On January 22, 2018 Seattle Genetics, Inc. (Nasdaq: SGEN) reported that its collaborator, Takeda Pharmaceutical Company Limited, announced that the European Commission has extended the current conditional marketing authorization for ADCETRIS (brentuximab vedotin) to include the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy (Press release, Seattle Genetics, JAN 22, 2018, View Source;p=RssLanding&cat=news&id=2327637 [SID1234523420]). ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed on the surface of Hodgkin lymphoma cells and several types of non-Hodgkin lymphoma, including CTCL. The decision follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) on November 9, 2017.
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"CTCL is a debilitating and disfiguring disease with few effective and durable treatment options," said Clay Siegall, Ph.D., President and Chief Executive Officer at Seattle Genetics. "The approval of ADCETRIS for use in the European Union in CD30-positive CTCL patients represents a meaningful advance for patients with CTCL. We are pleased that our partner Takeda is able to make this therapeutic option available to patients in Europe. Since ADCETRIS was first approved by the FDA in 2011, Seattle Genetics and Takeda have made significant progress in our goal to establish ADCETRIS as the foundation of care for CD30-expressing lymphomas, and we are working together on our next milestone of securing FDA approval and European Union marketing authorization for ADCETRIS’ use as a treatment for frontline advanced Hodgkin lymphoma."
The marketing authorization for ADCETRIS is valid in 28 countries of the European Union (EU), Norway, Liechtenstein and Iceland. It is based on positive results from a phase 3 trial called ALCANZA that were presented at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2016, published online in the Lancet in June 2017, and recently updated in a poster presentation at the 59th ASH (Free ASH Whitepaper) annual meeting in December 2017. The trial achieved 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. The ORR4 was 56.3 percent in the ADCETRIS arm compared to 12.5 percent in the control arm (p-value <0.001). The key secondary endpoints specified in the protocol, including complete response rate, progression-free survival and reduction in skin symptom burden as measured by the Skindex-29 questionnaire, were all highly statistically significant in favor of the ADCETRIS arm. The safety profile associated with ADCETRIS from the ALCANZA trial was generally consistent with the existing prescribing information. The most common adverse events of any grade include: anemia, peripheral sensory neuropathy, nausea, diarrhea, fatigue and neutropenia.
For further details about the European Commission decision, please visit the European Medicines Agency website: www.ema.europa.eu/ema.
In November 2017, the U.S. Food and Drug Administration (FDA) approved ADCETRIS for the treatment of adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy based on the results of the phase 3 ALCANZA clinical trial. Together, pcALCL and CD30-expressing MF comprise approximately 70 percent of CTCL diagnoses and the majority of patients who require systemic therapy. ADCETRIS is currently not approved as a frontline therapy for Hodgkin lymphoma.
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. 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.
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 received conditional marketing authorization from the European Commission for four 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, (2) the treatment of adult patients with relapsed or refractory sALCL, (3) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, and (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.
ADCETRIS has received marketing authorization by regulatory authorities in 70 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.