Seattle Genetics, Inc has reached agreement with the US Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) for a pivotal trial of SGN-35, an antibody-drug conjugate (ADC), for patients with relapsed or refractory Hodgkin lymphoma. The SPA provides an agreement between the FDA and Seattle Genetics regarding the design, including size and clinical endpoints, of the pivotal trial to support an efficacy claim in a New Drug Application (NDA).

The single-arm pivotal trial will assess efficacy and safety of single-agent SGN-35 in 100 patients with relapsed or refractory Hodgkin lymphoma who previously received autologous stem cell transplant. Patients will receive 1.8 milligrams per kilogram (mg/kg) of SGN-35 every three weeks. The primary endpoint of the trial will be objective response rate assessed by an independent radiographic facility. Secondary endpoints include duration of response, progression-free survival, overall survival and tolerability. The company plans to enrol patients at more than 30 sites in the US, Canada and Europe.

"Reaching this agreement with the FDA on an SPA for Hodgkin lymphoma is an important part of our regulatory strategy for SGN-35 and positions us to initiate the pivotal trial in the first quarter of 2009. Our goal is to submit an NDA in 2011 under the accelerated approval regulations," said Clay B Siegall, president and chief executive officer of Seattle Genetics. "The data thus far from both of our phase I trials of SGN-35 have exceeded our expectations, including multiple complete and partial responses at well-tolerated doses, suggesting that this agent may address a substantial unmet medical need in patients with relapsed or refractory Hodgkin lymphoma."

Seattle Genetics also plans to conduct a phase-II study of single-agent SGN-35 in approximately 50 patients with relapsed or refractory systemic anaplastic large cell lymphoma (ALCL), which is also expected to begin in the first quarter of 2009.

"Based on recent discussions with the FDA, we believe that the most efficient path forward for SGN-35 in ALCL is to forgo an SPA and conduct a phase-II trial designed to further define the response rate and tolerability profile in this patient population," added Dr Siegall. "To date, five of six ALCL patients treated in our phase-I trials of SGN-35 have achieved complete responses, indicating that SGN-35 has strong therapeutic potential in this setting. We plan to advance the ALCL study in parallel with our pivotal trial in Hodgkin lymphoma."

Data from a phase-I dose-escalation clinical trial of SGN-35 were presented in December 2008 at the American Society of Haematology annual meeting. Among 28 evaluable patients with relapsed or refractory Hodgkin lymphoma or ALCL treated at doses of 1.2 mg/kg and higher administered every three weeks, 54 per cent achieved an objective response, including 32 per cent with complete responses. Furthermore, 93 per cent of these patients achieved tumor reductions and median progression-free survival was greater than six months. SGN-35 was generally well tolerated. The majority of adverse events were Grade 1 and 2, with the most common being fatigue, fever, diarrhoea and nausea. The company is also continuing dose escalation in an ongoing phase I clinical trial of SGN-35 administered on a weekly basis, and expects to report data from this study during 2009.

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.