Seattle Genetics, Inc. has submitted a supplemental Biologics License Application (sBLA) to the US Food and Drug Administration (FDA) supporting the use of Adcetris (brentuximab vedotin) for retreatment and extended duration beyond 16 cycles of therapy in relapsed Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL). Adcetris is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of HL and sALCL, that was granted accelerated approval by the FDA in August 2011 for relapsed HL and relapsed sALCL.

“The sBLA submission includes data demonstrating Adcetris activity in managing HL and sALCL when used in the retreatment setting, as well as beyond the 16 cycles described in our current label, while retaining a manageable safety profile,” said Clay B Siegall, Ph.D., president and chief executive officer of Seattle Genetics. “Our goal is to broaden the Adcetris US labeling claims to provide both patients and physicians the opportunity to incorporate Adcetris into additional HL and sALCL treatment settings. The sBLA submission includes data that support these uses and we look forward to the regulatory outcome.”

The sBLA is based on results from a phase II clinical trial with two treatment arms. One arm evaluated retreatment with ADCETRIS in patients who previously responded to treatment with ADCETRIS, then discontinued treatment and subsequently had disease progression or relapse. The other arm allowed treatment extension and evaluated prolonged treatment with Adcetris beyond 16 cycles of therapy. The sBLA submission includes updated data sets from this phase II trial. Preliminary data from this trial were previously reported at the 2011 American Society of Hematology (ASH) Annual Meeting and at the 2012 American Society of Clinical Oncology (ASCO) Annual meeting.

At the 2012 ASCO Annual Meeting, retreatment data from the phase II trial were reported from 23 patients, including one patient who was treated twice. Patients had received a median of four prior systemic therapies, including Adcetris. Of 23 evaluable patients, 70 per cent (16 of 23) achieved an objective response after retreatment with Adcetris, including nine complete remissions and seven partial remissions. Median duration of retreatment objective response was 8.8 months. Among retreated HL patients, nine of 16 (56 per cent) achieved an objective response. Among retreated sALCL patients, seven of eight (88 per cent) achieved an objective response. The most common adverse events were peripheral neuropathy (46 per cent), nausea (42 per cent), fatigue (38 per cent), diarrhoea (33 per cent) and fever (29 per cent).

At the 2011 ASH Annual Meeting, prolonged treatment data were reported from 17 patients with a median duration of treatment of 17.3 months (approximately 24 cycles of every three week dosing). The overall objective response rate with extended treatment was 88 per cent, including 76 per cent complete remissions and 12 percent partial remissions. Adcetris was generally well-tolerated, with the most common adverse events being peripheral neuropathy (71 per cent), upper respiratory infection (53 per cent) and fatigue (47 per cent). Prolonged treatment with Adcetris was associated with clinically meaningful durations of response without worsening of toxicity over time.

Adcetris is currently not approved for retreatment and extended duration beyond 16 cycles of therapy in relapsed HL and sALCL.

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. Systemic ALCL is an aggressive type of T-cell non-Hodgkin lymphoma that also expresses CD30.

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 tumour cells.

Adcetris  was granted accelerated approval by the FDA in August 2011 and approval with conditions by Health Canada in February 2013 for two indications: the treatment of patients with 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 the treatment of patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. The indications for ADCETRIS are Adcetris ponse 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 the treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma (HL): following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option. AAdcetris  is indicated for the treatment of adult patients with relapsed or refractory sALCL.

Seattle Genetics and Millennium are jointly developing Adcetris. Under the terms of the collaboration agreement, Seattle Genetics has US 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.

Seattle Genetics is a biotechnology company focused on the development and commercialization of monoclonal antibody-based therapies for the treatment of cancer.