Seattle Genetics Highlights Updated Analyses from Phase III ALCANZA Clinical Trial of ADCETRIS (Brentuximab Vedotin) in CD30-Expressing Cutaneous T-Cell Lymphoma at ASH Annual Meeting

ATLANTA--(BUSINESS WIRE)-- Seattle Genetics, Inc. (Nasdaq: SGEN) today highlighted updated results from the phase 3 ALCANZA clinical trial evaluating ADCETRIS (brentuximab vedotin) in CD30-expressing cutaneous T-cell lymphoma (CTCL) at the 59^th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in Atlanta, Georgia, December 9-12, 2017. The presentation highlighted longer-term durability data from the phase 3 ALCANZA clinical trial of single-agent ADCETRIS for the treatment of patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF). Together, these comprise approximately 70 percent of CTCL diagnoses and the majority of patients who require systemic therapy.

“The updated analyses from the phase 3 ALCANZA clinical trial presented at this year’s ASH annual meeting are based on longer-term follow-up by investigators. Since the initial presentation at the ASH Annual Meeting in 2016, the ALCANZA results continue to show superior clinical efficacy of ADCETRIS over standard-of-care therapies in patients with CD30-expressing CTCL,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “The updated analyses demonstrate that the primary and secondary endpoints per investigator are better than previously reported by independent review facility assessment. CTCL is a debilitating and disfiguring disease. With the recent FDA approval of ADCETRIS for use in two common subtypes based on the ALCANZA results, we are now able to provide patients with a clinically meaningful therapeutic option in the approved settings. This is a significant milestone for the lymphoma community and for our goal to make ADCETRIS available to as many patients as possible with CD30-expressing lymphomas.”

Updated Analyses of the International, Open-Label, Randomized, Phase 3 ALCANZA Study: Longer-term Evidence for Superiority of Brentuximab Vedotin Versus Methotrexate or Bexarotene for CD30-Positive Cutaneous T-Cell Lymphoma (Abstract #1509, poster presentation on Saturday, December 9, 2017)

ALCANZA was a randomized, open-label phase 3 study designed to evaluate single-agent ADCETRIS versus a control arm of investigator’s choice of standard of care therapies, methotrexate or bexarotene, in patients with CD30-expressing pcALCL or MF. Patients with pcALCL must have received at least one prior systemic or radiation therapy and patients with MF must have received at least one prior systemic therapy. A total of 131 patients were randomized with 128 patients in the intent-to-treat population. Sixty-four patients were assigned to the ADCETRIS arm and 64 patients were assigned to the control arm. Patients received ADCETRIS or investigator’s choice of methotrexate or bexarotene for up to approximately one year.

Data from longer-term patient follow-up per investigator assessment in the phase 3 ALCANZA trial after a median observation time of 33.9 months from the first dose of ADCETRIS versus physician’s choice include:

• The trial achieved its primary endpoint of demonstrating a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4) in the ADCETRIS arm versus the control arm. The ORR4 per investigator assessment was 60.9 percent in the ADCETRIS arm compared to 7.8 percent in the control arm (p-value <0.001).
• The key secondary endpoints per investigator, including complete response (CR) rate, progression-free survival (PFS) and reduction in the burden of symptoms during treatment (per Skindex-29 questionnaire), continued to be all highly statistically significant in favor of the ADCETRIS arm.
  • The median PFS per investigator in the ADCETRIS arm was 15.8 months compared to 3.6 months in the control arm (HR 0.373; 95% CI, 0.245-0.569; p-value <0.001).
  • The CR rate in the ADCETRIS arm was 18.8 percent compared to zero percent in the control arm (p-value <0.001).
  • Patient-reported quality of life assessed by the Skindex-29 questionnaire showed significantly greater symptom reduction for patients in the ADCETRIS arm versus the control arm (mean maximum change of -28.08 vs -8.62; p-value <0.001).
• At time of the analyses, 47 patients (73 percent) in the ADCETRIS arm and 48 patients (75 percent) in the physician’s choice arm had received one or more subsequent skin-directed or systemic therapy. The median time to next treatment in the ADCETRIS arm was significantly longer at 14.2 months compared with the physician’s choice arm at 6.1 months (p-value <0.001). In the ADCETRIS versus physician’s choice arms, the probability of patients not requiring subsequent skin-directed or systemic therapy was greater at one year (65.5 percent vs. 15.3 percent) and two years (24.6 percent vs. 4.4 percent).
• Peripheral neuropathy events were observed in 44 of 66 patients (67 percent) in the ADCETRIS arm and four of 62 patients (six percent) in the physician’s choice arm. In the ADCETRIS arm, 86 percent of patients reported resolution or improvement in peripheral neuropathy events, with 59 percent reporting resolution of all events after a median of 30 weeks and 27 percent reporting some improvement after a median of 13 weeks. Eighteen patients had ongoing peripheral neuropathy events, including 15 patients with Grade 1 and three patients with Grade 2.

