Genta Incorporated announced results from several studies that suggest Genasense (oblimersen sodium), the company’s lead anticancer compound, enhances the activity of many types of chemotherapy in patients with multiple myeloma. Three investigative groups at the annual meeting of the American Society of Hematology (ASH) presented the results.

Bcl-2, the protein target of Genasense therapy, is expressed at high levels in patients with myeloma. The protein has been shown to block the onset of myeloma cell death that would otherwise be triggered by chemotherapy. By blocking production of Bcl-2, Genasense may overcome the inherent resistance of myeloma to anticancer treatment. Genta is broadly exploring the use of Genasense as a means of enhancing the activity of chemotherapy for myeloma in Phase 2 and Phase 3 trials.

In a Phase 1-2 clinical study, 25 patients with advanced myeloma were treated with escalating doses of Genasense and thalidomide, plus high-dose dexamethasone. All patients had received extensive prior therapy. Twenty-three of 25 (92per cent) had previously progressed despite having undergone stem cell or allogeneic transplantation. All had previously received dexamethasone, and 11 had previously received thalidomide. To date, 20 patients have completed induction therapy and are evaluable for response. Twelve of the 20 patients (60per cent) have achieved a major clinical response, including 2 complete responses, 4 near-complete responses, and 6 partial responses. Four other patients had a minor response. With a median of 7.5 months, only 1 patient has relapsed, and 16 patients remain on study.

In the second clinical study ten patients with refractory myeloma participated, 8 of who were refractory to a standard drug combination known as “VAD” (vincristine, doxorubicin, and dexamethasone). Patients were treated with Genasense plus VAD. Of the 9 patients who are currently evaluable, 4 have achieved a partial response, and 3 have achieved a minor response.

Finally, in a preclinical study, Genasense was combined with bortezomib in models of myeloma and non-Hodgkin’s lymphoma. Using 6 different cell lines, Genasense was shown to amplify the apoptotic activity of Velcade.

“Multiple myeloma is the focus of considerable attention at Genta. Enrollment into our Phase 3 multiple myeloma trial has completed and will provide further clinical evaluation of the Genasense/dexamethasone regimen that was presented today,” observed Dr Loretta M Itri, Genta’s president, Pharmaceutical Development.

About Multiple Myeloma Multiple myeloma is a cancer that arises in blood cells (called plasma cells) that normally reside in the bone marrow. Plasma cells normally produce antibodies that fight off infections. When cancer develops in plasma cells, these cells markedly increase in number, which can cause severe bone pain and fractures; however, their ability to produce antibodies is actually greatly reduced. Therefore, people with these conditions are highly susceptible to infections. Malignant plasma cells are known to contain a high amount of Bcl-2 protein, which is targeted by Genasense.