Seattle Genetics, Inc. announced Tuesday that the U.S. Food and Drug Administration (FDA) has accepted for filing a supplemental Biologics License Application (sBLA) for Adcetris (brentuximab vedotin) in combination with chemotherapy for the frontline treatment of patients with advanced classical Hodgkin lymphoma.
The FDA granted priority review for the application, and the Prescription Drug User Fee Act (PDUFA) target action date is May 1, 2018.
The submission of the supplemental BLA is based on positive results from a Phase 3 clinical trial called ECHELON-1 that was designed to determine if Adcetris in combination with chemotherapy could extend modified progression-free survival (modified PFS) in previously untreated advanced classical Hodgkin lymphoma patients.
Adcetris is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical Hodgkin lymphoma. Adcetris is being evaluated globally as the foundation of care for CD30-expressing lymphomas in more than 70 corporate- and investigator-sponsored clinical trials. Adcetris is currently not approved as a frontline therapy for Hodgkin lymphoma.
In October 2017, the FDA granted Adcetris Breakthrough Therapy Designation based on the ECHELON-1 study results. 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 in one or more clinically significant endpoints.
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 includes bleomycin), in frontline advanced classical Hodgkin lymphoma.
The positive results from the phase 3 ECHELON-1 trial were featured in the Plenary Scientific Session of the 59th American Society of Hematology (ASH) Annual Meeting with simultaneous publication in the New England Journal of Medicine in December 2017. Results from the ECHELON-1 trial in 1,334 Hodgkin lymphoma patients included:
- The trial achieved its primary endpoint with the combination of Adcetris plus AVD resulting in a statistically significant improvement in modified PFS versus the control arm of ABVD as assessed by an Independent Review Facility (IRF) (p-value=0.035). This corresponds to a 23 percent reduction in the risk of progression, death or need for additional anticancer therapy. Per IRF assessment, the two-year modified PFS rate for patients in the Adcetris plus AVD arm was 82.1 percent compared to 77.2 percent in the control arm.
- The investigator assessment of modified PFS also demonstrated a statistically significant advantage for Adcetris plus AVD versus the control arm of ABVD (p-value <0.01).
- All secondary endpoints, including interim analysis of overall survival, trended in favor of the Adcetris plus AVD arm.
- 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 randomized, open-label, phase 3 trial is investigating Adcetris plus AVD versus ABVD as frontline therapy in patients with advanced classical Hodgkin lymphoma.
(Source: Seattle Genetics, Inc.)
Filed Under: Drug Discovery