– Median Overall Survival Not Reached After 26.5 Month Median Follow-up –
– Data to be Presented at the 17th European Hematology Association Annual Meeting –
Seattle Genetics, Inc. (Nasdaq: SGEN) today announced updated survival data from a pivotal clinical trial of single-agent ADCETRIS (brentuximab vedotin) in patients with relapsed or refractory Hodgkin lymphoma (HL) after autologous stem cell transplant (ASCT) showing that the median overall survival has not been reached after a 26.5 month median follow-up. The data will be reported during an oral presentation at the 17th European Hematology Association (EHA) Annual Meeting being held June 14-17, 2012 in Amsterdam, Netherlands. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30.
"Heavily pretreated Hodgkin lymphoma patients who relapse following autologous stem cell transplant often have a poor prognosis and there is a high unmet medical need for effective treatment options," said Scott Smith M.D., Ph.D., Loyola University Medical Center. "These updated overall survival results from the pivotal trial are encouraging and demonstrate that ADCETRIS may play an important role in the treatment of patients with relapsed or refractory disease."
Long-term Follow-up Results of an Ongoing Pivotal Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Hodgkin Lymphoma
A pivotal trial was conducted in 102 patients with relapsed or refractory HL after ASCT. The primary endpoint was objective response rate (ORR) per independent review. The secondary endpoints were complete remission (CR) rate, duration of response, progression-free survival (PFS), overall survival (OS), and safety and tolerability. At the time of the long-term follow-up analysis, the median observation time from first dose was 26.5 months. Data, to be presented by Dr. Smith, include:
- As previously reported, the ORR was 75 percent (76 of 102 patients), with CRs observed in 33 percent of patients (n=34).
- The median OS had not been reached at the time of the analysis. The estimated OS at 24 months was 65 percent.
- The median PFS for all patients was 5.6 months. The median PFS for patients achieving a CR was 29 months.
- As previously reported, the most common (=20 percent) adverse events (AEs) of any grade were peripheral sensory neuropathy (47 percent), fatigue (46 percent), nausea (42 percent), upper respiratory tract infection (37 percent), diarrhea (36 percent), pyrexia (29 percent), neutropenia (22 percent), vomiting (22 percent) and cough (21 percent).
- Of the AEs that were reported in =20 percent of patients, Grade 3 or higher events included neutropenia (20 percent), peripheral sensory neuropathy (9 percent), fatigue (2 percent), pyrexia (2 percent) and diarrhea (1 percent).
Patients received 1.8 milligrams per kilogram of ADCETRIS every 3 weeks as a 30-minute outpatient intravenous infusion for up to 16 cycles. Patients received a median of nine cycles of ADCETRIS while on trial. The median age of patients in the pivotal trial was 31 years. Enrolled patients had received a median of 3.5 (range 1–13) prior cancer-related systemic therapies, excluding ASCT. Seventy-one percent of patients had primary refractory disease, defined in the study protocol as patients who relapsed within three months of attaining CR or failed to achieve a CR, and 42 percent had not responded to their most recent prior therapy.
Details of the oral presentation are as follows:
- Sunday, June 17; 8:30 AM – 8:45 AM Central European Summer Time (CEST)
- Abstract #1109
- Oral presentation in Hall 2
- First author: Scott Smith M.D., Ph.D., Loyola University Medical Center
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 received accelerated approval from the U.S. Food and Drug Administration (FDA) 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 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 is not approved for use outside the United States. The marketing authorization application for ADCETRIS in relapsed or refractory Hodgkin lymphoma and sALCL, filed by Takeda Global Research & Development Centre (Europe), was accepted for review by the European Medicines Agency for review in June 2011.
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.
According to the American Cancer Society, more than 8,800 cases of Hodgkin lymphoma will be diagnosed in the United States during 2012 and approximately 1,300 people will die from the disease. Globally, there are more than 30,000 cases of Hodgkin lymphoma diagnosed each year. Although front-line combination chemotherapy can result in durable response rates, up to 30 percent of these patients relapse or are refractory to front-line treatment and have few therapeutic options beyond ASCT.
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, Bayer, Celldex Therapeutics, Daiichi Sankyo, Genentech, GlaxoSmithKline, Millennium, Pfizer and Progenics, as well as ADC co-development agreements with Agensys, an affiliate of Astellas, and Genmab. More information can be found at www.seattlegenetics.com.
U.S. Important Safety Information
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS.
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.
ADCETRIS was studied as monotherapy in 160 patients in two phase 2 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.
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 future clinical 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 March 31, 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.
Peggy Pinkston, 425-527-4160