Novartis added another late-stage drug to its cancer pipeline yesterday after it licensed rights to Xyotax – a long-acting paclitaxel product in Phase III studies as a treatment for non-small cell lung cancer in women – from US biotech Cell Therapeutics.
The Swiss drug major also has a $111.5 million option to develop pixantrone, a drug in Phase III trials that is designed to improve the treatment of haematological cancers by boosting the activity and reducing the toxicity of the commonly-used anthracyclines.
Xyotax (poliglumex paclitaxel) is a new chemical entity that is designed to boost paclitaxel’s anticancer activity by delivering more active drug to tumour cells. Paclitaxel is bound to a biodegradeable polymer that renders it inactive until it reaches cancer cells, so treatment should also be less toxic than with current paclitaxel-based products.
The ongoing PIONEER 1 trial of Xyotax, which got underway last December, is enrolling 600 women with NSCLC, because the drug is known to preferentially deliver its payload to tumour cells bearing oestrogen receptors. Exposure of lung cancer cells to oestrogen increases the gene expression of cathepsin B, a critical enzyme that metabolizes Xyotax, releasing active paclitaxel within the cell.
If successful, Xyotax could emerge as the first gender-specific treatment for NSCLC, and accelerate work in other cancers known to express the oestrogen receptor. Several studies have shown that, compared to men, women who smoke are more likely to develop lung cancer at a younger age and at lower levels of exposure to cigarette smoke, while non-smoking women are also at a higher risk for developing lung cancer than non-smoking men.
Before the gender-specific effects of Xyotax were identified, Cell Therapeutics suffered some major disappointments in Phase III trials involving both men and women, including the STELLAR 3 and 4 studies which found no improvement in efficacy compared to standard chemotherapy in NSCLC. An analysis of combined data from women enrolled in the two trials reinvigorated the project.
Novartis is making $15 million equity investment in Cell Therapeutics as part of the deal, giving it an 8% stake in the firm, with the remaining $270 million coming from development and sales milestones.
If Xyotax is approved, Cell Therapeutics retains an option to co-promote the drug, giving it an opportunity to rebuild its salesforce. This was disbanded after the company sold rights to its Trisenox (arsenic trioxide) leukaemia drug to Cephalon for $170 million last year, in order to fund further development of Xyotax.