On June 7, 2017 Takeda Pharmaceutical Company Limited (TSE:4502) and Seattle Genetics, Inc. (NASDAQ: SGEN) reported that data from the randomized Phase 3 ALCANZA clinical trial evaluating ADCETRIS (brentuximab vedotin) in patients with cutaneous T-cell lymphoma (CTCL) were published in the journal Lancet (Press release, Seattle Genetics, JUN 7, 2017, View Source [SID1234519463]). Data were previously presented in an oral session at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2016. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30 which is expressed on CTCL lesions in approximately 50 percent of patients with the disease. ADCETRIS is currently not approved for the treatment of CTCL. Schedule your 30 min Free 1stOncology Demo! "Today’s publication of the positive results of the ALCANZA trial is another milestone for our brentuximab vedotin clinical program. We plan to submit the data to regulatory bodies around the world, and if approved, ADCETRIS would be a potential new treatment option for patients with CD30-positive CTCL, a rare, debilitating and often difficult to treat form of cancer," said Dirk Huebner, M.D., Executive Medical Director, Oncology Therapeutic Area Unit, Takeda Pharmaceutical Company. "We are encouraged by the data we’ve seen from our robust ongoing clinical investigation program of ADCETRIS in CD30-positive lymphomas, and are committed to bringing this important therapy to patients."
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"The ALCANZA study is the first randomized Phase 3 clinical trial to evaluate a novel agent versus standard of care in CTCL, an incurable and disfiguring disease with few treatment options that achieve durable responses," said Bob Lechleider, M.D., Senior Vice President, Clinical Development of Seattle Genetics. "The data from the ALCANZA trial provide compelling evidence that CTCL patients treated with ADCETRIS had superior outcomes across the primary and all secondary endpoints assessed in the study compared to patients in the control arm who were treated with a standard of care agent. These data demonstrate the potential of ADCETRIS to change the treatment landscape of CTCL."
ALCANZA is a randomized, open-label Phase 3 study designed to evaluate single-agent ADCETRIS versus a control arm of investigator’s choice of the standard of care therapies methotrexate or bexarotene, in patients with CD30-positive CTCL. The manuscript highlights data from the trial which 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. 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 <0.0001). Key secondary endpoints specified in the protocol, including complete response rate, progression-free survival and reduction in the burden of symptoms during treatment (Skindex-29), 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: peripheral neuropathy, nausea, diarrhea, fatigue, vomiting, alopecia, pruritis, pyrexia, decreased appetite and hypertriglyceridemia.
Based on the study results, Takeda plans to begin to submit data from the ALCANZA trial to regulatory agencies in its territories in 2017. The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to ADCETRIS for the treatment of the most common subtypes of CTCL, mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL). Seattle Genetics plans to submit these data as part of a supplemental Biologics License Application to the FDA in mid-2017. The ALCANZA trial received a Special Protocol Assessment (SPA) agreement from the FDA and scientific advice from the European Medicines Agency (EMA).
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. 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 published literature, CD30 is expressed on CTCL lesions in approximately 50 percent of patients with the disease.
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 70 ongoing clinical trials, including three Phase 3 studies, the ongoing ECHELON-1 trial in frontline classical Hodgkin lymphoma and the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, as well as the completed ALCANZA trial in cutaneous T-cell lymphoma for which a supplemental BLA is planned in mid-2017.
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-positive 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 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, (2) regular approval for the treatment of classical Hodgkin lymphoma 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 Hodgkin lymphoma 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 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 67 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.