Seattle Genetics, Millennium Brentuximab vedotin trial shows positive results

The single-arm pivotal trial assessed efficacy and safety of single-agent brentuximab vedotin in relapsed or refractory, post-autologous stem cell transplant (ASCT) Hodgkin lymphoma patients.

Brentuximab vedotin is an antibody-drug conjugate (ADC) comprising an anti-CD30 monoclonal antibody attached by an enzyme cleavable linker to a potent, synthetic drug, monomethyl auristatin E (MMAE) utilizing Seattle Genetics‘ proprietary technology.

The ADC employs a novel linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

In the trial, 75% of patients achieved an objective response as assessed by an independent central review using the stringent Cheson 2007 criteria, the primary endpoint of the trial, while 34% of patients achieved a complete remission.

Among patients achieving a complete remission, the median duration of response had not yet been reached at a median follow-up of approximately one year.

Tumor reductions were achieved in 94% of patients.

University of Cologne Internal Medicine professor Andreas Engert said he has rarely seen such response rates in this relapsed or refractory disease population and these data highlight Brentuximab vedotin as a potential addition to the treatment options for hodgkin lymphoma patients.

Based on recent discussions with the US Food and Drug Administration (FDA), Seattle Genetics plans to submit a biologics license application (BLA) in the first quarter of 2011 to seek approval for both relapsed or refractory hodgkin lymphoma and relapsed or refractory systemic anaplastic large cell lymphoma (ALCL).

However, Millennium has initiated discussions with European regulators to support the submission of a marketing authorisation application (MAA) to the European Medicines Agency (EMA) in the first half of 2011.