Novartis announced that ASA404, its novel cancer agent, has entered into a phase III lung cancer trial following positive outcomes of a phase II trial. The novel mechanism of action of ASA404 may represent a new approach to treating the most prevalent cause of cancer death.

ASA404 is a Tumour-Vascular Disrupting Agent (Tumour-VDA) that selectively causes the collapse of existing tumour blood supply leading to extensive tumour cell death. The action of ASA404 is distinct from that of angiogenesis inhibitors, which inhibit the formation of new tumour blood vessels.

In a randomized phase II study, ASA404, in combination with chemotherapy, demonstrated a median overall survival advantage of more than five months in first-line treatment of advanced non-small cell lung cancer (NSCLC) compared with chemotherapy alone. A similar survival advantage was observed in a subsequent extension of the phase II study.
Non-small cell lung cancer, the potential lead indication for ASA404, accounts for about 85 per cent to 90 per cent of all lung cancers. Worldwide, lung cancer is the number one cause of death from cancer each year in both men and women, with 1.2 million new cases per year and 921,000 deaths.

"With the launch of ATTRACT-1, we look forward to exploring the unique mechanism of action of ASA404 in non-small cell lung cancer to potentially help the more than one million people who develop lung cancer each year," said Alessandro Riva, Executive vice president and global head of development of Novartis Oncology.

ASA404 is one of six novel oncology compounds Novartis is developing for potential registration over the next five years. The other investigational therapies which focus on a broad array of cancer targets include RAD001 (renal cell carcinoma and other cancers), SOM230 (Cushing's disease/refractory carcinoid tumours, acromegaly), LBH589 (cutaneous T-cell lymphoma and other cancers), EPO906 (ovarian cancer), and PKC412 (acute myelogenous leukaemia and aggressive systemic mastocytosis).

"Today, our broad and deep pipeline includes both small molecules and monoclonal antibodies that utilize a variety of mechanisms such as vascular-disruption, anti-angiogenesis, and kinase inhibition to treat cancer," said David Epstein, President and CEO of Novartis Oncology. "These exciting potential discoveries have the possibility to change medical treatment for patients suffering with many forms of cancer".

The trial will be a randomized, double-blind, placebo-controlled, multi-centre study of ASA404 in combination with paclitaxel and carboplatin as first-line treatment for locally advanced or metastatic (Stage IIIb/IV) NSCLC of squamous or nonsquamous histology.

ASA404 is a small-molecule tumour-VDA that selectively disrupts existing tumour blood vessels. Solid tumours rely on a network of blood vessels to survive and grow. ASA404 targets existing tumour blood vessels causing death of vessel endothelial cells and the collapse of tumoral blood vessels.

Novartis signed an exclusive licensing agreement with Antisoma plc for the worldwide rights to ASA404 in April 2007.