The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for the extension of the present provisional approval of Takeda Pharmaceutical’s Adcetris (brentuximab vedotin), and recommended that the drug should be approved to treat CD30+ Hodgkin lymphoma in patients at increased risk of relapse or disease progression after autologous stem cell transplantation (ASCT).
Hodgkin lymphoma (HL) is distinguished from other types of lymphoma (a group of cancers that originates in the lymphatic system) by the presence of one type of cell, called the Reed-Sternberg cell, which expresses the cell membrane protein CD30. The current “gold standard” treatment for chemosensitive relapsed/refractory HL is high-dose salvage chemotherapy plus ASCT. This method is estimated to treat approximately 50 percent of HL cases.
Prescribing Adcetris after ASCT is a new treatment approach, and based on the positive data from AETHERA, a randomized double-blind, and placebo-controlled Phase 3 study. The trial is evaluating overall survival, and the safety and tolerability of Adcetris, in patients with relapsed or refractory HL at risk of progression following ASCT.
“While ASCT is the standard of care following failure of frontline chemotherapy in Hodgkin lymphoma, we know that many patients will unfortunately see their disease return. Early eradication of residual disease through treatment with ADCETRIS has the highest chance of preventing the disease from returning in these patients,” said Dirk Huebner, MD, executive medical director, Oncology Therapeutic Area Unit, Takeda Pharmaceutical, in a press release. “This opinion, in addition to the recent five year overall survival data in relapsed or refractory Hodgkin lymphoma, further establishes the role of ADCETRIS in improving outcomes for patients. We look forward to the European Commission’s authorization of this new indication and bringing this medicine to physicians and patients in the European Union.”
The European Commission (EC) will now review CHMP’s opinion, and if the recommendation is adopted the therapy will be marketed for this indication in the 28 member states of the European Union as well as in Iceland, Norway, and Liechtenstein.
CHMP’s opinion is based on the results of the AETHERA trial, which evaluated if early treatment with Adcetris could prevent disease progression in HL patients who had either relapsed or showed no response to prior treatment but were in remission or had stable, non-progressing disease after salvage chemotherapy prior to transplant. The trial met its primary endpoint, with Adcetris (and best supportive care) resulting in an improvement in progression-free survival (PFS) compared to placebo (and best supportive care), as evaluated by an independent review board.
In the AETHERA trial, 327 patients were randomized to receive either brentuximab vedotin (BV, Adcetris) post-ASCT or a placebo. Results revealed that after two years, patients who received BV treatment had a 20 percent improvement without disease progression compared to those that received a placebo (PFS rate of 65% vs. 45%). An updated analysis, conducted after a follow-up of three years, demonstrated a sustained improvement in PFS, and the results from an interim analysis of overall survival showed no differences between the treatment arms. The safety profile of Adcetris was generally consistent in the trial with the existing prescribing information.