Cell Therapeutics' Xyotax holds much promise for few patients

Cell Therapeutics has announced positive phase III data for Xyotax in non-small cell lung cancer, with the drug significantly increasing survival in pre-menopausal female patients with high estrogen levels. However, with such a limited patient population, Xyotax will struggle to compete with Sanofi-Aventis' Taxotere, Eli Lilly's Gemzar and genericized paclitaxel in cost-constrained markets.

Xyotax (paclitaxel poliglumex) is a novel biologically-enhanced version of Bristol-Myers Squibb's Taxol (paclitaxel) - one of the most-commonly used oncology drugs. Xyotax consists of paclitaxel linked to a biodegradable polyglutamate polymer, which reduces the toxicity and administration issues traditionally associated with paclitaxel. This allows Xyotax to become preferentially trapped in tumor blood vessels, allowing more paclitaxel to localize in the tumor.

R&D

Two phase III studies - STELLAR-3 and STELLAR-4 - investigated the role of Xyotax in the management of advanced non-small cell lung cancer (NSCLC) patients with Eastern Cooperative Oncology Group (ECOG) poor performance status scores. Composite analysis revealed that Xyotax improved overall survival in female patients, with the greatest survival benefits found within the pre-menopausal population. Xyotax failed to improve survival in male NSCLC patients.

For women under the age of 55, Xyotax significantly improved overall survival compared with the control arm, but failed to do so in the over-55s.

In the STELLAR-3 trial, patients with pre-menopausal estrogen levels (serum estrogen >30pg/mL), regardless of age, had a significant improvement in median survival when treated with Xyotax plus carboplatin, compared to patients treated with paclitaxel plus carboplatin. However, Xyotax failed to improve survival in females with post-menopausal estrogen levels (serum estrogen <30 pg/mL).

According to the US National Comprehensive Cancer Network, lung cancer remains the leading cause of cancer-related worldwide mortality in both men and women. With NSCLC comprising over 75% of all lung cancers, Datamonitor estimates that, during 2006, over 338,000 cases will be diagnosed in the seven major pharmaceutical markets. In addition, despite two decades of extensive R&D and chemotherapy use, the overall survival of NSCLC patients remains below 12 months.

Limited patient population

Following the FDA's recent decision to grant Xyotax fast track status, the future for the agent looks promising. Although the survival benefits demonstrated in the STELLAR trials offer hope for advanced, poor-performance, pre-menopausal female NSCLC patients, Xyotax' PIONEER-1 phase III trial is expected to be key to the agent gaining approval as it is the first gender-specific cancer trial.

However, even if Xyotax were to reach the market, its patient population would be limited by gender, patient performance status, and by the fact that over 50% of the NSCLC population are aged 65 or older.

Nevertheless, if Xyotax can repeat the positive performance shown in the PGT-202 phase II study in phase III trials involving advanced patients of both genders, the agent's commercial potential will be broadened.

Even so, Cell Therapeutics may find the restricted NSCLC market tough to penetrate given stiff competition from Sanofi-Aventis' Taxotere and Eli Lilly's Gemzar, which are routinely combined with cisplatin or carboplatin and form the backbone of traditional NSCLC regimes. Furthermore, paclitaxel is already genericized and, due to the cost containments of many healthcare systems, will remain a popular choice for physicians.

Viscosity problems have also been linked with Xyotax, which could further reduce Xyotax' patient potential. Cell Therapeutics, therefore, clearly still has a tough battle to fight for Xyotax - both within and beyond the clinical setting.

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