In November 2017, the U.S. Food and Drug Administration (FDA) approved ADCETRIS for the treatment of adult patients with pcALCL or CD30-expressing MF who have received prior systemic therapy based on the results of the phase 3 ALCANZA clinical trial.

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 and non-Hodgkin lymphoma. Cutaneous lymphomas are a category of non-Hodgkin lymphoma 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. The most common subtypes of CTCL include mycosis fungoides and primary cutaneous anaplastic large cell lymphoma. Progression from limited skin involvement may be accompanied by skin 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 the American Cancer Society and the Leukemia and Lymphoma Society, CTCL represents approximately four percent of non-Hodgkin lymphoma, which is about 2,800 patients. Not all newly diagnosed patients require systemic therapy. The standard treatment for CTCL patients includes skin-directed therapies, radiation and systemic therapies. Prior to the FDA approval of ADCETRIS, systemic therapies approved for treatment demonstrated 30 to 45 percent objective response rates, with low complete response rates and low durability as demonstrated by a median time to next systemic treatment of 3.9 months for chemotherapy and 4.5 months for histone deacetylase inhibitors.

About ADCETRIS

ADCETRIS is being evaluated broadly in more than 70 clinical trials, including three phase 3 studies: the completed ECHELON-1 trial in frontline classical Hodgkin lymphoma that supported the recent FDA Breakthrough Therapy Designation and submission of the supplemental Biologics License Application (BLA) for use in this setting, the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, and the ongoing CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma.

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 injection for intravenous infusion has received FDA approval for four indications: (1) regular approval for adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy, (2) regular approval for the treatment of patients with classical Hodgkin lymphoma 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, (3) regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (4) 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 Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-ASCT consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.

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 Hodgkin lymphoma 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. The European Commission extended the current conditional marketing authorization of ADCETRIS and approved ADCETRIS for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT.

ADCETRIS has received marketing authorization by regulatory authorities in 69 countries for relapsed or refractory Hodgkin lymphoma and sALCL. 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 an innovative biotechnology company dedicated to improving the lives of people with cancer through novel antibody-based therapies. The company’s industry-leading antibody-drug conjugate (ADC) technology harnesses the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. Seattle Genetics commercializes ADCETRIS^® (brentuximab vedotin) for the treatment of several types of CD30-expressing lymphomas. The company is also advancing a robust pipeline of novel therapies for solid tumors and blood-related cancers designed to address significant unmet medical needs and improve treatment outcomes for patients. More information can be found at www.seattlegenetics.com and follow @SeattleGenetics on Twitter.

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 ADCETRIS-treated patients.

Contraindication

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

Warnings and Precautions

• Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Institute dose modifications accordingly.
• Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.
• 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 ADCETRIS dose. 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 ADCETRIS-treated patients. Closely monitor patients during treatment for 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 use 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 use in patients with moderate or severe hepatic impairment.
• Hepatotoxicity: Serious cases, including fatal outcomes, have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.
• 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. Other possible contributory factors other than ADCETRIS include prior therapies and underlying disease that may cause immunosuppression. Consider PML diagnosis in patients 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: Noninfectious pulmonary toxicity events including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, some with fatal outcomes, have been reported. Monitor patients for signs and symptoms, 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.
• Gastrointestinal (GI) complications: Acute pancreatitis, including fatal outcomes, has been reported in ADCETRIS-treated patients. Other fatal and serious GI complications, including perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus have been reported in ADCETRIS-treated patients. Lymphoma with preexisting GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, perform a prompt diagnostic evaluation and treat appropriately.
• Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus, and to avoid pregnancy during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.

Most Common (≥20%) Adverse Reactions: peripheral sensory neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, and pyrexia.

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

Moderate or severe hepatic impairment or severe renal impairment: MMAE exposure and adverse reactions are increased. Avoid use.

Advise males with female sexual partners of reproductive potential to use effective contraception during, and for at least 6 months after the final dose of ADCETRIS treatment.

Advise patients to report pregnancy immediately and avoid breastfeeding while receiving ADCETRIS.

For additional Important Safety Information, including BOXED WARNING, please see the full Prescribing Information for ADCETRIS at www.seattlegenetics.com or www.ADCETRIS.com.

Forward-Looking Statement:

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 for use in the treatment of patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF), and Seattle Genetics’ goal to make ADCETRIS available to as many patients as possible with CD30-expressing lymphomas. 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, a lack of use of ADCETRIS in the approved settings for a variety of reasons including market conditions, reimbursement, expense, and competition, and adverse regulatory actions, and the failure to expand ADCETRIS’ labeled indications. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption “Risk Factors” included in the company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2017 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.

View source version on businesswire.com: http://www.businesswire.com/news/home/20171209005001/en/