|Seattle Genetics Announces Updates to ADCETRIS™ Prescribing Information|
ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30 that was
granted accelerated approval by the
“Our first priority is patient safety. By developing these agreed upon
label updates with the
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,
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.
Important Safety Information
Warnings and Precautions:
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.
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, Inc.