Takeda Pharmaceutical Company Limited, a global, R&D-driven pharmaceutical company, 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 current conditional approval of Adcetris (brentuximab vedotin) and recommended its approval for the treatment of adult patients with CD30+ Hodgkin lymphoma at increased risk of relapse or progression following autologous stem cell transplantation (ASCT).
The CHMP positive opinion for Adcetris will now be reviewed by the European Commission (EC). If the CHMP recommendation is formally adopted by the EC, which has the authority to approve medicines for the European Union (EU), Adcetris will be approved for marketing of this indication in the 28 member states of the EU, Norway Liechtenstein and Iceland.
This opinion is based on the results of the phase 3 AETHERA study. The AETHERA trial met its primary endpoint with Adcetris (plus best supportive care) treatment resulting in a statistically significant improvement in progression-free survival (PFS) versus placebo (plus best supportive care) as assessed by an independent central review committee (hazard ratio=0.57; p-value=0.001), which equates to a 75 percent improvement in PFS. PFS was assessed after a minimum of two years post initiation of treatment for all study patients. An updated analysis conducted after three years of follow up showed sustained PFS improvement (per Independent Review Facility; HR=0.58; 95 per cent CI (0.41,0.81). A pre-specified interim analysis of overall survival showed no statistically significant difference between the treatment arms. The safety profile of Adcetris in the AETHERA trial was generally consistent with the existing prescribing information.
Adcetris (brentuximab vedotin) 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 proprietary technology by Seattle Genetics. 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 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 the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). In January 2016, the European Commission approved a Type II variation to include data on the retreatment of adult patients with Hodgkin lymphoma or sALCL who previously responded to Adcetris and who later relapse. Adcetris has received marketing authorization by regulatory authorities in more than 60 countries.
Adcetris is being evaluated broadly in more than 45 ongoing clinical trials, including the phase 3 ALCANZA trial in CD30+ cutaneous T cell lymphoma (CTCL) and two additional phase 3 studies, one in frontline classical Hodgkin lymphoma (ECHELON-1) and one in frontline CD30+ mature T-cell lymphomas (ECHELON-2), as well as trials in many additional types of CD30-expressing malignancies.
Seattle Genetics and Takeda are jointly developing Adcetris. Under the terms of the collaboration agreement, Seattle Genetics has US 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.
