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FDA Grants Breakthrough Therapy Designation to ADCETRIS® (Brentuximab Vedotin) for Frontline Peripheral T-Cell Lymphomas
November 15, 2018 at 8:00 AM EST
-Designation Based on Positive Phase 3 ECHELON-2 Trial Evaluating ADCETRIS in Frontline CD30-Expressing Peripheral T-Cell Lymphomas; Data to be Presented at Upcoming American Society of Hematology Annual Meeting in December-
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.
“Data from the ECHELON-2 phase 3 trial of ADCETRIS in combination with
chemotherapy showed superior progression-free survival and overall
survival versus the standard of care chemotherapy regimen, CHOP, in the
treatment of frontline CD30-expressing peripheral T-cell lymphomas,”
This Breakthrough Therapy Designation was based on data from the phase 3 ECHELON-2 clinical trial evaluating the combination of ADCETRIS plus CHP versus the control arm, 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) of ADCETRIS in combination with CHP versus CHOP 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.
ECHELON-2 Phase 3 Clinical Trial Design
The randomized, double-blind, placebo-controlled phase 3 trial is
investigating ADCETRIS plus CHP (cyclophosphamide, doxorubicin,
prednisone) versus CHOP (cyclophosphamide, doxorubicin, vincristine,
prednisone) as frontline therapy in patients with CD30-expressing
peripheral T-cell lymphoma, also known as mature T-cell lymphoma. The
primary endpoint is progression-free survival (PFS) per Independent
Review Facility assessment, with events defined as progression, death,
or receipt of chemotherapy for residual or progressive disease.
Secondary endpoints include PFS in patients with systemic anaplastic
large cell lymphoma (sALCL), complete remission rate, overall survival
and objective response rate, in addition to safety. The multi-center
trial was conducted at sites across
Please see Important Safety Information, including Boxed Warning, at the end of this press release.
About T-Cell Lymphomas
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
About ADCETRIS (brentuximab vedotin)
ADCETRIS is being evaluated broadly in more than 70 clinical trials in CD30-expressing lymphomas. These include the recently completed phase 3 ECHELON-2 trial in frontline peripheral T-cell lymphomas (also known as mature T-cell lymphoma), the completed phase 3 ECHELON-1 trial in previously untreated Hodgkin lymphoma, the completed phase 3 ALCANZA trial in cutaneous T-cell lymphoma, and the ongoing CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma.
ADCETRIS is an 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
ADCETRIS received conditional marketing authorization from the
ADCETRIS has received marketing authorization by regulatory authorities in 72 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See select important safety information, including Boxed Warning, below.
ADCETRIS (brentuximab vedotin) Important Safety Information
BOXED WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML):
JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.
ADCETRIS concomitant with bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).
Warnings and Precautions
Most Common (≥20%) Adverse Reactions: Neutropenia, anemia,peripheral sensory neuropathy, nausea, fatigue, constipation, diarrhea, vomiting, and pyrexia.
Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to monomethyl auristatin E (MMAE).
Use in Specific Populations
Moderate or severe hepatic impairment or severe renal impairment: MMAE exposure and adverse reactions are increased. Avoid use.
Advise males with female sexual partners of reproductive potential to use effective contraception during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.
Advise patients to report pregnancy immediately and avoid breastfeeding while receiving ADCETRIS.
Forward Looking Statements
Certain of the statements made in this press release are forward
looking, such as those, among others, relating to the therapeutic
potential of ADCETRIS (brentuximab vedotin) for patients with previously
untreated systemic anaplastic large cell lymphoma or other
CD30-expressing peripheral T-cell lymphomas (PTCL), including
angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in
combination with CHP (cyclophosphamide, doxorubicin, and prednisone) and
anticipated presentation of data from the ECHELON-2 clinical trial at
ASH in 2018. Actual results or developments may differ materially from
those projected or implied in these forward-looking statements. Factors
that may cause such a difference include the possibility that we will be
required to amend our submission for marketing approval or that such
submission will be refused or delayed. More information about the risks
and uncertainties faced by