BRESSO, Italy, July 7, 2003 (PRIMEZONE) -- Novuspharma SpA (Other OTC:NVUSF) (Nuovo Mercato: NOV.MI and NOV IM), a biopharmaceutical company focused on developing new cancer therapeutics, today announces the results of a phase I combination trial for Pixantrone (BBR 2778), in which 58% (11/19) patients with relapsed aggressive non-Hodgkin's lymphoma (NHL) achieved an objective response with an impressive 32% achieving complete disappearance of their tumours. These results were presented during a poster session on 6 July, at the 32nd Annual Meeting of the International Society of Experimental Haematology, in Paris.
Pixantrone is a new generation DNA intercalator (a family of agents that include anthracyclines), which is currently in a phase III clinical trial for the treatment of NHL. Based on the extremely encouraging results announced today, Novuspharma plans to initiate a phase II trial in relapsed aggressive NHL, to further evaluate the efficacy and safety of this combination regimen, both as salvage therapy and as an induction regimen prior to bone marrow transplant.
Preliminary results of the phase I trial
This study was a phase I, open label, dose escalation trial, where Pixantrone was administered in combination with fixed doses of cytarabine, methylprednisolone and cisplatin (the so-called BSHAP regimen). This is a variation of the standard ESHAP regimen, where Pixantrone replaces etoposide; an alteration designed to improve response rates. The ESHAP regimen is typically used to treat patients with aggressive NHL who have relapsed following front-line treatment with an anthracycline containing regimen and who typically cannot tolerate additional anthracycline treatment due to the potential for significant cardiac toxicity. Preclinical studies demonstrated that Pixantrone has the lowest potential for cardiac side effects when compared to marketed DNA intercalators and anthracyclines (e.g. doxorubicin and mitoxantrone).
The BSHAP regimen was administered in a 21 day cycle. The primary objective of the study was to identify the recommended dose of Pixantrone to be used in phase II trials. All 19 patients were enrolled at the 80mg/m2 dose level, which was identified as the recommended dose for further trials. The majority of patients had resistant/refractory disease, having progressed a median of 124 days following prior chemotherapy. Responses were required to be maintained for 8 weeks or longer and were determined using the international workshop criteria for standardizing response evaluation in NHL.
Fernando Cabanillas MD, of MD Anderson Cancer Center in Houston, Texas, who was one of the investigators on the trial, commented: "There is currently a need for improved chemotherapy regimens in relapsed aggressive NHL, both for induction prior to bone marrow transplant and as salvage therapies in patients ineligible for this procedure. These phase I results demonstrate an encouraging activity and safety profile for Pixantrone in the BSHAP combination. Most impressive was the fact that 7/18 (39%) of patients achieved either a complete response or an unconfirmed complete response, with very acceptable toxicity. I look forward to further exploring its potential in the upcoming phase II trial."
Results: Out of 18 evaluable patients, there were six complete responses (CRs), one unconfirmed complete response (CRu), four partial responses (PRs), and six stable disease (SD) representing an overall response rate of 58% (11/19) and a disease control rate of more than 90% (17/18). These results represent an encouraging indication of anti-tumour activity, particularly with regards to the proportion of complete responses observed. Furthermore, several patients with a complete response were able to proceed to bone marrow transplant, suggesting that the BSHAP regimen has potential as an induction regimen before this procedure. Generally, the BSHAP regimen was well tolerated, with most patients receiving a median of 4 doses (range 1-6). Two patients experienced a dose limiting toxicity at 80mg/m2 (grade 3 infection, febrile neutropenia). For all 70 cycles of chemotherapy, grade 4 side effects were reported in 13 (neutropenia), 4 (anaemia), 1 (fever/neutropenia), 8 (thrombocytopenia). No clinically significant cardiac events were observed and no patient experienced a decrease in left ventricular ejection fraction (LVEF) of more than 20%.
Silvano Spinelli, Ph.D., CEO of Novuspharma commented: "These results validate our investment in the development of Pixantrone and further support the potential for Pixantrone to become a best-in-class DNA intercalator in the treatment of haematological cancers, like NHL."
On June 17, Novuspharma announced it had signed a merger agreement with Cell Therapeutics, Inc (CTI) (NASDAQ: CTIC), a Seattle, US based public biopharmaceutical company. As a result of this agreement Pixantrone is expected to benefit from CTI's strong haematology/oncology sales and marketing franchise in the US.
