Seattle Genetics, Inc. (Nasdaq:SGEN) announced that it has completed enrollment of its pivotal clinical trial of brentuximab vedotin (SGN-35) for relapsed and refractory Hodgkin lymphoma. Brentuximab vedotin is an antibody-drug conjugate (ADC) targeted to CD30 utilizing the company's proprietary ADC technology.
"Strong interest in brentuximab vedotin from investigators and patients has allowed us to rapidly complete our target enrollment of 100 patients in the pivotal trial in six months, emphasizing the substantial unmet medical need in the relapsed and refractory Hodgkin lymphoma setting," said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "The pivotal trial allows for patient treatment up to approximately one year, and we expect data to be available in the second half of 2010. Our goal is to submit both a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) under the accelerated approval regulations and a Marketing Authorization Application (MAA) with the European Medicines Agency (EMEA) for conditional marketing authorization in the first half of 2011. Assuming priority review of our NDA, we would then plan to commercially launch the drug in the United States in the second half of 2011, with potential European launch to follow."
The brentuximab vedotin pivotal trial is a single-agent, single-arm study evaluating 100 patients with relapsed or refractory Hodgkin lymphoma who previously received autologous stem cell transplant. Patients receive 1.8 milligrams per kilogram (mg/kg) of brentuximab vedotin every three weeks. The primary endpoint of the study is objective response rate assessed by independent review. Secondary endpoints include duration of response, progression-free survival, overall survival and tolerability. The pivotal trial is being conducted under a Special Protocol Assessment (SPA) from the FDA. The SPA is an agreement between the FDA and Seattle Genetics regarding the design of the pivotal trial, including size and clinical endpoints necessary to support an efficacy claim in an NDA. Brentuximab vedotin has also been granted fast track designation by the FDA for the treatment of Hodgkin lymphoma as well as orphan drug designation in the United States and Europe for both Hodgkin lymphoma and anaplastic large cell lymphoma (ALCL).
Brentuximab Vedotin Phase I Clinical Trials
In a phase I dose-escalation study, 45 patients received doses of brentuximab vedotin every three weeks, ranging from 0.1 milligrams per kilogram (mg/kg) to 3.6 mg/kg. Among 28 evaluable Hodgkin lymphoma and systemic ALCL patients treated at doses of 1.2 mg/kg and higher, the overall response rate was 54 percent based on investigator assessment, compared to 57 percent based on independent review. At the higher dose levels, 39 percent of patients achieved a complete response based on investigator assessment, compared to 32 percent based on independent review. The median duration of response was at least 7.3 months.
The company is also conducting an ongoing phase I dose-escalation trial of brentuximab vedotin administered weekly to patients with Hodgkin lymphoma or systemic ALCL. Interim data have shown that out of 20 evaluable patients treated at doses of 0.8 mg/kg and higher, 60 percent achieved an objective response, including 50 percent with complete responses. Across all dose levels, 81 percent of patients achieved tumor reductions.
In both phase I clinical trials, brentuximab vedotin has been generally well tolerated. The majority of adverse events were Grade 1 and 2, with the most common being fatigue, fever, peripheral neuropathy, diarrhea and nausea.
About Brentuximab Vedotin
Brentuximab vedotin is an ADC comprising an anti-CD30 antibody attached by an enzyme cleavable linker to a potent, synthetic drug payload, monomethyl auristatin E (MMAE), using Seattle Genetics' proprietary technology. The ADC is designed to be stable in the bloodstream, but to release MMAE upon internalization into CD30-expressing tumor cells, resulting in targeted cell-killing.
Seattle Genetics is also conducting a single-agent phase II study of brentuximab vedotin in relapsed and refractory systemic ALCL, as well as a phase II study evaluating the potential for retreatment with brentuximab vedotin in patients who have relapsed after discontinuing previous brentuximab vedotin therapy.
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