Seattle Genetics Highlights Updated Progression-Free Survival and Overall Survival Data from ADCETRIS® (Brentuximab Vedotin) Frontline PTCL Phase 1 Clinical Trial at the ESMO 2014 Congress

BOTHELL, Wash.--(BUSINESS WIRE)--

Seattle Genetics, Inc. SGEN today highlighted ADCETRIS (brentuximab vedotin) data to be presented at the 2014 European Society for Medical Oncology (ESMO) Congress being held September 26-30, 2014 in Madrid, Spain. The data include a two-year durability analysis from a phase 1 clinical trial of ADCETRIS in combination with chemotherapy for the treatment of newly diagnosed peripheral T-cell lymphoma (PTCL) patients, also known as mature T-cell lymphoma (MTCL). 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).

In the phase 1 trial, newly diagnosed patients received ADCETRIS sequentially with the standard treatment in this setting consisting of cyclophosphamide, doxorubicin, vincristine and prednisone (A+CHOP) or in combination with CHP (A+CHP; removing vincristine from CHOP). In the combination arm, patients received ADCETRIS and CHP every three weeks for six cycles. Patients who achieved at least a partial remission after completing six cycles of combination therapy were eligible to receive continued single-agent ADCETRIS for up to ten additional three-week cycles. The primary endpoints of the trial included defining maximum tolerated dose of ADCETRIS in combination with CHP and evaluating safety. Other endpoints included investigator assessment of response, progression-free survival (PFS) and overall survival (OS).

“Peripheral T-cell lymphoma includes a particularly aggressive group of non-Hodgkin lymphomas with relatively few patients achieving long-term remissions, and initial treatment has not changed in decades, typically including a suboptimal regimen of anthracycline-based chemotherapy,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “Maturing data from this phase 1 trial in patients who have advanced or high-risk disease characteristics demonstrate durable progression-free survival and overall survival rates, supporting our belief that this novel ADCETRIS-containing regimen has the potential to redefine the treatment of frontline PTCL. This hypothesis is being tested in our ongoing phase 3 clinical trial, called ECHELON-2.”

As previously reported at the 2013 American Society of Hematology (ASH) annual meeting and published in the Journal of Clinical Oncology, after completing combination therapy in the phase 1 trial, 26 of 26 patients (100 percent) treated with ADCETRIS plus CHP had an objective response, including 23 patients (88 percent) with a complete remission. All 23 patients who achieved a complete remission demonstrated normalized glucose uptake by PET (positron emission tomography) evaluation. The data presentation at the ESMO Congress is an updated two-year durability analysis from the phase 1 trial.

Brentuximab Vedotin in Combination with CHP in Patients with Newly-Diagnosed CD30+ Peripheral T-cell Lymphoma (PTCL): Two-year Follow-up (Abstract #944O, oral presentation on Monday, September 29, 2014 at 14:00 CEST)

Data were reported from 26 patients who received the combination regimen of ADCETRIS plus CHP. The median age of patients was 56 years. Nineteen patients had sALCL, including 16 patients (62 percent) with anaplastic lymphoma kinase (ALK) negative disease, typically associated with a poor prognosis and median PFS of approximately 18 months with a five-year OS of less than 50 percent. Seven patients had a diagnosis of other types of PTCL. The majority of patients had advanced stage disease and/or were considered high risk. The data will be highlighted in an oral presentation by Dr. Michelle Fanale from The University of Texas MD Anderson Cancer Center.

Updated key findings for ADCETRIS in combination with CHP, based on a median observation time of 27.1 months from first dose of therapy, included:

• The estimated two-year PFS rate was 54 percent, with no patients receiving a consolidative stem cell transplant. There have been no progression events since the previous presentation at the ASH annual meeting in December 2013.
• The estimated two-year OS rate was 80 percent.
• The most common treatment-emergent adverse events of any grade occurring in more than 40 percent of patients were peripheral sensory neuropathy, nausea, fatigue, hair loss, diarrhea and shortness of breath.

ADCETRIS is currently not approved as a frontline treatment for PTCL. Based on these results, a global phase 3 study called ECHELON-2 was initiated and is currently enrolling patients. The ECHELON-2 trial is a randomized, double-blind, placebo-controlled, multi-center trial designed to investigate A+CHP versus CHOP as frontline therapy in patients with CD30-positive PTCL. Approximately 300 patients (approximately 150 patients per treatment arm) will be randomized to receive A+CHP or CHOP every three weeks for six to eight cycles.

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 for intravenous injection received accelerated approval from the FDA and approval with conditions from Health Canada for two indications: (1) the treatment of patients with HL 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 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 has received marketing authorization by regulatory authorities in 45 countries. See important safety information below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda will be solely responsible for development costs.

About Seattle Genetics

Seattle Genetics is a biotechnology company focused on the development and commercialization of innovative antibody-based therapies for the treatment of cancer. Seattle Genetics is leading the field in developing antibody-drug conjugates (ADCs), a technology designed to harness the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. The company's lead product, ADCETRIS^® (brentuximab vedotin) is an ADC that, in collaboration with Takeda Pharmaceutical Company Limited, is commercially available for two indications in more than 45 countries, including the U.S., Canada, Japan and members of the European Union. Additionally, ADCETRIS is being evaluated broadly in more than 30 ongoing clinical trials. Seattle Genetics is also advancing a robust pipeline of clinical-stage ADC programs, including SGN-CD19A, SGN-CD33A, SGN-LIV1A, SGN-CD70A, ASG-22ME and ASG-15ME. 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, Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com.

ADCETRIS (brentuximab vedotin) 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. 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, interrupt the infusion. If anaphylaxis occurs, immediately and permanently discontinue the infusion.
• Hematologic toxicities: Grade 3 or 4 anemia, thrombocytopenia and prolonged (≥1 week) severe neutropenia can occur with ADCETRIS. Febrile neutropenia has been reported with ADCETRIS. Monitor complete blood counts prior to each dose of ADCETRIS and consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. Closely monitor patients for fever. If Grade 3 or 4 neutropenia develops, manage by G-CSF support, dose delays, reductions or discontinuation.
• Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia and sepsis/septic shock (including fatal outcomes) have been reported in patients treated with ADCETRIS. Closely monitor patients during treatment for the emergence of possible bacterial, fungal or viral infections.
• Tumor lysis syndrome: Closely monitor patients with rapidly proliferating tumor and high tumor burden.
• 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 (SJS): SJS has been reported with ADCETRIS. If SJS occurs, discontinue ADCETRIS and administer appropriate medical therapy.
• Embryo-fetal toxicity: Fetal harm can occur. Advise pregnant women 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:

Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to MMAE.

Use in Specific Populations:

MMAE exposure is increased in patients with hepatic impairment and severe renal impairment.

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. 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 efficacy in these clinical trials 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 June 30, 2014 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.