long-term Remissions Observed in an Ongoing Phase II Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma (Abstract #2745)A pivotal, single-arm clinical trial was conducted in 58 relapsed or refractory sALCL patients 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 two prior chemotherapy regimens. Data highlights from long-term patient follow up in the pivotal trial were:
- Median duration of response has not yet been reached for the 34 patients (59 percent) who achieved a complete remission on study, and 18 patients (53 percent) remained in continued complete remission at the time of data analysis.
- Estimated overall survival rate of patients at two years from initiation of ADCETRIS treatment was 63 percent.
- Patients who achieved a complete remission received a median of nine doses of ADCETRIS.
- The most common adverse events of any grade were peripheral neuropathy (57 percent), nausea (40 percent), fatigue (38 percent), fever (34 percent) and diarrhea (29 percent).
- The most common Grade 3 or 4 adverse events occurring in at least five percent of patients included Grade 3 peripheral neuropathy (17 percent), Grade 3 neutropenia (12 percent) and Grade 4 neutropenia (9 percent). Other Grade 3 or 4 adverse events included thrombocytopenia (14 percent) and anemia (7 percent).
These findings support Seattle Genetics’ ongoing evaluation of ADCETRIS as a treatment for DLBCL. A phase II trial for non-Hodgkin lymphoma, including DLBCL, is currently enrolling patients.ADCETRIS is not approved for the treatment of the DLBCL. Anti-CD30 Antibody-Drug Conjugate Brentuximab Vedotin May Be a Promising Treatment Option for Systemic Mastocytosis (SM) (Abstract #2857) Systemic mastocytosis is a clonal proliferation of abnormal mast cells leading to clinical syndromes including aggressive systemic mastocytosis (ASM) and mast cell leukemia. ASM has been shown to express CD30. In this presentation, data describe the outcome of two patients with ASM who had significant clinical benefit from treatment with ADCETRIS. Both patients had a decrease in mast cell bone marrow percentage involvement and density (including one partial remission), as well as improved normal hematopoiesis. The investigator noted that treatment with ADCETRIS was well-tolerated in these patients. ADCETRIS dose level was reduced for one patient due to peripheral neuropathy and neutropenia. ADCETRIS is not approved for the treatment of the systemic mastocytosis. About ADCETRIS 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 was granted accelerated approval by 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 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 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 is 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 FDA 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 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 the featured clinical trials and the risk of adverse events as ADCETRIS advances in such 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.