Seattle Genetics seeks US FDA approval for Adcetris in frontline advanced Hodgkin lymphoma

“There have been no new treatment advances for frontline Hodgkin lymphoma in more than 40 years. Up to 30 percent of the patients diagnosed with advanced disease will experience disease progression after frontline treatment with the current standard of care chemotherapy regimen, representing a significant unmet need to improve the treatment outcome of these patients who are often young adults,” said Clay Siegall, Ph.D., president and chief executive officer of Seattle Genetics. “Results from the ECHELON-1 study demonstrated superior activity of an Adcetris-containing regimen over standard of care, and resulted in FDA Breakthrough Therapy Designation for Adcetris in combination with chemotherapy for frontline advanced classical Hodgkin lymphoma. We believe these data represent a significant advance for the patient and physician community and look forward to working with the FDA to complete the review of this new treatment regimen as quickly as possible.”

The ECHELON-1 study evaluated a combination of Adcetris plus AVD (Adriamycin, vinblastine, dacarbazine) compared to a recognized standard of care chemotherapy regimen, ABVD (which also includes bleomycin), in previously untreated advanced classical Hodgkin lymphoma. The ECHELON-1 study met its primary endpoint of a statistically significant improvement in modified progression-free survival (PFS) of the Adcetris containing regimen versus the control arm as assessed by an Independent Review Facility (hazard ratio=0.770; p-value=0.035). The two-year modified PFS rate for patients in the Adcetris arm was 82.1 percent compared to 77.2 percent in the control arm. Interim analysis of overall survival, the key secondary endpoint, also trended in favor of the Adcetris plus AVD arm. The safety profile of Adcetris plus AVD in the ECHELON-1 trial was consistent with that known for the single-agent components of the regimen. Full data from the ECHELON-1 study will be presented in the Plenary Scientific Session at the American Society of Hematology (ASH) Annual Meeting on Sunday, December 10, 2017 from 2:00 – 4:00 p.m. ET in Atlanta, Georgia.

Adcetris was recently granted Breakthrough Therapy Designation by the FDA based on data from the phase 3 ECHELON-1 clinical trial. The FDA’s Breakthrough Therapy Designation is intended to expedite the development and review of promising drug candidates for serious or life-threatening conditions. It is based upon clinical evidence of substantial improvement over existing therapies on one or more clinically significant endpoints.

The randomized, open-label, phase 3 trial is investigating Adcetris plus AVD versus ABVD as frontline therapy in patients with advanced classical Hodgkin lymphoma. The primary endpoint is modified PFS per Independent Review Facility assessment using the Revised Response Criteria for Malignant Lymphoma. Modified PFS is defined as the time to progression, death or receipt of additional anticancer therapy for patients who are not in complete response after completion of frontline therapy per Independent Review Facility. This endpoint was chosen as it provides a clearer picture of the efficacy of frontline chemotherapy and eliminates the confounding impact of salvage and consolidation chemotherapies and radiotherapy. Secondary endpoints include overall survival, complete remission and safety. The multi-center trial was conducted in North America, Europe, South America, Australia, Asia and Africa. The study enrolled 1,334 patients who had a histologically-confirmed diagnosis of Stage III or IV classical Hodgkin lymphoma and had not been previously treated with systemic chemotherapy or radiotherapy. The ECHELON-1 trial is being conducted under a Special Protocol Assessment (SPA) agreement from the FDA and the trial also received European Medicines Agency (EMA) scientific advice.

Seattle genetics seeks us fda approval,adcetris, frontline advanced hodgkin lymphoma