Italian oncology drug development firm Novuspharma SpA is moving its lead molecule, the non-Hodgkin¿s lymphoma (NHL) treatment BBR 2778, to pivotal Phase III studies in the first quarter of the new year, following its disclosure of encouraging Phase II data in patients with the relapsed, aggressive form of the disease.

Nine of the 33 participants responded to the treatment, which was administered as a monotherapy. Five exhibited a complete tumor response, defined as complete disappearance of all lesions, while the remaining four displayed a partial response, defined as a reduction in lesion size of at least 50 percent. Most of the patients had relapsed following earlier chemotherapy that included doxorubicin treatment, a current gold standard treatment, the Bresso-based company said.

In addition to the efficacy data, the company also has observed sustained responses in patients from earlier trials. ¿We do have patients that are responsive for more than one year and that is encouraging,¿ said Novuspharma¿s head of development, Gabriella Comboni.

Novuspharma plans to start enrollment for two separate Phase III trials of BBR 2778 in the first quarter of the new year, involving patients with aggressive and indolent forms of NHL, respectively. It will recruit 700 participants for each study, Comboni said. The two forms of NHL can be distinguished on the basis of their histologic profiles. Those with indolent lymphomas, which grow more slowly, have longer survival from first diagnosis, but there is no cure and the patient dies after multiple relapses. Those with the aggressive form may respond fully to treatment.

Dose-escalation studies of BBR 2778 in combination with cisplatin and Ara-C, a common treatment for relapsed NHL, are ongoing. Two additional combination studies, involving fludarabine, cyclophosamide and vincristine, are due to commence shortly in patients with the aggressive form of the disease, Comboni said.

Dose-escalation studies are not required in indolent NHL, she said, as BBR 2778 will be used in combination with the monoclonal antibody rituximab, which is not cytotoxic.

BBR 2778 is an intercalating agent, which was discovered and developed in collaboration with the University of Vermont. ¿It is reasonably well tolerated, but it is cytotoxic,¿ Comboni said. ¿With BBR 2778 we have suppression of white blood cells and, to a much lesser degree, platelets.¿

Animal data indicate that it may have less cardiotoxic effects than other intercalating agents such as doxorubicin, she said, although the company will not be able to demonstrate this in clinical trials.

Novuspharma, which has three other programs at the Phase II stage, has its roots in the oncology R&D department of Boehringer Mannheim Italia SpA. It was spun off as an independent company in 1998 by F. Hoffmann-La Roche Ltd., of Basel, Switzerland, following the latter company¿s acquisition of Boehringer. It is well funded, having raised EUR155 million (US$140 million) in Europe¿s fourth largest biotechnology IPO last year. The company exited the third quarter with EUR 147.6 million in cash.

The company has had preliminary partnering discussions on BBR 2778, but does not plan to enter agreements in the near term. ¿We are talking to companies that are interested. We haven¿t anything firm yet. We are waiting until we are closer to the NDA,¿ Comboni said.

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