BOTHELL, Wash.--(BUSINESS WIRE)--Jan. 13, 2012--
Seattle Genetics, Inc. (Nasdaq: SGEN) today announced updates to the
U.S. Prescribing Information (PI) for ADCETRIS™ (brentuximab vedotin).
The revised PI will include the following updated information:
A boxed warning related to the risk that JC virus infection resulting
in progressive multifocal leukoencephalopathy (PML) and death can
occur in patients receiving ADCETRIS.
A discussion in the PML warning and precaution provision regarding
other possible contributing factors to PML such as other prior
therapies and underlying disease, symptoms to be aware of and
suggested methodologies for diagnosis of PML.
A contraindication warning of the concomitant use of ADCETRIS and
bleomycin due to pulmonary toxicity.
ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30 that was
granted accelerated approval by the U.S. Food and Drug Administration
(FDA) in August 2011 for two indications: (1) the treatment of patients
with Hodgkin lymphoma (HL) 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.
“Our first priority is patient safety. By developing these agreed upon
label updates with the FDA regarding PML and the contraindication with
bleomycin, we aim to heighten awareness among healthcare professionals
in order to most safely treat their patients with ADCETRIS. Although PML
in lymphoma patients can be caused by factors such as underlying disease
and prior therapies that affect the immune system, a contributory role
of ADCETRIS cannot be excluded,” said Thomas C. Reynolds, M.D., Ph.D.,
Chief Medical Officer of Seattle Genetics. “The contraindication for the
concomitant use of ADCETRIS and bleomycin is based on data suggesting an
increased risk of pulmonary toxicity relative to ABVD alone that was
identified in our phase I clinical trial in patients with newly
diagnosed advanced Hodgkin lymphoma. We are confident that these label
changes will help guide appropriate patient care while on treatment with
PML is associated with a weakened immune system that can occur in
patients with diseases such as lymphoma, leukemia and other hematologic
malignancies. According to published literature, the risk of PML in
persons with hematologic malignancies is estimated to be 0.07%, or
approximately one in 1,400 (1). More than 2,000 patients worldwide have
received treatment with ADCETRIS to date.
PML was described in the original PI for ADCETRIS based on a single case
reported in a patient who had received four chemotherapy regimens prior
to receiving ADCETRIS. Following the occurrence of a second case of PML,
Seattle Genetics began working in conjunction with the FDA to add a
boxed warning in order to heighten awareness of the potential risk of
PML. There has also been a third suspected, but unconfirmed, case of PML
reported in a heavily-pretreated patient receiving ADCETRIS.
In addition, based on data from a phase I clinical trial of ADCETRIS in
combination with ABVD (Adriamycin, bleomycin, vinblastine and
dacarbazine) for the treatment of newly diagnosed Hodgkin lymphoma
patients, a contraindication for concomitant use of bleomycin and
ADCETRIS will be added to the PI. This is based on data demonstrating
that 40 percent of patients (10 out of 25) in the ADCETRIS plus ABVD
cohorts of the trial had an event of pulmonary toxicity, compared to an
overall rate of pulmonary toxicity with bleomycin-based regimens
reported in published literature of 10 to 25 percent (2,3). To date, no
pulmonary toxicity events have been observed in the ADCETRIS plus AVD
cohorts of the trial. ADCETRIS is not approved for the front-line
treatment of Hodgkin lymphoma.
When finalized, the updated PI will be posted at www.seattlegenetics.com.
PML is a rare, progressive, demyelinating disease of the central nervous
system that often leads to death or severe disability. PML is caused by
reactivation of the John Cunningham (JC) virus. JC virus resides in
latent form in 40-80 percent of healthy adults. Reactivation of the
latent infection is associated with immunocompromised conditions and may
occur months following discontinuation of immunosuppressive therapy. PML
has been reported in patients with Hodgkin lymphoma, HIV-positive
patients, immunosuppressed cancer patients, transplantation patients and
patients with autoimmune disease. There are no known interventions that
can reliably prevent or adequately treat PML.
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.
Seattle Genetics and Millennium: The Takeda Oncology Company 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 is solely responsible for development costs.
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.
Important Safety Information
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.
Stevens-Johnson syndrome: Stevens-Johnson syndrome has been reported
with ADCETRIS. If Stevens-Johnson syndrome occurs, discontinue
ADCETRIS and administer appropriate medical therapy.
Progressive multifocal leukoencephalopathy (PML): A fatal case of PML
has been reported in a patient who received four chemotherapy regimens
prior to receiving ADCETRIS.
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, 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 continued patient
treatment with ADCETRIS. 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 risks
related to Seattle Genetics’ ability to demonstrate to the medical
community the safety and efficacy of ADCETRIS and its potential
advantages over any side effects compared to existing therapeutics and
products currently in clinical development, and risks related to the
FDA’s post-approval requirements for ADCETRIS, including the risk that
results from Seattle Genetics’ required post-approval studies may fail
to verify the clinical benefit of ADCETRIS in its approved indications.
More information about the risks and uncertainties faced by Seattle
Genetics is contained in Seattle Genetics’ quarterly report on Form 10-Q
for the quarter ended September 30, 2011, 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.
Carson, KR, et.al. Progressive multifocal leukoencephalopathy after
rituximab therapy in HIV-negative patients: a report of 57 cases
from the Research on Adverse Drug Events and Reports project. 2009.
Blood 11: 4834-4840.
Duggan DB, et.al. Randomized comparison of ABVD and MOPP/ABV hybrid
for the treatment of advanced Hodgkin’s disease: report of an
intergroup trial. 2003. J Clin Oncol 21: 607-14.
Hoskin PJ, et.al. Randomized comparison of the Stanford V regimen
and ABVD in the treatment of advanced Hodgkin’s Lymphoma: United
Kingdom National Cancer Research Institute Lymphoma Group Study
ISRCTN 64141244. 2009. J Clin Oncol 27: 5390-6.
Source: Seattle Genetics, Inc.
Seattle Genetics, Inc.
Peggy Pinkston, 425-527-4160