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Seattle Genetics Submits Supplemental Biologics License Application to FDA for ADCETRIS® (Brentuximab Vedotin) in Frontline Advanced Hodgkin Lymphoma
November 2, 2017 at 8:00 AM EDT
-Submission Based on Positive Results from the Phase 3 ECHELON-1 Clinical Trial-
-ECHELON-1 Data will be Featured in the ASH Annual Meeting Plenary
Scientific Session on
-FDA Recently Granted Breakthrough Therapy Designation to ADCETRIS in Combination with Chemotherapy for Frontline Treatment of Advanced Classical 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
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
ADCETRIS was recently granted Breakthrough Therapy Designation by the
ECHELON-1 Phase 3 Clinical Trial Design
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
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.
According to the
ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30 and 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 top-line results were recently reported and
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 for intravenous injection has received
ADCETRIS was granted conditional marketing authorization by the
ADCETRIS has received marketing authorization by regulatory authorities in 68 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information below.
ADCETRIS (brentuximab vedotin) U.S. 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: peripheral sensory neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, 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, and for at least 6 months after the final dose of ADCETRIS treatment.
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 anticipated regulatory approval from the