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TMCNet:  Seattle Genetics Highlights ADCETRIS® (Brentuximab Vedotin) Clinical Data at the 2014 Bone Marrow Transplant Tandem Meetings

[February 27, 2014]

Seattle Genetics Highlights ADCETRIS® (Brentuximab Vedotin) Clinical Data at the 2014 Bone Marrow Transplant Tandem Meetings

BOTHELL, Wash. --(Business Wire)--

Seattle Genetics, Inc. (NASDAQ:SGEN) today highlighted ADCETRIS (brentuximab vedotin) data at the 2014 Bone Marrow Transplant (BMT) Tandem Meetings being held February 26 to March 2, 2014, in Dallas, Texas. Presentations included the first report from an ongoing phase 1/2 clinical trial evaluating the combination of ADCETRIS and bendamustine in the treatment of salvage Hodgkin lymphoma (HL). In addition, a poster presentation summarized the clinical trial design and pooled patient demographics from the phase 3 AETHERA trial in patients with increased risk factors for HL progression following autologous stem cell transplant (ASCT). ADCETRIS is an antibody-drug conjugate (ADC (News - Alert)) directed to CD30, which is expressed in classical HL and systemic anaplastic large cell lymphoma (sALCL).

"We are focused on exploring the potential to improve outcomes in earlier lines of HL by incorporating ADCETRIS in novel settings, and the data presented at the 2014 BMT Tandem Meetings illustrate this goal," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development, at Seattle Genetics. "The interim data presented today evaluating ADCETRIS and bendamustine combination therapy in the salvage HL setting are encouraging, showing a complete remission rate of 77 percent, with another 15 percent of patients, who currently remain on treatment, achieving early partial remissions. In addition, a pooled analysis for the overall population in the AETHERA phase 3 clinical trial was presented, including demographic data, baseline disease characteristics and treatment exposure. We look forward to presenting efficacy and safety data from the AETHERA trial in the second half of 2014."

A Phase 1/2 Single-Arm, Open-Label Study to Evaluate the Safety and Efficacy of Brentuximab Vedotin in Combination with Bendamustine for Patients with Hodgkin Lymphoma in the First Salvage Setting: Interim Results (Abstract #230, poster presentation on Wednesday, February 26, 2014, at 6:45 PM CT)

Interim data from an ongoing phase 1/2 clinical trial were reported from 23 patients with HL after first relapse. The multi-phase study was divided into two cohorts to determine the recommended dose and tolerability of ADCETRIS in combination with bendamustine and to assess the complete remission rate associated with combination use. Bendamustine is an alkylating agent used in the treatment of chronic lymphocytic leukemias and lymphomas. In this trial, patients are eligible to receive up to six cycles of ADCETRIS in combination with bendamustine followed by additional single-agent ADCETRIS for 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. The median age of patients enrolled in the trial was 43 years. At the time of data analysis, 23 patients were evaluable for safety and 13 were evaluable for response. Key findings include:

  • After a median of two cycles of therapy, 92 percent of patients evaluable for response (12 of 13 patients) achieved an objective response, including 77 percent (ten patients) with complete remissions and 15 percent (two patients) with partial remissions. At the time of analysis, the two patients with partial remissions had each received two cycles of therapy and treatment was ongoing.
  • At the time of the analysis, seven patients had undergone an ASCT and three had restarted ADCETRIS as monotherapy.
  • The most common adverse events were nausea (57 percent), rash (39 percent), fever (35 percent), fatigue (30 percent) and vomiting (30 percent).
  • The most common Grade 3 or 4 adverse event was lymphopenia (13 percent Grade 3; nine percent Grade 4).
  • Infusion reactions considered related to combination therapy were reported as serious adverse events in six patients and led to treatment discontinuation for three patients. Symptoms included rash, hives, itching, shortness of breath, wheezing, throat tightness, fever, chills and hypotension. As a result, the protocol is being amended to require premedication with corticosteroids and antihistamines.
  • Enrollment is ongoing to include up to 50 patients at multiple centers in the United States. For more information about this trial, visit www.clinicaltrials.gov.

ADCETRIS is not approved for salvage HL patients who are deemed eligible for ASCT.

The AETHERA Trial: An Ongoing Phase 3 Study of Brentuximab Vedotin in the Treatment of Patients at High Risk of Residual Hodgkin Lymphoma Following Autologous Stem Cell Transplant (Abstract #148, poster presentation on Wednesday, February 26, 2014, at 6:45 PM CT)

The AETHERA clinical trial is a randomized, double-blind, placebo-controlled phase 3 study designed to evaluate the potential of DCETRIS to prevent progression post-ASCT in patients with at least one risk factor for lymphoma progression. The primary endpoint is progression-free survival. Randomization was stratified by risk factors at the time of initiating salvage therapy (refractory, relapsed within 12 months or relapsed after 12 months with extranodal involvement) and by response to salvage therapy (complete remission, partial remission or stable disease). The poster presentation reviewed the demographics and baseline disease characteristics of the 329 patients who enrolled in the study. Key findings for the pooled, blinded data include:

  • Regarding response to frontline therapy, 196 patients (60 percent) were refractory, 107 patients (33 percent) relapsed in less than 12 months and 26 patients (eight percent) relapsed after more than 12 months with extranodal disease.
  • Regarding response to salvage treatment pre-ASCT, 125 patients (38 percent) had a complete remission, 111 patients (34 percent) had a partial remission and 93 patients (28 percent) had stable disease.
  • The median number of treatment cycles was 15 (range, 1-16), and approximately half of all patients (49 percent) received the maximum 16 cycles of study treatment.
  • All patients had completed or discontinued treatment as of August 2013; 61 patients (19 percent) discontinued treatment due to an adverse event.
  • Forty-two patients (13 percent) are known to have died, including 37 deaths that occurred after disease progression and one death that occurred within 30 days of the last dose and was considered not disease related.
  • The primary efficacy analysis of the AETHERA phase 3 clinical trial will be reported in the second half of 2014.

ADCETRIS is not approved for HL patients prior to relapse following ASCT.

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 more than 35 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, has been approved for two indications in more than 35 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 (News - Alert)-CD19A, SGN-CD33A, SGN-LIV1A, 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 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 efficacy in these clinical trials 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 September 30, 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.


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