Melbourne, Australia; 25 May 2016: Starpharma Holdings Ltd (ASX: SPL, OTCQX: SPHRY) today announced that Starpharma’s DEP™ cabazitaxel eliminated neutropenia typical of cabazitaxel (Jevtana^®) in a preclinical study (see Figure 1). Neutropenia is a common and life-threatening side-effect of currently available chemotherapy drugs including Jevtana^® (cabazitaxel).  The data from this animal study follows on from similar findings with other DEP™ candidates and recently announced findings demonstrating that Starpharma’s DEP™ cabazitaxel significantly outperformed Jevtana^® with respect to the level and duration of anticancer activity, and overall survival (see Figure 2).

DEP™ cabazitaxel is Starpharma’s dendrimer-enhanced, detergent free version of the leading cancer drug, Jevtana^® (cabazitaxel) which is currently registered for use in advanced prostate cancer and had 2015 sales of ~US$430M. Jevtana^®, like Taxotere^® (docetaxel), is formulated using a detergent, polysorbate 80, due to its poor solubility and is associated with anaphylaxis and neutropenia. Jevtana^® has a FDA “black box” warning regarding neutropenia and severe hypersensitivity to polysorbate 80. In contrast, Starpharma’s DEP™ cabazitaxel is water soluble and completely detergent (polysorbate 80) free.

Neutropenia, characterised by low neutrophil (white blood cell) levels in the blood, is a sign of bone marrow toxicity and the most important dose limiting toxicity (DLT) of Jevtana^®. Severe neutropenia (extremely low circulating neutrophil numbers) is a life-threatening and potentially fatal toxicity that occurs in more than 80% of patients treated with Jevtana^®. Neutropenia can necessitate anti-cancer treatment modification, interruption or discontinuation. 

Jevtana^® is currently used in the treatment of advanced prostate cancer that has worsened (progressed) after treatment with docetaxel, and is under clinical development for breast cancer and other cancers.  

“These results are very pleasing for our DEP™ cabazitaxel formulation, as they show the platform benefits of our DEP™ dendrimers in enhancing the therapeutic window - decreased bone marrow toxicity and enhanced efficacy - of drugs,” said Starpharma Chief Executive Officer, Dr Jackie Fairley. “The combination of these benefits for DEP™ cabazitaxel provide compelling commercial advantages. The fact that these results are similar to those seen previously with DEP™ docetaxel and other classes of DEP™ enhanced therapeutics demonstrates the platform nature of the DEP™ technology.” she added.

Description of Study

The relative toxicities of DEP™ cabazitaxel and Jevtana^® were compared in a preclinical study where equivalent doses (based on cabazitaxel - 2.5mg/kg) were administered to rats by intravenous injection. Blood samples were taken at day 0 prior to dosing, then at days 5, 7, 14 and 21 and cell counts undertaken. The neutrophil counts, expressed as the mean absolute count across all animals in the dose group (n=3 per group), at each time point are shown in Figure 1. These studies were conducted by an independent commercial laboratory which specializes in preclinical oncology services.  

Figure 1:  Neutrophil counts over 21 days (expressed as mean neutrophil counts) of animals treated with a single dose of either a vehicle control, Jevtana^® or DEP™ cabazitaxel, showing the lack of neutropenia in animals treated with DEP™ cabazitaxel. In contrast, Jevtana^®-treated rats exhibited severe neutropenia within the first week following drug treatment.

Figure 2.    Efficacy of DEP™ cabazitaxel vs. Jevtana^® (cabazitaxel) and vehicle in preclinical model of human breast cancer. For full details refer to 4 April 2016 announcement, see DEP cabazitaxel shows complete and sustained tumour regression in breast cancer model (pdf file, 173kb)

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