Seattle Genetics Completes Enrollment In Phase III ALCANZA Clinical Trial Evaluating ADCETRIS (Brentuximab Vedotin) In CD30-Expressing Cutaneous T-Cell Lymphoma (CTCL)

-Results from Two Investigator-Sponsored Phase 2 Clinical Trials Recently Published in the Journal of Clinical Oncology Evaluating ADCETRIS in Patients with Relapsed CTCL Demonstrate 70 Percent or Greater Objective Response Rate-

-ALCANZA Data Anticipated in Second Half of 2016-

BOTHELL, Wash.--(BUSINESS WIRE)--Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that the company and its collaborator, Takeda Pharmaceutical Company Limited (Takeda), completed patient enrollment in the phase 3 ALCANZA clinical trial. ALCANZA is a randomized trial evaluating ADCETRIS (brentuximab vedotin) versus investigator’s choice of methotrexate or bexarotene in 132 patients with CD30-expressing cutaneous T-cell lymphoma (CTCL) who received prior systemic therapy. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed on skin lesions in at least 50 percent of patients with CTCL. The ALCANZA trial is being conducted under a Special Protocol Assessment (SPA) agreement from the U.S. Food and Drug Administration (FDA). In addition, Takeda received European Medicines Agency (EMA) scientific advice. In 2012, the FDA granted ADCETRIS orphan drug designation for the treatment of mycosis fungoides (MF), which is the most common type of CTCL. ADCETRIS is currently not approved for the treatment of CTCL.

“We are pleased to announce the completion of patient enrollment in the phase 3 ALCANZA clinical trial evaluating ADCETRIS as a potential treatment for CD30-expressing CTCL”

Data from two investigator-sponsored phase 2 clinical trials evaluating ADCETRIS in relapsed CTCL were recently published in the Journal of Clinical Oncology (JCO) by physicians at Stanford University and the University of Texas MD Anderson Cancer Center. The results of these two clinical trials demonstrated objective response rates of 70 and 73 percent, respectively, in relapsed CTCL patients having variable levels of CD30 expression treated with ADCETRIS. This compares to objective response rates of 30 to 45 percent from published trials utilizing standard of care treatments in this disease setting. The most common adverse events in these trials were peripheral neuropathy, fatigue, nausea, skin rash, hair loss, diarrhea, muscle pain and neutropenia.

“We are pleased to announce the completion of patient enrollment in the phase 3 ALCANZA clinical trial evaluating ADCETRIS as a potential treatment for CD30-expressing CTCL,” said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “We look forward to reporting results from the ALCANZA trial in the second half of 2016 to potentially support an ADCETRIS supplemental Biologics License Application seeking a label expansion for use in this setting.”

The following highlights data summaries from the JCO publications.

Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project (Published on July 20, 2015)

The phase 2 investigator-sponsored trial enrolled CTCL patients with MF or Sézary syndrome, which are types of CTCL. Of the 32 patients enrolled in the study, 30 were evaluable for efficacy and more than half had received three or more prior systemic therapies. The primary endpoint of the trial was objective clinical response rate. The study was led by principle investigator Dr. Youn H. Kim from Stanford University School of Medicine in Stanford, CA. Key findings include:

• Twenty-one of 30 patients (70 percent) achieved an objective response across all stages of disease, including Stage IB, Stage IIB and Stage IV/SS. Overall, one patient had a complete response, 20 patients had a partial response, four patients had stable disease and five patients had progressive disease. Two patients were not evaluable for response. Of the patients who had partial responses, seven had near complete responses with over 90 percent skin improvement as measured by modified Severity-Weighted Assessment Tool (mSWAT) scores and eight were still responding to therapy.
• Responses appeared to be durable; six- and 12-month Kaplan-Meier estimates indicated continuing responses in 90 percent and 79 percent of patients, respectively.
• The most common related adverse events of any grade were peripheral neuropathy (66 percent), fatigue (47 percent), nausea (28 percent), hair loss (22 percent) and neutropenia (19 percent).
• The most common Grade 3 or 4 related adverse events were neutropenia (four patients), rash (three patients) and peripheral neuropathy (one patient).

Results of a Phase II Trial of Brentuximab Vedotin (SGN-35) for CD30+ Cutaneous T-Cell Lymphomas and Lymphoproliferative Disorders (Published on August 10, 2015)

Data were published from a phase 2 investigator-sponsored trial evaluating the use of ADCETRIS in CD30-positive CTCL patients, including lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (pcALCL) or MF. The study was conducted by Dr. Madeleine Duvic from the University of Texas MD Anderson Cancer Center in Houston, TX. Among 54 patients enrolled, 48 patients were evaluable at the time of analysis. The primary endpoint of the trial was to evaluate the safety and efficacy of ADCETRIS in CD30-positive CTCL. The key findings include:

• Thirty-five of 48 patients (73 percent) achieved an objective response, including 20 of 20 (100 percent) with LyP and/or pcALCL and 15 of 28 (54 percent) with MF. Seventeen patients (35 percent) achieved a complete response.
• The most common adverse events were peripheral neuropathy (67 percent), fatigue (35 percent), skin rash (24 percent), diarrhea (15 percent), muscle pain (17 percent), localized skin infection (15 percent), neutropenia (15 percent) and hair loss (11 percent).
• The most common Grade 3 or 4 adverse events were neutropenia (three patients), nausea (two patients), unstable angina or myocardial infarction (two patients), infection (two patients), joint pain (two patients), fatigue (one patient), deep vein thrombosis (one patient), pulmonary embolism (one patient), aminotransferase elevation (one patient) and dehydration (one patient).

