Seattle Genetics Receives FDA Orphan Drug Designation for ADCETRIS® (Brentuximab Vedotin) in Mycosis Fungoides
-Designation Supports Regulatory Strategy for ADCETRIS in CTCL, including Ongoing Phase III ALCANZA Trial-
-Investigator Data on ADCETRIS in CTCL to be Presented at Upcoming ASH Annual Meeting-
BOTHELL, Wash.--(BUSINESS WIRE)-- Seattle Genetics, Inc. (NAS: SGEN) announced today that ADCETRIS (brentuximab vedotin) has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA) for the treatment of mycosis fungoides (MF). MF is the most common type of cutaneous T-cell lymphoma (CTCL). Seattle Genetics and its ADCETRIS collaborator, Millennium: The Takeda Oncology Company, are conducting the ALCANZA trial, a phase III clinical trial of ADCETRIS for patients with CD30-positive relapsed CTCL, including MF. ADCETRIS is not approved for the treatment of CTCL.
"This orphan drug designation is a part of our ADCETRIS regulatory strategy, designed to complement the Special Protocol Assessment for the ongoing ALCANZA study," said Clay B. Siegall, President and Chief Executive Officer of Seattle Genetics. "The encouraging data from investigator-sponsored trials of ADCETRIS in CTCL, which will be presented at ASH, provide further support for our activities in this patient population."
FDA orphan drug designation is intended to encourage companies to develop therapies for the treatment of diseases that affect fewer than 200,000 individuals in the United States. This designation provides Seattle Genetics with the opportunity for seven years of marketing exclusivity, grant funding to defray costs of clinical trial expenses, tax credits for clinical research expenses and potential waiver of the FDA's application user fee.
The ALCANZA trial is a randomized phase III clinical trial of ADCETRIS for relapsed CD30-positive CTCL patients. The trial is assessing ADCETRIS versus investigator's choice of methotrexate or bexarotene in patients with CD30-positive CTCL, including those with primary cutaneous anaplastic large cell lymphoma (pcALCL) or MF. The primary endpoint of the study is overall response rate lasting at least 4 months. Approximately 124 patients will be enrolled in the pivotal trial. The ALCANZA trial is being conducted under a Special Protocol Assessment agreement from the FDA. The study also received European Medicines Agency scientific advice. For more information about the ALCANZA trial, visit www.clinicaltrials.gov.
At the 54th American Society of Hematology (ASH) Annual Meeting and Exposition being held December 8-11, 2012 in Atlanta, GA, data from two investigator-sponsored trials of ADCETRIS in CTCL will be reported:
Brentuximab vedotin demonstrates significant clinical activity in relapsed or refractory mycosis fungoides with variable CD30 expression (Abstract #797)
Oral presentation on Monday, December 10; 7:15 p.m. Eastern Time (ET) in Rooms B304-B305
First author: Dr. Michael Krathen, Stanford University, Stanford, CA
Results of a phase II trial of brentuximab vedotin (SGN-35) for CD30-positive cutaneous T-cell lymphomas and lymphoproliferative disorders (Abstract #3688)
Poster presentation on Monday, December 10; 6:00 p.m. to 8:00 p.m. ET in Hall B1-B2
First author: Dr. Madeleine Duvic, The University of Texas MD Anderson Cancer Center, Houston, TX
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 was granted accelerated approval by the FDA in August 2011 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 was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) the treatment of patients with Hodgkin lymphoma after failure of 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 sALCL after failure of at least one prior multi-agent chemotherapy regimen. See important safety information below.
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 is solely responsible for development costs.
About Cutaneous T-Cell Lymphoma
Mycosis fungoides is the most common subtype of CTCL. CTCLs constitute a group of non-Hodgkin lymphomas (NHLs) and are cancers of the T lymphocytes (a type of white blood cell) that mainly affect the skin but can also involve the blood, lymph nodes and/or internal organs in patients with advanced disease. According to the Cutaneous Lymphoma Foundation, CTCL is the most common type of cutaneous lymphoma and typically presents with red, scaly patches or thickened plaques of skin that often mimic eczema or chronic dermatitis. Progression from limited skin involvement is variable and may be accompanied by tumor formation, ulceration and exfoliation, complicated by itching and infections. Advanced stages are defined by involvement of lymph nodes, peripheral blood and internal organs. According to published literature, up to 50 percent of CTCL patients' lesions express CD30.
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, Agensys (an affiliate of Astellas), Bayer, Celldex Therapeutics, Daiichi Sankyo, Genentech, GlaxoSmithKline, Millennium, Pfizer and Progenics, as well as ADC co-development agreements with Agensys 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 pulmonary toxicity.
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.
Certain of the statements made in this press release are forward looking, such as those, among others, relating to our belief that there exists clinical evidence for pursuing the approval of ADCETRIS for CTCL. 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 that data resulting from the ALCANZA trial with ADCETRIS will not support approvals in any of the studied indications. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company's 10-Q for the quarter ended September 30, 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.
KEYWORDS: United States North America Washington
The article Seattle Genetics Receives FDA Orphan Drug Designation for ADCETRIS® (Brentuximab Vedotin) in Mycosis Fungoides originally appeared on Fool.com.
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