Seattle Genetics Submits Supplemental BLA for Adcetris in T-Cell Lymphomas

November 5, 2018
  • PTCL accounts for approximately 10 percent of non-Hodgkin lymphoma cases in the U.S. and Europe
  • It may account for as much as 24 percent in parts of Asia.


Seattle Genetics, Inc. (Nasdaq:SGEN) announced on 11/5/18 that it has submitted a supplemental Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) based on data from the phase 3 ECHELON-2 trial evaluating Adcetris (brentuximab vedotin) in combination with chemotherapy for the frontline treatment of patients with CD30-expressing peripheral T-cell lymphoma (PTCL). The positive topline results of the phase 3 ECHELON-2 clinical trial were announced in October 2018 and full data will be presented at the upcoming American Society of Hematology (ASH) Annual Meeting, December 1-4, 2018 in San Diego, Calif. Adcetris is an antibody-drug conjugate (ADC) directed to CD30, which is expressed on the surface of several types of PTCL. Adcetris is currently not approved for the frontline treatment of PTCL.

“CD30 is expressed in several subtypes of peripheral T-cell lymphoma, an aggressive type of non-Hodgkin lymphoma, and the current standard of care for frontline treatment consisting of a multi-agent chemotherapy regimen called CHOP has not changed in several decades,” said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “Results from the ECHELON-2 trial demonstrated a statistically significant and clinically meaningful improvement in progression-free survival and importantly, overall survival, in patients with previously untreated CD30-expressing PTCL who were treated with Adcetris in combination with CHP chemotherapy over standard of care CHOP chemotherapy. We believe these superior results over standard of care represent a significant advance for patients with CD30-expressing PTCL and for the medical community, and we look forward to working with the FDA during the review process of this application to bring this potential new treatment regimen to patients as quickly as possible.”

The phase 3 ECHELON-2 clinical trial evaluated the combination of Adcetris plus CHP (cyclophosphamide, doxorubicin, prednisone) compared to a recognized standard of care chemotherapy regimen, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), in previously untreated CD30-expressing PTCL. The ECHELON-2 study met its primary endpoint demonstrating a statistically significant improvement in progression-free survival (PFS) as assessed by an Independent Review Facility (IRF; hazard ratio=0.71; p-value=0.0110). The Adcetris plus CHP arm also demonstrated superior overall survival (OS), a key secondary endpoint, compared to CHOP (hazard ratio=0.66; p-value=0.0244). All other key secondary endpoints, including PFS in patients with systemic anaplastic large cell lymphoma (sALCL), complete remission rate and objective response rate were statistically significant in favor of the Adcetris plus CHP arm. The safety profile of Adcetris plus CHP in the ECHELON-2 trial was comparable to CHOP and consistent with the established safety profile of Adcetris in combination with chemotherapy.

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. There are more than 60 subtypes of non-Hodgkin lymphomas which are broadly divided into two major groups: B-cell lymphomas, which develop from abnormal B-lymphocytes, and T-cell lymphomas, which develop from abnormal T-lymphocytes. There are many different forms of T-cell lymphomas, some of which are extremely rare. T-cell lymphomas can be aggressive (fast-growing) or indolent (slow-growing). PTCL accounts for approximately 10 percent of non-Hodgkin lymphoma cases in the U.S. and Europe and may be as high as 24 percent in parts of Asia.

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-expressing tumor cells.

Adcetris injection for intravenous infusion has received FDA approval for five indications in adult patients with: (1) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with chemotherapy, (2) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (3) 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, (4) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (5) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

In recent third quarter results, Adcetris, sales were up 60% for the quarter, but fell short of management's guidance.


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