Summary and Commercial Opportunity
Starpharma is developing an enhanced form of docetaxel known as DEP® docetaxel (dendrimer-docetaxel). The lead DEP™ docetaxel molecule is in Phase 1 clinical trials.
Docetaxel is a leading chemotherapy drug used to treat a wide range of solid tumours including breast, lung and prostate. It is marketed by Sanofi Aventis as Taxotere® and generated sales in excess of US$3 billion in 2010.
In pre-clinical studies DEP™ docetaxel was shown to have substantially better efficacy and lower toxicity than Taxotere® alone. Of particular significance was the absence of neutropenia, the major dose-limiting toxicity for Taxotere®.
DEP® docetaxel is water-soluble and does not require surfactant such as polysorbate 80 for dissolution. Drug substance is readily manufactured at scale using standard chemistry under cGMP.
Each DEP® docetaxel molecule comprises docetaxel attached to a dendrimer scaffold. The linker between the docetaxel and the dendrimer is designed to release the docetaxel in a controlled manner.
Therapeutic Potential and Benefits
Superiority to docetaxel/Taxotere® alone across multiple cancer types
In xenograft studies DEP™ docetaxel demonstrated a significant enhancement of anticancer effect when compared to docetaxel/Taxotere® alone. Furthermore, in the study 60% of animals treated with DEP® docetaxel had no evidence of tumours at 94 days - whereas 100% of the docetaxel treated mice showed significant tumour re-growth or recurrence at the same time point.
In hollow fibre studies DEP® docetaxel had significantly superior anti-cancer effects in vivo across a range of important cancer types when compared to Taxotere®. Breast, prostate, lung and ovarian tumour types were tested. In each case DEP® docetaxel was seen to significantly outperform the leading drug Taxotere®.
Starpharma's dendrimers improve efficacy of docetaxel in animals ( pdf file, 189kb)
Starpharma's docetaxel superior to Taxotere across multiple cancer types
( pdf file, 162kb)
Preventing neutropenia may allow more effective treatment and avoid the need for rescue therapy and hospitalisation
Neutropenia is the major dose-limiting toxicity for marketed formulations of docetaxel. Currently, rescue therapy for neutropenia can require expensive treatment with the growth factor G-CSF. G-CSF therapy still leaves the possibility of severe illness, hospitalisation or death from infection. In animal studies it has been found that DEP® docetaxel eliminates the neutropenia or thrombocytopenia caused by Taxotere® alone.
Starpharma Dendrimer-Docetaxel eliminates neutropenia ( pdf file, 152kb).
Elimination of polysorbate 80 reduces risk of anaphylactic reactions & may remove need for premedication with corticosteroids
Currently pre-treatment with corticosteroids is required before using Taxotere® or any marketed docetaxel formulation due to the inclusion of the surfactant polysorbate 80, which can lead to anaphylactic shock. Even with prophylaxis potentially fatal anaphylaxis can still occur.
The absence of surfactant in the DEP® docetaxel formulation may avoid the need for such prophylaxis, and avoid the risk of polysorbate 80 related anaphylactic fatalities.
DEP® docetaxel has been shown to preferentially accumulate in tumour tissues, with drug levels 40 times greater than are seen with conventional formulations of docetaxel. This is evidence of the significant tumour-targeting effect of Starpharma’s dendrimer formulation.
Starpharma's docetaxel demonstrates targeted tumour delivery ( pdf file, 365kb)
Extended drug half-life
In pre-clinical models DEP® docetaxel has a plasma half-life of between 40 to 60 hours, more than 40 times longer than for docetaxel alone. It is believed this is a contributing factor to the improved efficacy of DEP® docetaxel.
Wider Applications of the DEP® Dendrimer Drug Delivery platform
Starpharma applies its DEP® dendrimer drug delivery platform to its own pipeline, and in collaboration with a number of well known pharmaceutical companies.
DEP™ is applicable to small molecules, peptides, proteins and antibodies, yielding benefits such as efficacy, targeting, improved pharmacokinetics and reduced toxicity, as well as greatly increased aqueous solubility.
Applying DEP™ in this way has the potential to create innovative products with increased patient compliance and effectiveness and also provide companies with a unique market position leading to enhanced commercial returns.
DEP™ docetaxel is in Phase 1 clinical trials.
More information on the DEP™ platform is available here.
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