Novartis has expanded its late-stage oncology pipeline through an exclusive licensing agreement with Antisoma plc for the worldwide rights to AS1404, a small molecule vascular disrupting agent expected to begin phase III trials in 2008 in patients with squamous non-small cell lung cancer.
"This agreement further strengthens our broad and deep oncology pipeline by adding a novel mechanism to treat solid tumours," said David Epstein, President and CEO of Novartis Oncology. "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."
Novartis reached this agreement following the presentation in November 2006 of positive phase II results involving patients with non-small cell lung cancer that showed AS1404 extended median survival by five months when used in combination with a standard chemotherapy regimen of paclitaxel and carboplatin over chemotherapy alone. Recently reported results of a confirmatory phase II trial in non-small cell lung cancer showed a response rate of 50 per cent in AS1404 patients, while another 43 per cent showed disease stabilization.
AS1404, given as a 20-minute infusion immediately following chemotherapy, is the first compound in this new class of compounds called vascular disrupting agents (VDAs) to report positive data from a randomised phase II clinical trial.
These compounds selectively disrupt established blood vessels in solid tumours, which rely on a network to survive and grow. VDA compounds exert an effect different to angiogenesis inhibitors, which inhibit the formation of new tumour blood vessels.
The need for new lung cancer treatments is urgent since it is one of the most common cancers worldwide with low survival rates. About 1.2 million deaths worldwide are linked to lung cancer each year. Non-small cell lung cancer represents about 80 per cent of all lung cancer cases. The squamous form is one of three NSCLC types and represents 25 per cent to 40 per cent of cases.
Initial data from other phase II trials in ovarian and prostate cancers have shown increased response rates through the addition of AS1404 to standard chemotherapy. The potential benefits of this compound in these cancers, as well as other solid tumours, will be further explored during the development programme.
The addition of AS1404 to the Novartis pipeline brings to seven the number of compounds planned to enter late-stage development by the end of 2008. In addition to AS1404, other compounds include RAD001 (multiple tumours), SOM230 (Cushing's disease/refractory carcinoid tumours, acromegaly), LBH589 (chronic myeloid leukaemia cutaneous T-cell lymphoma), Tasigna (chronic myeloid leukaemia), EPO906 (ovarian), and PKC 412 (acute myelogenous leukaemia).