On July 14, the FDA’s Oncologic Drugs Advisory Committee (ODAC) will review Seattle Genetics' two Biologics License Applications (BLAs) for brentuximab vedotin (Adcetris). ODAC plans to review the BLA for the treatment of relapsed or refractory Hodgkin lymphoma during the morning session and the BLA for the treatment of relapsed or refractory systemic anaplastic large cell lymphoma (ALCL) during the afternoon session. The results from the meeting will probably be released sometime Thursday afternoon. The briefing documents for the meeting, likely to be released on Tuesday, will provide the initial dose of volatility for the stock.
Brentuximab vedotin is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of Hodgkin lymphoma and ALCL. The product candidate has been granted orphan drug designation by the FDA and European Medicines Agency for the treatment of Hodgkin lymphoma and ALCL.
The two BLAs are currently under priority 6-month review by the FDA with a PDUFA date of August 30. FDA administratively separated the original BLA submission and will act individually on the application for each indication.
Seattle Genetics is developing brentuximab vedotin in collaboration with Millennium: The Takeda Oncology Group. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and the Takeda Group (OTCPK:TKPHF) has rights to commercialize brentuximab vedotin in the rest of the world. Seattle Genetics and the Takeda Group are funding joint development costs for brentuximab vedotin on a 50:50 basis, except in Japan where Takeda will be solely responsible for development costs.
Adcetris For Lymphoma BLA
Lymphoma is a general term for a group of cancers that originate in the lymphatic system. According to the American Cancer Society, approximately 8,500 cases of Hodgkin lymphoma were diagnosed in the United States during 2010 and more than 1,300 people were expected to die from the disease. Although front-line combination chemotherapy can result in durable response rates, up to 30% of these patients relapse or are refractory to front-line treatment and have few therapeutic options beyond autologous stem cell transplant (ASCT).
After releasing the top-line results for the pivotal Phase II trial for the product candidate for lymphoma last fall, Seattle Genetics presented the full results in December at the American Society of Hematology meeting. The single-arm pivotal trial assessed efficacy and safety of single-agent brentuximab vedotin in relapsed or refractory, ASCT Hodgkin lymphoma patients. Patients received 1.8 milligrams per kilogram of brentuximab vedotin every three weeks for up to 16 total doses. The primary endpoint of the trial was objective response rate as assessed by an independent central review.
The median age of patients on the pivotal trial was 31 years. Enrolled patients had received a median of 3.5 prior chemotherapy regimens. Seventy one percent of patients were primary refractory, defined as patients who failed to achieve a complete remission to front-line chemotherapy or had relapsed within three months of receiving front-line chemotherapy. Forty two percent of patients were refractory to their most recent prior therapy, and all patients had progressed following prior ASCT.
Seventy five percent of patients achieved an objective response as assessed by an independent central review, including 34% complete remissions and 40% partial remissions. The median duration of response was 29 weeks by independent central review and 47 weeks by investigator assessment. Twenty two percent of patients had stable disease, 3% had progressive disease and one patient was not evaluable for response. A high level of concordance was observed between independently reviewed and investigator-assessed response. Tumor reductions were achieved in 94% of patients. Progression-free survival (PFS) among all patients was 25 weeks by independent review and 39 weeks by investigator assessment. PFS among patients achieving a complete remission has not yet been reached. Median overall survival had not yet been reached.
Brentuximab vedotin treatment was associated with manageable adverse events, with the most common being peripheral sensory neuropathy, fatigue, nausea, upper respiratory tract infection and diarrhea. The most common Grade 3 or higher adverse events were neutropenia, peripheral sensory neuropathy, thrombocytopenia and anemia.
The pivotal trial was conducted under a Special Protocol Assessment with the FDA and was discussed with the EMA during the process of obtaining EU Centralized Scientific Advice on the brentuximab vedotin development program.
Adcetris For ALCL BLA
ALCL is an aggressive type of T-cell non-Hodgkin lymphoma that highly expresses CD30. In the United States, approximately 2,000 systemic ALCL patients are diagnosed annually. Although front-line combination chemotherapy can result in durable remissions, approximately 50% of ALCL patients relapse or are refractory to front-line treatment and have few therapeutic options.
The key clinical trial for this BLA is the Phase II trial for which results were released late last year. The single-arm trial assessed efficacy and safety of single-agent brentuximab vedotin in relapsed or refractory systemic ALCL patients. Patients received 1.8 milligrams per kilogram of brentuximab vedotin every three weeks for up to 16 total doses. The primary endpoint of the trial was overall objective response rate as assessed by an independent central review
The median age of patients in the phase II trial was 52 years. Enrolled patients had received a median of two prior chemotherapy regimens. Sixty two percent of patients were primary refractory, defined as patients who did not achieve a complete remission to front-line chemotherapy or who relapsed within three months of receiving front-line chemotherapy. Seventy two percent of patients were anaplastic lymphoma kinase (ALK) negative, generally suggesting a poor prognosis. Twenty four percent of patients did not respond to any prior treatment, and 26% had failed prior autologous stem cell transplant.
Eighty six percent of patients achieved an objective response as assessed by an independent central review, including 53% complete remissions and 33% partial remissions. An additional 3% of patients had stable disease, 5% had progressive disease and 5% were not evaluable or were histologically ineligible. A high level of concordance was observed between independently reviewed and investigator-assessed response. Median duration of response and median progression-free survival had not yet been reached. Tumor reductions were achieved in 97% of patients. B-symptoms resolved in 82% of patients in whom such symptoms were present at baseline (14 out of 17). Thirty one percent of patients remained on treatment.
As in the Lymphoma trial, the Brentuximab vedotin treatment was associated with manageable adverse events.
About The Company
Seattle Genetics is a clinical-stage biotechnology company focused on the development and commercialization of monoclonal antibody-based therapies for the treatment of cancer and autoimmune disease. In addition to brentuximab vedotin, Seattle Genetics has four other clinical-stage programs: SGN-75, ASG-5ME, dacetuzumab (SGN-40) and SGN-70. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies. At the end of Q1, the company had nearly $456 million in cash. The company had operating expenses of just over $45 million in Q1.
Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.