11 February 2019 - - The European Commission extended the current marketing authorization of Adcetris (brentuximab vedotin) to include treatment of adult patients with previously untreated CD30+ Stage IV Hodgkin lymphoma in combination with AVD (Adriamycin, vinblastine and dacarbazine), Takeda Pharmaceutical company Ltd. (TSX: 4502) (NYSE: TAK) said.

Adcetris is an antibody-drug conjugate directed at CD30, a defining marker of Hodgkin lymphoma.

The decision follows a positive opinion from the Committee for Medicinal Products for Human Use on December 13, 2018.

The approval is based on the results of the randomized, open-label, two-arm, multi-center Phase 3 ECHELON-1 study designed to compare Adcetris plus AVD to ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine) as a therapy in adult patients with previously untreated Hodgkin lymphoma.

According to the company, the trial achieved its primary endpoint resulting in a statistically significant improvement in modified progression-free survival versus the control arm (Hazard ratio [HR] 0.77; p-value=0.035), which corresponds to a 23% reduction in the risk of progression, death or need for additional anticancer therapy.

Key subgroup analyses showed a larger effect in patients with Stage IV Hodgkin lymphoma in the Adcetris plus AVD arm versus the control arm (modified PFS; HR 0.71; p-value = 0.023).

The safety profile of Adcetris plus AVD in the ECHELON-1 trial was generally consistent with that known for the single-agent components of the regimen.

The most common clinically relevant adverse events of any grade that occurred in at least 15% of patients in the Adcetris plus AVD and ABVD arms were: neutropenia, constipation, vomiting, fatigue, peripheral sensory neuropathy, diarrhea, pyrexia, peripheral neuropathy, abdominal pain and stomatitis.

In both the Adcetris plus AVD and ABVD arms, the most common Grade 3 or 4 events were neutropenia, febrile neutropenia and neutrophil count decrease.

This decision by the European Commission means that Adcetris in combination with AVD is now approved for marketing of this indication in the 28 member states of the European Union and applicable in Norway, Liechtenstein and Iceland.

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.

Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell.

The Reed-Sternberg cell expresses CD30.

According to the Lymphoma Coalition, approximately 67,000 people worldwide are diagnosed with Hodgkin lymphoma each year and more than 25,000 people die each year from this cancer.

Up to 30% of previously untreated Hodgkin lymphoma patients progress following their first therapy depending on the stage of the disease.

Only 50% of patients with relapsed or refractory Hodgkin lymphoma achieve long-term remission with high-dose chemotherapy and an autologous stem cell transplant, a historically used treatment regimen, highlighting the need for successful treatments for previously untreated patients.

Adcetris is an antibody-drug conjugate comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E, 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 internalisation into CD30-positive tumor cells.