Seattle Genetics is ditching further development of its clinical-stage acute myeloid leukemia (AML) candidate lintuzumab (SGN-33) after a Phase IIb trial failed to show the drug extended overall survival. The firm says it will now focus on the rest of its clinical pipeline, headed by the Phase III-stage Hodgkin lymphoma drug, brentuximab vedotin, which is being developed in collaboration with Millennium Pharmaceuticals.
Lintuzumab is a naked mAb targeting CD33. The Phase IIb study evaluated the drug in combination with low-dose cytarabine chemotherapy in 211 previously untreated AML patients aged 60 years or older who were ineligible for or declined intensive chemotherapy. Seattle said it was “disappointed” that the trial failed to show an overall survival benefit associated with lintuzuab in this older patient population.
Seattle’s lead candidate, brentuximab vedotin, is an antibody-drug conjugate comprising an anti-CD30 monoclonal antibody linked to monomethyl auristatin E (MMAE). Top-line data from a pivotal study evaluating brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma is under way under a Special Protocol Assessment with the FDA at multiple sites in North America and Europe. The firm says top-line data from the trial is expected within the next six weeks, and a regulatory submission could be filed within the first half of 2011. A Phase II clinical trial evaluating brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma (ALCL) is also due to report interim top-line data within the next six weeks. Seattle hopes systemic ALCL may provide an additional registration pathway for the drug. Meanwhile, in May the firm and its partner, Millennium, initiated a Phase III trial (designated Aethera) to investigate brentuximab vedotin in the treatment of patients at high risk of residual Hodgkin lymphoma following autologous stem cell transplant.
The firms inked their worldwide agreement to develop brentuximab vedotin during December 2009. Under the terms of the agreement, Seattle Genetics and Millennium's parent company, Takeda Group, are sharing worldwide development costs on a 50:50 basis. Seattle received an up-front payment of $60 million, and retains full commercialization rights to brentuxiamb vedotin in the U.S. and Canada. Takeda has exclusive rights to commercialize the product in all other countries in return for development and sales milestone payments, which Seattle says could reach over $230 million.
Seattle's clinical pipeline also includes antibody-drug conjugates and an engineered monoclonal antibody in Phase I trials. Dacetuzumab (SGN-40) is a humanized mAb targeting the CD40 antigen and is currently undergoing four Phase Ib clinical trials as combination therapy against non-Hodgkin lymphoma and multiple myeloma.
SGN-70 is a humanized anti-CD70 mAb in a Phase I trial in patients with autoimmune disease, and SGN-75 is a humanized anti-CD70 mAb attached to the synthetic drug payload, monomethyl auristatin F (MMAF). Developed using Seattle’s antibody-drug conjugate (ADC) technology, SGN-75 is currently undergoing a Phase I clinical trial in patients with relapsed or refractory non-Hodgkin lymphoma or metastatic renal cell carcinoma.
ASG-5ME is an antibody-drug conjugate comprising a fully human monoclonal antibody targeting the anticancer target SLC44A4 (AGS-5), attached to monomethyl auristatin E (MMAE) via an enzyme-cleavable linker designed to release the cytotoxic agent only once it has been delivered to antigen-expressing cancer cells. A single-agent, open label dose-escalation trial evaluating the safety, tolerability, pharmacokinetics, and antitumor activity of ASG-5ME is under way in patients with metastatic pancreatic cancer.