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Press release from Business Wire

Seattle Genetics Announces Initiation of Phase 1/2 Trial of ADCETRIS® (Brentuximab Vedotin) in Combination with Bendamustine for Hodgkin Lymphoma Patients after Initial Relapse

<p class='bwalignc'> <i>Trial Rationale Supported by Encouraging Data Reported on the Activity and Tolerability of ADCETRIS in the Treatment of Salvage HL</i> </p>

Monday, June 10, 2013

Seattle Genetics Announces Initiation of Phase 1/2 Trial of ADCETRIS® (Brentuximab Vedotin) in Combination with Bendamustine for Hodgkin Lymphoma Patients after Initial Relapse

09:00 EDT Monday, June 10, 2013

BOTHELL, Wash. (Business Wire) -- Seattle Genetics, Inc. (Nasdaq:SGEN) today announced the initiation of a phase 1/2 clinical trial evaluating ADCETRIS (brentuximab vedotin) in combination with bendamustine for patients with Hodgkin lymphoma (HL) after first relapse. The multi-phase study is divided into two cohorts to determine the recommended dosing level and tolerability of combination use and to assess the complete remission rate associated with ADCETRIS in combination with bendamustine. Seattle Genetics is the leader in the field of antibody-drug conjugates (ADCs) and ADCETRIS is an ADC directed to CD30, a defining marker of classical HL. ADCETRIS is not approved for salvage HL patients who are deemed eligible for autologous stem cell transplant (ASCT).

“One of the key goals of our broad ADCETRIS clinical development program is to evaluate its use in earlier lines of HL therapy. This trial will assess the ability of ADCETRIS in combination with bendamustine to induce durable complete remissions in second-line treatment of HL patients prior to transplant,” said Clay B. Siegall, Ph.D., President and Chief Executive Officer at Seattle Genetics. “In this treatment setting, single-agent bendamustine has been shown to induce a high rate of remissions with limited durability. Data from an investigator-sponsored trial with single-agent ADCETRIS demonstrated encouraging activity and tolerability in this setting. This trial is designed to determine if the combination can result in durable complete remissions, potentially increasing the number of patients eligible to receive a transplant.”

This phase 1/2 single-arm, open-label clinical trial will evaluate the efficacy and tolerability of ADCETRIS in combination with bendamustine in HL patients after first relapse. Patients will be eligible to receive up to six cycles of ADCETRIS in combination with bendamustine followed by additional single-agent ADCETRIS for up to a total of 16 cycles. As a part of the trial design, after patients receive ADCETRIS plus bendamustine combination therapy, they have the option to pause therapy to receive an ASCT and then resume treatment with single-agent ADCETRIS as consolidation. Bendamustine is an alkylating agent used in the treatment of chronic lymphocytic leukemias and lymphomas. The primary endpoint of the phase 1 cohort is to determine the recommended dosing level of bendamustine in combination with ADCETRIS as well as the safety and tolerability of the combination. The primary endpoint of the phase 2 cohort is to assess the complete remission rate. Key secondary endpoints include best response, duration of response and progression-free survival. The study is expected to enroll up to 50 patients at multiple centers in the United States.

At the 54th American Society of Hematology (ASH) Annual Meeting and Exposition held December 8-11, 2012 in Atlanta, GA, encouraging data were presented from an abstract titled “Brentuximab Vedotin as a First Line Salvage Therapy in Relapsed/Refractory HL” (Abstract #3699). The investigator-sponsored trial was conducted to evaluate ADCETRIS as a salvage therapy for HL. Fourteen patients were evaluated for response and safety and all had relapsed or refractory HL after initial therapy with chemotherapy regimens or a combination of chemotherapy with or without consolidative radiation treatment.

Of the 14 evaluable patients, 12 patients (85.7 percent) had an objective response rate, including seven (50 percent) complete remissions and five (35.7 percent) partial remissions. The most common Grade 1 or 2 adverse events were peripheral sensory neuropathy (42.9 percent), acneiform rash (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), and there were no Grade 4 adverse events. The abstract can be found at www.hematology.org.

More information about the phase 1/2 trial of ADCETRIS in combination with bendamustine, including enrolling centers, is available by visiting www.clinicaltrials.gov.

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 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
  • Phase 2 trial for relapsed or refractory CD30-positive non-Hodgkin lymphomas
  • Phase 2 trial for frontline HL in patients age 60 and older
  • Phase 2 trial for CD30-positive non-lymphoma malignancies

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 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 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.

Adverse Reactions:

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.

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.

Seattle Genetics, Inc.
Investors:
Peggy Pinkston, 425-527-4160
ppinkston@seagen.com
or
Media:
Tricia Larson, 425-527-4180
tlarson@seagen.com

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