ALCANZA Trial design

ALCANZA is a randomized, open-label, phase 3 trial of single agent ADCETRIS versus investigator’s choice of methotrexate or bexarotene in patients with CD30-positive CTCL, including those with pcALCL or MF. The primary endpoint of the study is overall response rate lasting at least 4 months in patients with CD30-expressing MF or pcALCL. Key secondary endpoints are complete response, progression-free survival and burden of symptoms during treatment.

For more information about the trial, please visit www.clinicaltrials.gov.

About CTCL

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 (HL) and non-Hodgkin lymphoma (NHL). Cutaneous lymphomas are a category of non-Hodgkin lymphomas that primarily involve the skin. According to the Cutaneous Lymphoma Foundation, CTCL is the most common type of cutaneous lymphoma and typically presents with red, scaly patches or thickened plaques of skin that often mimic eczema or chronic dermatitis. Progression from limited skin involvement is variable and may be accompanied by tumor formation, ulceration and exfoliation, complicated by itching and infections. Advanced stages are defined by involvement of lymph nodes, peripheral blood and internal organs. According to published literature, CD30 is expressed on skin lesions in at least 50 percent of CTCL patients.

The standard treatment for systemically pretreated CTCL includes skin-directed therapies, radiation and systemic therapies. The systemic therapies currently approved for treatment have demonstrated 30 to 45 percent objective response rates, with low complete response rates.

About ADCETRIS

ADCETRIS is being evaluated broadly in more than 30 ongoing clinical trials, including the phase 3 ALCANZA trial and two additional phase 3 studies, one in frontline classical HL and one in frontline mature T-cell lymphomas, as well as trials in many additional types of CD30-expressing malignancies, including B-cell lymphomas.

ADCETRIS 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 has received approval from the FDA for three indications: (1) regular approval for the treatment of patients with classical HL after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (2) regular approval for the treatment of classical HL patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Health Canada granted ADCETRIS approval with conditions for relapsed or refractory HL and sALCL.

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 55 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 is 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 a CD30-targeted ADC that, in collaboration with Takeda Pharmaceutical Company Limited, is commercially available in more than 55 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 in CD30-expressing malignancies. Seattle Genetics is also advancing a robust pipeline of clinical-stage programs, including SGN-CD19A, SGN-CD33A, SGN-LIV1A, SGN-CD70A, ASG-22ME, ASG-15ME and SEA-CD40. 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^® (brentuximab vedotin).

Contraindication

ADCETRIS is contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).

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.
• Anaphylaxis and infusion reactions: Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an infusion-related reaction occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy.
• Hematologic toxicities: Prolonged (=1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia 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. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.
• Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or 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.
• Increased toxicity in the presence of severe renal impairment: The frequency of =Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment compared to patients with normal renal function. Avoid the use of ADCETRIS in patients with severe renal impairment.
• Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of =Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment compared to patients with normal hepatic function. Avoid the use of ADCETRIS in patients with moderate or severe hepatic impairment.
• Hepatotoxicity: Serious cases of hepatotoxicity, including fatal outcomes, have occurred with ADCETRIS. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first dose of ADCETRIS or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may also increase the risk. Monitor liver enzymes and bilirubin. Patients experiencing new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.
• Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death has been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS therapy, with some cases occurring within 3 months of initial exposure. 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. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
• Pulmonary Toxicity: Events of noninfectious pulmonary toxicity including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, some with fatal outcomes, have been reported. Monitor patients for signs and symptoms of pulmonary toxicity, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement.
• Serious dermatologic reactions: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), including fatal outcomes, have been reported with ADCETRIS. If SJS or TEN 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.

Most Common Adverse Reactions:

ADCETRIS was studied as monotherapy in 160 patients with relapsed classical HL and sALCL in two uncontrolled single-arm 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.

ADCETRIS was studied in 329 patients with classical HL at high risk of relapse or progression post-auto-HSCT in a placebo-controlled randomized trial. The most common adverse reactions (=20%) in the ADCETRIS-treatment arm (167 patients), regardless of causality, were neutropenia, peripheral sensory neuropathy, thrombocytopenia, anemia, upper respiratory tract infection, fatigue, peripheral motor neuropathy, nausea, cough, and diarrhea.

Drug Interactions:

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

Use in Specific Populations:

MMAE exposure and adverse reactions are increased in patients with moderate or severe hepatic impairment or severe renal impairment. Avoid use.

For additional Important Safety Information, including Boxed WARNING, please see the full Prescribing Information for ADCETRIS at http://www.seattlegenetics.com/pdf/adcetris_USPI.pdf.

Forward-Looking Statements:

Certain of the statements made in this press release are forward-looking, such as those, among others, relating to the therapeutic and commercial potential of ADCETRIS, including ADCETRIS’ potential as a treatment for systemically pretreated CTCL, the anticipated timing of data from the ALCANZA trial, the anticipated benefits of Seattle Genetics’ ADCETRIS clinical development program, and the potential submission of supplemental Biologics License Application seeking a label expansion for ADCETRIS use in the ALCANZA setting. 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 risks of adverse events associated with ADCETRIS use, negative or unexpected ADCETRIS clinical trial results even after promising results in earlier company- and investigator-sponsored trials, and adverse regulatory actions affecting ADCETRIS, all of which could result in Seattle Genetics being unable to expand ADCETRIS’ labeled indications of use to the ALCANZA or any other settings. Seattle Genetics may also experience delays in the conduct of and obtaining data from the ALCANZA and its other clinical trials, in each case for a variety of reasons, including the inherent difficulty and uncertainty of pharmaceutical product development. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2015 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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