– Opinion based on positive Phase 3 ALCANZA study results which demonstrated a highly statistically significant improvement in rate of objective response lasting at least four months, median progression-free survival and overall response rate, and decrease in symptom burden in ADCETRIS arm

CAMBRIDGE, MA, USA and OSAKA, Japan I November 14, 2017 I Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for the extension of the marketing authorization of ADCETRIS® (brentuximab vedotin) and recommended its approval for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy. ADCETRIS is an antibody-drug conjugate (ADC) directed at CD30 which is expressed on skin lesions in approximately 50 percent of patients with CTCL. ADCETRIS is currently not approved for the treatment of CTCL.

“This opinion represents a crucial first step forward for European patients living with CTCL, a debilitating disease that can have a significant impact on their quality of life,” said Julia Scarisbrick, M.D., Department of Dermatology, University Hospital Birmingham, Birmingham, UK. “The results of the ALCANZA trial demonstrate impressive efficacy along with a manageable safety profile when compared with methotrexate and bexarotene, commonly used therapies. If approved in Europe, ADCETRIS would offer a novel treatment option for CD30-expressing CTCL patients.”

“Today’s positive CHMP opinion is an important milestone for the CTCL community, and further reinforces the role ADCETRIS may have in improving outcomes for patients with CD30-positive malignancies” said Jesus Gomez Navarro, M.D., Vice President, Head of Oncology Clinical Research and Development, Takeda. “For patients with CTCL, there is a significant need for additional treatment options that increase the opportunity to achieve durable responses. We look forward to the European Commission’s review of the CHMP positive opinion of this new indication and the possibility to bring ADCETRIS to appropriate CTCL patients in the European Union.”

The CHMP positive opinion for ADCETRIS will now be reviewed by the European Commission (EC), which has the authority to approve medicines for use in the 28 countries of the European Union (EU), Norway, Liechtenstein and Iceland.

The positive CHMP opinion is based on the results of the randomized, open-label Phase 3 ALCANZA 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-positive CTCL. The trial achieved its primary endpoint and the ADCETRIS treatment arm demonstrated a highly statistically significant improvement in the overall response rate lasting at least four months (ORR4) versus the control arm as assessed by an independent review facility (p-value <0.0001). The ORR4 was 56.3 percent in the ADCETRIS arm compared to 12.5 percent in the control arm. The key secondary endpoints specified in the protocol, including complete response rate, progression-free survival and reduction in the burden of symptoms during treatment, as measured by the Skindex-29 questionnaire1, 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. In the ADCETRIS arm, the most common grade 3 or 4 events were peripheral sensory neuropathy (no grade 4 events), fatigue, diarrhea, nausea, vomiting and pruritis. In the control arm, the most common grade 3 or 4 events were hypertriglyceridemia, pruritis, fatigue and pyrexia. 

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 mimics 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 CTCL includes skin-directed therapies, radiation and systemic therapies or a combination of these. 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 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 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 more than 65 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information below.

ADCETRIS is being evaluated broadly in more than 70 clinical trials, including a Phase 3 study in frontline Hodgkin lymphoma (ECHELON-1) and another Phase 3 study in frontline CD30-positive peripheral T-cell lymphomas (ECHELON-2), as well as trials in many additional types of CD30-positive malignancies.

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 Takeda Pharmaceutical Company

Takeda Pharmaceutical Company Limited is a global, research and development-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its R&D efforts on oncology, gastroenterology and central nervous system therapeutic areas plus vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. New innovative products, especially in oncology and gastroenterology, as well as our presence in Emerging Markets, fuel the growth of Takeda. More than 30,000 Takeda employees are committed to improving quality of life for patients, working with our partners in health care in more than 70 countries. For more information, visit http://www.takeda.com/news.

Additional information about Takeda is available through its corporate website, www.takeda.com, and additional information about Takeda Oncology, the brand for the global oncology business unit of Takeda Pharmaceutical Company Limited, is available through its website, www.takedaoncology.com.

1The well-established Skindex-29 is a three-dimensional, dermatology-specific health-related quality of life (HRQL) questionnaire. Twenty-nine items are combined to form three domains: symptoms, emotions, and functioning. The domain scores and an overall score are expressed on a 100-point scale, with higher scores indicating lower levels of quality of life. https://doi.org/10.1038/jid.2009.404

SOURCE: Takeda Pharmaceutical Co