Positive effects with Genasense in relapsed NHL

Antisense company Genta has reported positive clinical data on the safety and activity of Genasense (oblimersen sodium) injection, the company's lead anticancer drug, in combination with rituximab (Rituxan; Genentech IDEC). The trial was conducted in patients with relapsed and refractory non-Hodgkin's lymphoma (NHL).

In this study, Genasense was administered daily for seven days on weeks one, three and five, and rituximab was administered weekly for six weeks. Thirty-five patients who had failed a median of two prior chemotherapy regimens with or without rituximab were entered into this ongoing trial. To date, six patients have achieved a complete response, one of whom was refractory to prior rituximab therapy. Nine other patients have achieved a partial response for an overall response rate of 42%. Patients with the specific subset of follicular lymphoma showed a response rate of 56%. Twelve other patients have had stable disease. Side effects of the combination appeared qualitatively similar to that for rituximab alone, including but not limited to neutropenia, fever, infection, anaemia and fatigue.

Prior studies have shown preclinical synergy of Genasense with rituximab in NHL (1,2). The concurrent treatment schedule employed in this clinical study closely follows the optimised dosing regimen that was recently described for the use of this combination (3). This study - the first to report clinical activity of Genasense plus rituximab without the use of cytotoxic chemotherapy - was supported in part by the National Cancer Institute. Recent clinical studies have also demonstrated safety and activity when using Genasense and rituximab in combination with chemotherapy, such as CHOP-R in patients with mantle cell lymphoma (4). Ongoing work is also assessing the use of Genasense in combination with rituximab plus fludarabine in patients with chronic lymphocytic leukemia (CLL).

'The Genasense-rituximab combination trials are high priorities for the Company in both NHL and CLL', commented Dr Loretta Itri, president, pharmaceutical development and chief medical officer for Genta. 'We anticipate that future registration trials in both of these indications will incorporate the use of rituximab. These early demonstrations of safety and activity are key to the translation of promising preclinical work into patients, as well as for building the combination regimens for new trials in these diseases.'