Euro Commission okays ‘ADCETRIS’
Positive opinion given on drugs
CAMBRIDGE, Mass/OSAKA, Japan, Feb 12, (Business Wire): Takeda Pharmaceutical Company Limited today announced that the European Commission (EC) 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. ADCETRIS is an antibodydrug conjugate (ADC) directed at CD30, a defining marker of Hodgkin lymphoma. The decision follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) on Dec 13, 2018.
“The decision by the European Commission is a welcomed advancement for patients with previously untreated Stage IV Hodgkin lymphoma – a population that has not been offered a new treatment option in decades,” said Anna Sureda, MD, PhD, Head of the Hematology Department and Hematopoietic Stem Cell Transplant Programme, Institut Català d’Oncologia – Hospital Duran i Reynals. “Patients with Stage IV disease carry a higher risk of progression following their first therapy and experience poorer outcomes as a result. The approval of this regimen may help address this unmet need by providing European physicians and their patients with a new option that showed significant benefit compared to ABVD along with a safety profile consistent with when ADCETRIS is used as a single agent.”
Navarro
Safety
“We are pleased that the European Commission has approved ADCETRIS in combination with AVD, which has the potential to represent an important milestone for patients and serves as a testament to Takeda’s longstanding commitment to the Hodgkin lymphoma community,” said Jesús Gómez-Navarro, MD, Vice-President, Head of Oncology Clinical Research and Development, Takeda. “The ECHELON-1 clinical trial demonstrated that the addition of ADCETRIS and the removal of bleomycin from the standard ABVD regimen yielded both efficacy and safety benefits in patients. We look forward to making this therapy available for appropriate European patients with Hodgkin lymphoma.”
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.
The trial achieved its primary endpoint resulting in a statistically significant improvement in modified progression-free survival (PFS) versus the control arm (Hazard ratio [HR] 0.77; p-value=0.035), which corresponds to a 23 percent 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 percent 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.
Term
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 percent of previously untreated Hodgkin lymphoma patients progress following their first therapy depending on the stage of the disease. Only 50 percent of patients with relapsed or refractory Hodgkin lymphoma achieve long-term remission with highdose chemotherapy and an autologous stem cell transplant (ASCT), a historically used treatment regimen, highlighting the need for successful treatments for previously untreated patients.
ADCETRIS is an antibody-drug conjugate (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 six indications in adult patients with: (1) previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone, (2) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine, (3) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (4) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (5) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (6) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30expressing mycosis fungoides (MF) who have received prior systemic therapy.