– Median Overall Survival Not Reached After 26.5 Month Median
– Data to be Presented at the 17th European
Hematology Association Annual Meeting –
BOTHELL, Wash.--(BUSINESS WIRE)--Jun. 14, 2012--
Genetics, Inc. (Nasdaq: SGEN) today announced updated survival data
from a pivotal clinical trial of single-agent ADCETRIS (brentuximab
vedotin) in patients with relapsed or refractory Hodgkin lymphoma (HL)
after autologous stem cell transplant (ASCT) showing that the median
overall survival has not been reached after a 26.5 month median
follow-up. The data will be reported during an oral presentation at the
17th European Hematology Association (EHA) Annual Meeting
being held June 14-17, 2012 in Amsterdam, Netherlands. ADCETRIS is an
antibody-drug conjugate (ADC) directed to CD30.
“Heavily pretreated Hodgkin lymphoma patients who relapse following
autologous stem cell transplant often have a poor prognosis and there is
a high unmet medical need for effective treatment options,” said Scott
Smith M.D., Ph.D., Loyola University Medical Center. “These updated
overall survival results from the pivotal trial are encouraging and
demonstrate that ADCETRIS may play an important role in the treatment of
patients with relapsed or refractory disease.”
Long-term Follow-up Results of an Ongoing Pivotal Study of
Brentuximab Vedotin in Patients with Relapsed or Refractory Hodgkin
A pivotal trial was conducted in 102 patients with relapsed or
refractory HL after ASCT. The primary endpoint was objective response
rate (ORR) per independent review. The secondary endpoints were complete
remission (CR) rate, duration of response, progression-free survival
(PFS), overall survival (OS), and safety and tolerability. At the time
of the long-term follow-up analysis, the median observation time from
first dose was 26.5 months. Data, to be presented by Dr. Smith, include:
As previously reported, the ORR was 75 percent (76 of 102 patients),
with CRs observed in 33 percent of patients (n=34).
The median OS had not been reached at the time of the analysis. The
estimated OS at 24 months was 65 percent.
The median PFS for all patients was 5.6 months. The median PFS for
patients achieving a CR was 29 months.
As previously reported, the most common (≥20 percent) adverse events
(AEs) of any grade were peripheral sensory neuropathy (47 percent),
fatigue (46 percent), nausea (42 percent), upper respiratory tract
infection (37 percent), diarrhea (36 percent), pyrexia (29 percent),
neutropenia (22 percent), vomiting (22 percent) and cough (21 percent).
Of the AEs that were reported in ≥20 percent of patients, Grade 3 or
higher events included neutropenia (20 percent), peripheral sensory
neuropathy (9 percent), fatigue (2 percent), pyrexia (2 percent) and
diarrhea (1 percent).
Patients received 1.8 milligrams per kilogram of ADCETRIS every 3 weeks
as a 30-minute outpatient intravenous infusion for up to 16 cycles.
Patients received a median of nine cycles of ADCETRIS while on trial.
The median age of patients in the pivotal trial was 31 years. Enrolled
patients had received a median of 3.5 (range 1–13) prior cancer-related
systemic therapies, excluding ASCT. Seventy-one percent of patients had
primary refractory disease, defined in the study protocol as patients
who relapsed within three months of attaining CR or failed to achieve a
CR, and 42 percent had not responded to their most recent prior therapy.
Details of the oral presentation are as follows:
Sunday, June 17; 8:30 AM – 8:45 AM Central European Summer Time (CEST)
Oral presentation in Hall 2
First author: Scott Smith M.D., Ph.D., Loyola University Medical Center
ADCETRIS (brentuximab vedotin) 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 received accelerated approval from the U.S. Food and Drug
Administration (FDA) for two indications: (1) the treatment of patients
with Hodgkin lymphoma after failure of autologous stem cell transplant
(ASCT) or after failure of at least two prior multi-agent chemotherapy
regimens in patients who are not ASCT candidates, and (2) the treatment
of patients with systemic anaplastic large cell lymphoma (sALCL) after
failure of at least one prior multi-agent chemotherapy regimen. The
indications for ADCETRIS are based on response rate. There are no data
available demonstrating improvement in patient-reported outcomes or
survival with ADCETRIS.
ADCETRIS is not approved for use outside the United States. The
marketing authorization application for ADCETRIS in relapsed or
refractory Hodgkin lymphoma and sALCL, filed by Takeda Global Research &
Development Centre (Europe), was accepted for review by the European
Medicines Agency for review in June 2011.
Seattle Genetics and Millennium are jointly developing ADCETRIS. Under
the terms of the collaboration agreement, Seattle Genetics has U.S. and
Canadian commercialization rights and the Takeda Group has rights to
commercialize ADCETRIS in the rest of the world. Seattle Genetics and
the Takeda Group are funding joint development costs for ADCETRIS on a
50:50 basis, except in Japan where the Takeda Group will be solely
responsible for development costs.
About 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. 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
generally expresses CD30.
