Novartis licences lead cancer candidate from Antisoma

With the addition of Antisoma's AS1404 (5,6-dimethyl xanthenone 4-acetic acid, DMXAA) Novartis' oncology pipeline will swell to 12 new molecular entities (NMEs) in clinical trials as the company looks to bolster its presence in the oncology market. Novartis have stated that they aim to bring seven of these into late stage development by the end of 2007. If approved, AS1404 will add to its current arsenal of anticancer treatments: Femara (letrozole), Glivec (imatinib), Sandostatin LAR (octreotide acetate) and Zometa (zoledronic acid). "This agreement further strengthens our broad and deep oncology pipeline by adding a novel mechanism to treat solid tumours,"​ said David Epstein, CEO of Novartis Oncology. The deal consists of near-term payments of $100m with $75m being paid immediately and a further $25m when AS1404 enters a phase III trial in lung cancer. Antisoma will be eligible for milestone payments of up to $890m and will also receive sales royalties and have a co-commercialisation option in the US. Novartis will fund all future development costs as well as the outstanding costs of the current Phase II trials. News of the deal comes nearly six months after Antisoma announced positive results against non-small cell lung cancer (NSCLC) in November 2006 from a Phase II clinical trial of AS1404 (DMXAA) when used in combination with the standard chemotherapy treatment of paclitaxel and carboplatin (Bristol-Myers Squibb as Taxol and Paraplatin) originally marketed by than with the chemotherapy alone. NSCLC is the most common form of lung cancer, accounting for approximately 80 per cent of the 1.2m deaths a year. The drug is expected to help the 25 to 40 per cent of patients suffering from squamous NSCLC who cannot take Roche and Genetech's Avastin (bevacizumab). Sales of Avastin reached $1.7bn in 2006. The trial showed that median survival rates of patients were increased by five months as well as reducing the risk of death by over 27 per cent. Two other Phase II trials have been conducted by the company to show that the treatment is effective in both prostate and ovarian cancers as well as being generally well tolerated. "As a potentially first-in-class tumour vascular disrupting agent, AS1404 represents an opportunity to provide physicians and patients with an innovative new treatment option,"​ said Epstein. Research by Liangli Zhao has shown that AS1404 down-regulates the genes involved with tubulogenesis which leads to the formation of imperfect blood vessels as well as increasing the probability of apoptosis in the endothelial cells that line the inside of blood vessels. The drug also causes a cascade of vasoactive molecules including tumour necrosis factor (TNF) and serotonin. These two combined effects cause a rapid shutdown of blood flow to the tumour leading to extensive tumour necrosis. Another potentially first-in-class drug is being developed by Oxigene. Zyprestatt (combretastatin A4 phosphate, CA4P) is a prodrug that works by a different mechanism to AS1404. It inhibits the tubulin protein that gives endothelial cells their shape, causing the blood vessels to collapse - starving the tumour of oxygen. Positive results of a Phase II trial of CA4P, in combination with paclitaxel and carboplatin, for patients with anaplastic thyroid cancer were published in December last year. Antisoma has said that it planned to use the cash injection to start an active programme of in-licensing and will examine opportunities to acquire other oncology companies to broaden its pipeline and give it the capacity to commercialise its own products. "This deal provides both extra resources and new strategic options for Antisoma. We plan to use it as a springboard to further expand our pipeline,"​ said Glyn Edwards, CEO of Antisoma.