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Novuspharma SpA Announces Plans for Phase I Trial of Pixantrone (BBR 2778) in Multiple Sclerosis

Promising Results in Pre-Clinical Models Pave the Way For Preliminary Clinical Studies

Dec. 2, 2002
Bresso, Italy

Novuspharma SpA, a biopharmaceutical company primarily focused on developing new cancer therapeutics, today announces plans to begin a phase I trial of pixantrone (BBR 2778) in patients with multiple sclerosis (MS) in early 2003. An outline of the planned trial was presented by Prof. Gonsette, of the Belgian National Centre for Multiple Sclerosis, on Saturday 30 November at the European Charcot Foundation meeting in Seville.

The trial is expected to recruit 15-20 patients in Europe. The main goal of this study is to define the dose of pixantrone to be used in longer term clinical trials, and to obtain preliminary activity data. Patients will receive four infusions of pixantrone every three weeks, with a starting dose of 120 mg/m2. The effect of pixantrone on patients' brain lesions will be assessed by magnetic resonance imaging (MRI) at the start of the trial and at two, four and six months thereafter. Pixantrone's cardiac safety profile will also be assessed at these time points by using a multiple gated acquisition (MUGA) scan to measure the left ventricular ejection fraction of the heart. Additional endpoints will include general safety and tolerability and number of pixantrone infusions required to induce significant lymphopenia (a reduction in the white blood cell count, pixantrone's primary mechanism of action in this indication).

The trial plans to enroll patients between the age of 18 and 55 with relapsing-remitting or relapsing-progressive MS, as defined by the McDonald criteria. Patients should have a disease duration of not more than 15 years and an Expanded Disability Status Scale Score (EDSS) between 1 and 5.5. Patients that have been treated with an immunosuppressor, such as mitoxantrone, in the past year will be excluded from the study.

At the same conference, a summary of previous pre-clinical data for pixantrone in MS was also presented. This included the results of a study in a chronic model of MS in rats (experimental autoimmune encephalomyelitis, EAE), which demonstrated that pixantrone was effective at preventing disease relapses and reducing white blood cell counts and suggested it was possibly more efficacious than mitoxantrone. This study also suggested an almost complete absence of cardiotoxicity compared to mitoxantrone.

In addition, new data for pixantrone in a chronic model of EAE in mice was also presented, which demonstrated that pixantrone was highly efficacious at preventing disease development, as well as being better tolerated than mitoxantrone. These data were generated by an independent group of scientists, led by Prof. Dr. B. Dubois from the University of Leuven in Belgium.

Mitoxantrone is currently the only treatment option for many patients with rapidly progressing forms of MS. However, its use is limited to 2-3 years due to its cumulative cardiotoxicity (see notes to editors).

Pixantrone is currently in phase III studies for the treatment of non- Hodgkin's lymphoma (NHL).

Mr. Silvano Spinelli, Chief Executive Officer, said: "If pixantrone's improved safety and efficacy profile is confirmed in the clinic, it should allow for the earlier and more prolonged treatment of severe MS patients. At Novuspharma we plan to continue our focus on developing improved cancer therapeutics but will not neglect the potential of our products in other therapeutic areas, which should prove attractive to partners wishing to conduct late stage development in these indications."

For further information, please visit the Company's website at

Multiple Sclerosis

Multiple sclerosis (MS) is a neurological disorder affecting approximately 1.5 million individuals world-wide. The disease normally starts in early to middle adulthood and is second only to trauma as the leading cause of neurological disability. The disease derives its name from the multiple areas of scarring that are found in the brains of affected subjects. Symptoms include weakness of the limbs, spasticity, bladder and gut dysfunction and disturbances of gait, vision and speech. MS is highly unpredictable and can vary from a benign illness to a rapidly evolving and incapacitating disease. The two commonest forms of MS are relapsing-remitting disease, which affects around 45% of patients and secondary progressive disease, which affects around 40% of patients. The majority of patients with relapsing-remitting disease progress to the secondary progressive form, although the time to progression is very variable.

Current treatments for Multiple Sclerosis

Current treatments for MS represent a potential $2 billion plus market, which is expected to grow to around $3 billion by 2004. The most commonly used treatments for relapsing-remitting MS are interferon beta (Avonex, Rebif and Betaferon) and glatiramer acetate (Copaxone). However, while clinical trials have confirmed the long term efficacy of these agents in relapsing-remitting MS, their efficacy appears to be limited in more advanced forms of the disease such as secondary progressive MS.

Currently mitoxantrone, an immunosuppressant drug, offers the only treatment option for many patients with severe MS (mitoxantrone is currently indicated for worsening secondary progressive, progressive relapsing and relapsing-remitting MS). Mitoxantrone has demonstrated efficacy in terms of reducing patient relapse rate, progression of disability and the severity of brain lesions as assessed by MRI scans. However, mitoxantrone suffers from the major drawback that it causes cumulative damage to heart muscle. This means that patients can only be treated with mitoxantrone for 2-3 years, otherwise they run the substantial risk of developing serious cardiac complications such as congestive heart failure.

Pixantrone (BBR 2778) and non-Hodgkin's lymphoma. Pixantrone (BBR 2778) 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 160,000 patients are estimated to be suffering from the disease in the US alone, projected to grow to 250,000 by 2007. Pixantrone has produced encouraging results to date, both from preclinical studies and from clinical trials. In particular, in phase II trials in patients with advanced aggressive NHL, pixantrone achieved 5 complete responses (CRs) and 4 partial responses (PRs) out of 33 patients. Currently Novuspharma is conducting a pivotal phase III trial in relapsed indolent NHL. This trial is expected to recruit around 800 patients in the US and Europe and will compare the efficacy and safety of pixantrone, in combination with rituximab (Rituxan(R)) to rituximab alone, with time to disease progression as the primary efficacy endpoint.

Novuspharma SpA

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 four products in clinical development and a dynamic research programme. Novuspharma's leading anti-cancer drug, pixantrone (BBR 2778), is in phase III clinical trials in indolent non-Hodgkin's lymphoma. Novuspharma was established in 1998 following the merger of Boehringer Mannheim and Hoffmann-LaRoche, to exploit the R&D team's proven track record in product development. Novuspharma makes use of a complete range of discovery and development platforms and focuses its specific expertise on the most critical part of the development process from the initial identification of leads to late clinical development stages as far as New Drug Application.

SOURCE Novuspharma SpA

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