According to the American Cancer Society, more than 8,800 cases of
Hodgkin lymphoma will be diagnosed in the United States during 2012 and
approximately 1,300 people will die from the disease. Globally, there
are more than 30,000 cases of Hodgkin lymphoma diagnosed each year.
Although front-line combination chemotherapy can result in durable
response rates, up to 30 percent of these patients relapse or are
refractory to front-line treatment and have few therapeutic options
About Seattle Genetics
Seattle Genetics is a biotechnology company focused on the development
and commercialization of monoclonal antibody-based therapies for the
treatment of cancer. The FDA granted accelerated approval of ADCETRIS in
August 2011 for two indications. ADCETRIS is being developed in
collaboration with Millennium: The Takeda Oncology Company. In addition,
Seattle Genetics has three other clinical-stage ADC programs: SGN-75,
ASG-5ME and ASG-22ME. Seattle Genetics has collaborations for its ADC
technology with a number of leading biotechnology and pharmaceutical
companies, including Abbott, Bayer, Celldex Therapeutics, Daiichi
Sankyo, Genentech, GlaxoSmithKline, Millennium, Pfizer and Progenics, as
well as ADC co-development agreements with Agensys, an affiliate of
Astellas, and Genmab. More information can be found at www.seattlegenetics.com.
U.S. Important Safety Information
Progressive multifocal leukoencephalopathy (PML): JC virus infection
resulting in PML and death can occur in patients receiving ADCETRIS.
Concomitant use of ADCETRIS and bleomycin is contraindicated due to
Warnings and Precautions:
Peripheral neuropathy: ADCETRIS treatment causes a peripheral
neuropathy that is predominantly sensory. Cases of peripheral motor
neuropathy have also been reported. ADCETRIS-induced peripheral
neuropathy is cumulative. Treating physicians should monitor patients
for symptoms of neuropathy, such as hypoesthesia, hyperesthesia,
paresthesia, discomfort, a burning sensation, neuropathic pain or
weakness and institute dose modifications accordingly.
Infusion reactions: Infusion-related reactions, including anaphylaxis,
have occurred with ADCETRIS. Monitor patients during infusion. If an
infusion reaction occurs, the infusion should be interrupted and
appropriate medical management instituted. If anaphylaxis occurs, the
infusion should be immediately and permanently discontinued and
appropriate medical management instituted.
Neutropenia: Monitor complete blood counts prior to each dose of
ADCETRIS and consider more frequent monitoring for patients with Grade
3 or 4 neutropenia. If Grade 3 or 4 neutropenia develops, manage by
dose delays, reductions or discontinuation. Prolonged (≥1 week) severe
neutropenia can occur with ADCETRIS.
Tumor lysis syndrome: Patients with rapidly proliferating tumor and
high tumor burden are at risk of tumor lysis syndrome and these
patients should be monitored closely and appropriate measures taken.
Progressive multifocal leukoencephalopathy (PML): JC virus infection
resulting in PML and death has been reported in ADCETRIS-treated
patients. In addition to ADCETRIS therapy, other possible contributory
factors include prior therapies and underlying disease that may cause
immunosuppression. Consider the diagnosis of PML in any patient
presenting with new-onset signs and symptoms of central nervous system
abnormalities. Evaluation of PML includes, but is not limited to,
consultation with a neurologist, brain MRI, and lumbar puncture or
brain biopsy. Hold ADCETRIS if PML is suspected and discontinue
ADCETRIS if PML is confirmed.
Stevens-Johnson syndrome: Stevens-Johnson syndrome has been reported
with ADCETRIS. If Stevens-Johnson syndrome occurs, discontinue
ADCETRIS and administer appropriate medical therapy.
Use in pregnancy: Fetal harm can occur. Pregnant women should be
advised of the potential hazard to the fetus.
ADCETRIS was studied as monotherapy in 160 patients in two phase 2
trials. Across both trials, the most common adverse reactions (≥20%),
regardless of causality, were neutropenia, peripheral sensory
neuropathy, fatigue, nausea, anemia, upper respiratory tract infection,
diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.
Patients who are receiving strong CYP3A4 inhibitors concomitantly with
ADCETRIS should be closely monitored for adverse reactions.
For additional important safety information, including Boxed WARNING,
please see the full U.S. prescribing information for ADCETRIS at www.seattlegenetics.com
Certain of the statements made in this press release are forward
looking, such as those, among others, relating to the therapeutic
potential of ADCETRIS and initiation of future clinical trials. 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 inability to show sufficient activity in future
clinical trials and the risk of adverse events as ADCETRIS advances in
clinical trials. In addition, data from our clinical trials, including
our pivotal trials which were the basis for FDA accelerated approval,
may not necessarily be indicative of subsequent clinical trial results.
More information about the risks and uncertainties faced by Seattle
Genetics is contained in the company’s 10-Q for the quarter ended March
31, 2012 filed with the Securities and Exchange Commission. Seattle
Genetics disclaims any intention or obligation to update or revise any
forward-looking statements, whether as a result of new information,
future events or otherwise.
Source: Seattle Genetics, Inc.
Peggy Pinkston, 425-527-4160