According to James A. Bianco, M.D., President and CEO of CTI, who during his career as a haematologist worked at the Fred Hutchinson Cancer Research Center and was the director of the Bone Marrow Transplant Program at the Veterans Administration Medical Center in Seattle: "Our enthusiasm about the market potential for Pixantrone stems from the robust clinical data, which demonstrates the ability to produce high rates of complete remission among patients who have previously failed prior anthracycline containing chemotherapy without observing significant cardiac side effects. This was one of the key considerations in our decision to merge with Novuspharma."
For further information, please visit the Company's website at www.novuspharma.com. For an explanation of technical terms please see www.novuspharma.com/nov/glossary/
Notes to Editors
Pixantrone (BBR 2778) and non-Hodgkin's lymphoma. Pixantrone is a DNA intercalator with improved efficacy and safety which Novuspharma is developing for non-Hodgkin's lymphoma (NHL). NHL is caused by the abnormal proliferation of lymphocytes (immune system cells) and is estimated to affect more than 276,000 patients in the U.S. NHL can be broadly divided into two forms, indolent NHL (a slow growing, chronic disease) and aggressive NHL (an acute form). Novuspharma is conducting a phase III trial for Pixantrone in indolent NHL, in combination with rituximab. Novuspharma is also running a number of supporting trials, in both aggressive and indolent disease, designed to demonstrate the broad potential of Pixantrone in lymphoma.
Relapsed aggressive non-Hodgkin's lymphoma (NHL)
The initial (front-line) treatment for aggressive NHL is the CHOP chemotherapy regimen. While this induces a high rate of remission, more than 60-70% of patients go on to experience a relapse. The prognosis for relapsed aggressive NHL is not good and the only procedure which can cure these patients is bone marrow transplant (see below). However, most patients are not eligible for this treatment due to their age, general health or the relapsed/progressive status of their disease.
Currently these patients receive chemotherapy combination regimens (such as ESHAP). However, normally these salvage regimens do not include highly active anthracycline or DNA intercalator drugs. This is because patients have typically received their maximum permitted exposure to these agents in front-line therapy and would risk significant cardiac toxicity if they were treated with a second course. Pixantrone is a DNA intercalator that has demonstrated an improved cardiac safety profile in preclinical and clinical studies and therefore has the potential to be used safely in these relapsed patients and boost the activity of current treatment regimens.
Bone marrow transplant. Officially: High-dose chemotherapy (HDC) with autologous bone marrow transplantation (ABMT) or peripheral stem cell transplantation (PSCT)
Autologous bone marrow transplant is the treatment of choice for relapsed aggressive NHL patients who are able to tolerate it, as this is the only procedure which has curative potential in these patients. Treatment normally starts with an induction chemotherapy regimen, such as ESHAP, which aims to reduce tumour burden and assess sensitivity to chemotherapy. If this is successful, the patient's bone marrow stem cells are mobilized, harvested and frozen for later use. High dose chemotherapy is then administered to eradicate any remaining tumour cells. While this is normally effective, it seriously depletes the patient's white blood cells and puts them at risk of infection. Therefore the patient's immune system is reconstituted by giving them an infusion of their own stem cells that were previously harvested.
There is a need for new, more effective, induction chemotherapy regimens that are better able to induce tumour response before the mobilisation and harvest of bone marrow stem cells. An improved induction regimen would allow more patients to undergo bone marrow transplant and therefore have a hope of curing their disease.
Novuspharma SpA and its merger agreement with Cell Therapeutics (CTI)
Novuspharma, based in Bresso, Milan, is an emerging biopharmaceutical company leveraging its expertise in the field of oncology to discover and develop innovative new treatments for cancer. It has three products in clinical development and a dynamic research programme. Novuspharma was established in 1998 following the merger of Boehringer Mannheim and Hoffmann-La Roche, to exploit the R&D team's proven track record in product development. On June 17, 2003, Novuspharma announced it had signed a merger agreement with Cell Therapeutics (CTI) of Seattle. CTI is a public biopharmaceutical company, which markets TRISENOXa in the US and Europe and is developing XYOTAXTM (CT-2103), which is in pivotal phase III trials for non-small cell lung cancer.
For further information, please visit the Company's website at www.novuspharma.com. For an explanation of technical terms please see www.novuspharma.com/nov/glossary/