CuraGen and TopoTarget have begun patient dosing in a Phase II open-label, multicenter clinical trial evaluating the efficacy and safety of intravenous belinostat (PXD101), a small-molecule histone deacetylase (HDAC) inhibitor, in combination with Velcade in multiple myeloma patients refractory to or who have rapidly relapsed from at least one previous bortezomib-containing regimen.

Based on preliminary safety results from ongoing Phase Ib trials evaluating belinostat in combination with Velcade (bortezomib), CuraGen and TopoTarget have initiated this Phase II trial in multiple myeloma patients. Up to 35 patients are planned for study enrollment, with preliminary results anticipated by the end of 2007.

"Based on our preclinical studies that showed markedly increased anti-myeloma effects when belinostat was combined with bortezomib to treat a bortezomib-resistant myeloma in immunodeficient mice, we look forward to enrolling bortezomib-resistant multiple myeloma patients into this Phase II trial and determining whether the combination can provide clinical benefit to multiple myeloma patients that have failed, or who have relapsed on bortezomib therapy," James Berenson, the trial's principal investigator, said.

In vitro studies have shown that HDAC inhibitors and bortezomib, when combined, act synergistically through independent mechanisms leading to enhanced killing of cancer cells. Preclinical data suggest that when mice bearing bortezomib-resistant human tumors were treated with the combination of belinostat and bortezomib, greater inhibition of both tumor growth and circulating human IgG levels were observed than when either drug was used alone, and the mice tolerated the combination well without obvious adverse effects.

As this Phase II study of belinostat and bortezomib begins, CuraGen will close enrollment in the ongoing Phase Ib study of this combination in multiple myeloma.