FDA gave Seattle Genetics’ Adcetris (brentuximab vedotin) the go-ahead to treat Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL). The drug was approved under the FDA's accelerated approval program and is the first new sanctioned treatment for HL since 1977 and the first specifically indicated to treat ALCL.
Adcetris is an antibody-drug conjugate (ADC) developed on Seattle Genetics’ technology. It comprises an anti-CD30 mAb attached by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE). The linker system is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.
Adcetris is to be used in patients with HL whose disease has progressed after autologous stem cell transplant or after two prior chemotherapy treatments for those who cannot receive a transplant. Adcetris may also be used in patients with ALCL whose disease has progressed after one prior chemotherapy treatment.
"Early clinical data suggests that patients who received Adcetris for Hodgkin lymphoma and systemic anaplastic lymphoma experienced a significant response to the therapy," says Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research.
The effectiveness of Adcetris in patients with HL was evaluated in a one single-arm trial involving 102 patients. The study's primary endpoint was objective response rate, the percentage of patients who experienced complete or partial cancer shrinkage or disappearance after treatment. Data demonstrated that 73% achieved an objective response, including 32% with complete remissions and 40% with partial remissions. The median duration of objective response was 6.7 months.
The effectiveness of Adcetris in patients with systemic ALCL was also evaluated in a single-arm trial, which was conducted in 58 patients. The study showed that 86% achieved an objective response, including 57% with complete remissions and 29% with partial remissions. The median duration of objective response was 12.6 months.
Seattle Genetics expects to launch the drug next week. The firm will continue to evaluate the treatment for post-transplant HL relapse prevention (Phase III), retreatment of Hodgkin lymphoma (Phase II), front-line HL (Phase I), and front-line systemic ALCL (Phase I).
The company has additional ADCs in preclinical and Phase I development, including four in-house programs in renal cell carcinoma, non-Hodgkin lymphoma, pancreatic cancer, prostate cancer, and CD19+ hematologic malignancies. It is also involved in 11 clinical-stage ADC programs that are partnered with other companies.