Melbourne Australia: Starpharma Holdings Ltd (ASX: SPL; OTCQX: SPHRY) today announced additional positive results for its dendrimer formulation of the major chemotherapeutic, docetaxel (Taxotere^®), ahead of its advancement into clinical trials later this year.

In the preclinical study, animals treated with Starpharma’s Dendrimer-Docetaxel formulation exhibited a lack of neutropenia.  In contrast, animals treated with Taxotere^®  in this study exhibited severe neutropenia, a sign of bone marrow toxicity and the most important dose-limiting side effect of Taxotere^®.

Docetaxel, which is now generic, has reported annual sales of $3.1 billion.  The originator is marketed worldwide under the trade name Taxotere^®. 

Severe neutropenia (abnormally low circulating neutrophil numbers) is a life threatening toxicity that occurs in more than 75% of patients[1] treated with docetaxel (Taxotere^®).  Neutrophils are a type of white blood cell, so severe neutropenia exposes the patient to a high risk of serious infection and requires modification to dosing schedules, rescue therapy with expensive drugs, and additional clinical management.  Taxotere^® has an FDA “black box” warning in its product information regarding neutropenia including contraindications and management requirements for certain patients.

“These latest results are really very positive for our Dendrimer-Docetaxel formulation in the lead up to its move into the clinic,” said Starpharma Chief Executive Officer, Dr Jackie Fairley.

“We have now shown that Starpharma’s dendrimer technology can prevent neutropenia as observed in independent studies of two leading cancer drugs, docetaxel and oxaliplatin. These findings suggest that the ability to avoid these important toxicities is likely to be a feature of the dendrimer platform and therefore, could also be anticipated with other cancer drugs.”

Starpharma’s proprietary Dendrimer-Docetaxel formulation has also previously been reported to show other significant benefits compared to Taxotere^®.  In its preclinical development, the Dendrimer-Docetaxel formulation has been shown to:

• be water soluble (removing the need for Polysorbate 80, a detergent which is present in Taxotere^® and most other formulations of docetaxel, and which causes the serious toxicity, anaphylaxis)
• have excellent drug targeting to tumour tissue (more than 40 times greater levels than Taxotere^®)
• have a markedly extended half-life (60 fold increase in plasma half-life), and
• have significantly enhanced anticancer effect when compared to Taxotere^®.

“When all these advantages and clinically significant benefits of the Starpharma Dendrimer-Docetaxel formulation are placed alongside the latest findings of a lack of neutropenia, it places the dendrimer formulation in a very compelling competitive position.  It is particularly pleasing to have these latest findings ahead of taking the product into the clinic later this year,” said Dr Fairley.

Description of Study

This study was conducted as part of the pre-clinical program ahead of commencement of clinical trials.  The relative toxicities of the Dendrimer-Docetaxel formulation and Taxotere^® were compared in a study where equivalent doses (based on docetaxel; 9mg/kg) were administered to male and female rats by intravenous injection on Day 0.  Blood samples were taken at day 0 prior to dosing, then at days 7, 14 and 21.  The level of neutrophils, expressed as the mean absolute count across all animals in the dose group (n=6 per group), at each time point are shown in Figure 1.

Figure 1: Neutrophil levels as measured weekly over 21 days, showing the lack of neutropenia in animals treated with the Dendrimer-Docetaxel formulation. In contrast, Taxotere® treated mice show marked neutropenia and the typical rebound neutrophilia, which follows.

As can be seen from Figure 1, the neutrophil counts of the Dendrimer-Docetaxel formulation treated rats remained normal throughout the study.  Rats treated with Taxotere^® exhibited a significant neutropenia resembling the neutropenia that is commonly seen in humans.  These results indicate that the Dendrimer-Docetaxel formulation did not cause neutropenia.  

In this study, the Dendrimer-Docetaxel formulation treated rats were also free from other bone marrow toxicities such as thrombocytopenia (low platelets) which were observed in Taxotere^® treated animals. 

“The potential to be able to use docetaxel with reduced need for expensive rescue therapies or additional hospital stays represents an important advance for patient care.  Apart from better patient outcomes, the potential savings for constrained health-care budgets are also very attractive,” Dr Fairley added.

Whilst Starpharma’s most advanced drug delivery program is docetaxel, the technology has value more broadly as it can be applied to a wide variety of drugs (including proteins, antibodies, hormones) in addition to being particularly valuable in cancer treatments.  The company recently announced its dendrimer-enhanced formulation of oxaliplatin, a leading treatment for colon and colorectal cancer, significantly reduced bone marrow toxicity and neurotoxicity in preclinical studies.