Seattle Genetics Announces FDA Approval of ADCETRIS® (Brentuximab Vedotin) for Primary Cutaneous Anaplastic Large Cell Lymphoma (pcALCL) and CD30-Expressing Mycosis Fungoides (MF)

-MF and pcALCL Represent the Most Common Subtypes of Cutaneous T-Cell Lymphoma (CTCL)-

-FDA Approval Based on Clinical Trial Results from the Phase 3 ALCANZA and Phase 2 Investigator-Sponsored Studies in CTCL-

-Label Expansion Represents Fourth Indication for ADCETRIS in the U.S.-

BOTHELL, WA, USA I November 9, 2017 I Seattle Genetics, Inc. (Nasdaq: SGEN) announced today that the U.S. Food and Drug Administration (FDA) has approved ADCETRIS (brentuximab vedotin) for the treatment of adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) and CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy. Primary cutaneous ALCL and MF are the most common subtypes of cutaneous T-cell lymphoma (CTCL). The approval is based on data from the phase 3 ALCANZA trial and two phase 2 investigator-sponsored trials. The phase 3 ALCANZA study was designed to compare ADCETRIS monotherapy administered every three weeks versus physician’s choice of representative standard of care options, methotrexate or bexarotene. The trial met its primary endpoint with the ADCETRIS treatment arm demonstrating a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4) versus the control arm as assessed by an independent review facility. ORR4 was 56.3 percent (95% CI: 44.1, 68.4) in the ADCETRIS arm compared to 12.5 percent (95% CI: 4.4, 20.6) in the control arm (p-value <0.001). The most common adverse reactions (≥ 20 percent) were: anemia, peripheral sensory neuropathy, nausea, diarrhea, fatigue and neutropenia.

This is the fourth FDA-approved indication for ADCETRIS, which also has: (1) regular approval for treatment of classical Hodgkin lymphoma (cHL) patients who fail autologous hematopoietic stem cell transplantation (auto-HSCT) or who fail at least two prior multi-agent chemotherapy regimens and are not auto-HSCT candidates, (2) regular approval for the treatment of patients with cHL at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for treatment of systemic anaplastic large cell lymphoma (sALCL) patients who fail at least one prior multi-agent chemotherapy regimen. Accelerated approval in the sALCL indication is based on overall response rate, and continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

In November 2016, the FDA granted ADCETRIS Breakthrough Therapy Designation (BTD) for the treatment of patients with pcALCL and CD30-expressing MF who require systemic therapy and have received one prior systemic therapy. The FDA also granted Priority Review for the supplemental Biologics License Application (BLA), and the Prescription Drug User Fee Act (PDUFA) target action date was December 16, 2017.

“Cutaneous T-cell lymphoma is a blood cancer of the skin with no known cure and few new treatment options. It is a disfiguring disease in dire need of more effective and durable treatment options to help keep this debilitating and painful disease at bay,” said Susan Thornton, cutaneous lymphoma patient and chief executive officer of the Cutaneous Lymphoma Foundation (CLF). “As both a patient and representative of the cutaneous lymphoma community, we welcome the FDA approval of ADCETRIS as a new treatment option for the most common subtypes of cutaneous T-cell lymphoma in patients who require systemic therapy and we look forward to sharing this important milestone with patients and physicians.”

“Our phase 3 ALCANZA clinical trial evaluating ADCETRIS in patients with primary cutaneous anaplastic large cell lymphoma and mycosis fungoides, which are the most common types of cutaneous T-cell lymphoma, demonstrated superior efficacy with durable responses for long-term disease management when compared to standard of care treatment options methotrexate and bexarotene,” said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “These data, along with data from investigator-sponsored clinical trials, led to the FDA approval of ADCETRIS as a treatment for patients with pcALCL or CD30-expressing MF, which represent the most common subtypes of CTCL. This FDA approval, which was granted more than a month in advance of the PDUFA date, represents a significant milestone for the lymphoma community. Our goal is to establish ADCETRIS as the foundation of care in CD30-expressing lymphomas and this approval represents our fourth FDA-approved indication.”

The FDA approval is based primarily on positive results from a phase 3 trial called ALCANZA that were presented at the 58th American Society of Hematology (ASH) annual meeting in December 2016 and published online in the Lancet in June 2017. Results from the ALCANZA trial in 128 pcALCL and CD30-expressing MF patients requiring systemic therapy included:

  • The trial achieved its primary endpoint with the ADCETRIS treatment arm demonstrating a highly statistically significant improvement in the rate of ORR4 versus the control arm as assessed by an independent review facility. ORR4, as assessed by Global Response Score, was 56.3 percent in the ADCETRIS arm compared to 12.5 percent in the control arm (p-value <0.001).
  • Key secondary endpoints specified in the protocol, including objective response rate, complete response rate and progression-free survival, were all highly statistically significant in favor of the ADCETRIS arm.
    • The objective response rate in the ADCETRIS arm was 67.2 percent (95% CI: 55.7, 78.7) compared to 20.3 percent (95% CI: 10.5, 30.2) in the control arm.
    • The CR rate in the ADCETRIS arm was 15.6 percent (95% CI: 7.8, 26.9) compared to 1.6 percent (95% CI: 0, 8.4) in the control arm (p-value = 0.0066).
  • The median PFS in the ADCETRIS arm was 16.7 months (95% CI: 14.9, 22.8) compared to 3.5 months (95% CI: 2.4, 4.6) in the control arm (HR 0.270; 95% CI, 0.169, 0.430; p-value <0.001).
  • The safety profile associated with ADCETRIS from the ALCANZA trial was generally consistent with the existing prescribing information. The most common adverse events occurring in 20 percent or more of patients of any grade include: anemia, peripheral sensory neuropathy, nausea, diarrhea, fatigue and neutropenia.

Additional data from two investigator-sponsored phase 2 trials evaluating ADCETRIS in 73 MF patients were also incorporated into the supplemental BLA representing a broader spectrum of CD30-expression levels than that of the ALCANZA 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 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 an antibody-drug conjugate (ADC) directed to CD30 and is being evaluated broadly in more than 70 clinical trials, including three phase 3 studies: the ECHELON-1 trial in frontline classical Hodgkin lymphoma from which positive top-line results were recently reported, the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, and the recently initiated 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 patients with pcALCL and CD30-expressing MF and 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 68 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.

SOURCE: Seattle Genetics

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