|Seattle Genetics Receives FDA Breakthrough Therapy Designation for ADCETRIS® (Brentuximab Vedotin) in Frontline Advanced Hodgkin Lymphoma|
-Designation Based on Positive Phase 3 ECHELON-1 Trial Evaluating
ADCETRIS in Frontline Advanced Hodgkin Lymphoma; Data will be Presented
-Submission of Supplemental Biologics License Application for ADCETRIS in Frontline Advanced Hodgkin Lymphoma Planned Before the End of 2017-
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 phase 3 ECHELON-1 study that supports the Breakthrough Therapy
Designation for ADCETRIS in combination with chemotherapy showed
superior activity versus the standard of care chemotherapy regimen in
the treatment of frontline advanced classical Hodgkin lymphoma
This Breakthrough Therapy Designation was based on data from the phase 3 ECHELON-1 clinical trial. The ECHELON-1 study evaluated a combination of ADCETRIS plus AVD (Adriamycin, vinblastine, dacarbazine) compared to a recognized standard of care chemotherapy regimen 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+AVD in the ECHELON-1 trial was consistent with that known for the single-agent components of the regimen.
ECHELON-1 Phase 3 Clinical Trial Design
The randomized, open-label, phase 3 trial is investigating ADCETRIS plus
AVD versus ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) 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
Please see Important Safety Information at the end of this press release.
About Classical Hodgkin Lymphoma
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. Classical Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. The Reed-Sternberg cell expresses CD30.
ADCETRIS is being evaluated broadly in more than 70 clinical trials,
including four phase 3 studies: the ECHELON-1 trial in frontline
classical Hodgkin lymphoma from which positive topline results were
recently reported, the ongoing ECHELON-2 trial in frontline mature
T-cell lymphomas, the completed ALCANZA trial in cutaneous T-cell
lymphoma that supported the supplemental BLA with a Prescription Drug
User Fee Act (PDUFA) target action date of
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-positive tumor cells.
ADCETRIS for intravenous injection has received approval from the
ADCETRIS was granted conditional marketing authorization by the
ADCETRIS has received marketing authorization by regulatory authorities in 67 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information below.
ADCETRIS (brentuximab vedotin) U.S. Important Safety Information
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
Relapsed classical HL and relapsed sALCL: neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.
Classical HL post-auto-HSCT Consolidation: neutropenia, peripheral sensory neuropathy, thrombocytopenia, anemia, upper respiratory tract infection, fatigue, peripheral motor neuropathy, nausea, cough, and diarrhea.
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, 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 for
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) as the foundation of care
for CD30-expressing lymphomas, anticipated publication of data from
ECHELON-1 and plans for submission for supplemental regulatory approval
to and obtaining regulatory approval from the