Melbourne, Australia; Starpharma (ASX: SPL, OTCQX: SPHRY) today announced further efficacy results of its most recent DEP™ candidate, DEP™ cabazitaxel, in a human breast cancer model. These data will be presented along with an overview of Starpharma’s DEP™ platform at the BioEurope Spring 2016 conference in Stockholm later this week.
DEP™ cabazitaxel is Starpharma’s dendrimer-enhanced, water soluble (detergent free) version of the leading cancer drug, Jevtana® (cabazitaxel). Jevtana® is marketed by Sanofi-Aventis with 2015 sales of ~US$430M growing at approximately 18% per annum. It is currently registered for use in advanced prostate cancer and is also under development for a number of other cancers, including breast cancer. Like docetaxel, Jevtana® (cabazitaxel) is formulated with a detergent (polysorbate 80) due to its poor solubility and can be associated with anaphylaxis and neutropenia. In contrast, DEPTM cabazitaxel is completely detergent free.
Starpharma’s DEP™ cabazitaxel was compared with Jevtana® in a human breast cancer preclinical model (xenograft). DEP™ cabazitaxel significantly outperformed Jevtana® with respect to both level and duration of tumour regression (anticancer activity). Within four weeks of dosing, 100% of mice treated with Starpharma’s DEP™ cabazitaxel were tumour-free and remained so for the duration of the extended study (150 days). In contrast, the Jevtana® treated group exhibited significant tumour regrowth from day 60 onwards (Figure 1). Tumour growth in both drug treated groups was significantly inhibited compared with the vehicle group (P<0.0001)[i].
DEP™ cabazitaxel also significantly outperformed Jevtana® in terms of survival in the model. DEP™ cabazitaxel treated animals showed 100% survival to the end of the experiment (150 days), and survival was significantly prolonged vs Jevtana® (Figure 2). The Jevtana® treatment group also had a significantly better survival outcome vs. vehicle group (P<0.0001)[ii].
Starpharma Chief Executive, Dr Jackie Fairley, commented, “We are very encouraged by these results for DEP™ cabazitaxel, our latest development candidate. The growing body of evidence of both efficacy-enhancement and survival benefits with DEP™ formulations is very positive and illustrates the utility and platform nature of Starpharma’s DEP™ technology.
“Early indications for DEP™ cabazitaxel are that it also demonstrates similar safety benefits to what we have seen with DEPTM docetaxel and other DEP™ conjugates in terms of reduced bone marrow toxicity. Additional benefits may also be seen as the DEP™ formulation is polysorbate 80 (detergent) free. The results from this study clearly demonstrate sustained efficacy and survival benefits for DEP™ cabazitaxel compared to Jevtana®, and follow recently-announced impressive sustained efficacy results with our HER2-targeted DEP™ conjugate.”
About Jevtana®
Jevtana® is an oncology product marketed by Sanofi-Aventis with 2015 sales of ~US$430M growing at approximately 18% per annum. Jevtana® is currently marketed for the treatment of hormone refractory metastatic prostate cancer and is also in clinical development for a variety of cancers including breast, bladder, head and neck, and others. Jevtana® often works in docetaxel resistant cancer types, but is generally associated with greater toxicity than docetaxel. Jevtana® has a ‘Black Box’ warning for the dose-limiting toxicity, neutropenia, and warnings due to anaphylaxis from polysorbate 80.
Study Methods
This human breast cancer cell line (MDA-MB-231) xenograft study was conducted for Starpharma by an internationally recognised translational cancer group as part of a wider program of studies to assess various DEP™ conjugates. A xenograft uses human breast cancer tissue in a mouse and is a well-established means of assessing efficacy of anticancer therapies including the Taxanes (docetaxel, cabazitaxel, etc.). Balb/c mice were inoculated subcutaneously with MDA-MB-231 breast cancer tissue (12 mice/group). Mice were dosed with Saline (Vehicle), DEP™ cabazitaxel or Jevtana® on days 1, 8 and 22. The drug treated groups were dosed at the maximum tolerated dose for each agent in the species. Tumour growth data were analysed by analysis of variance (ANOVA) followed by Dunnett’s post-hoc test. Survival curves were analysed using the Mantel Cox log rank test. The data represent the mean ± standard error of the mean (SEM). The experiment was ended on day 150.
