In the study, the researchers produced data that include pharmacokinetic
characteristics consistent with prolonged circulation and controlled
drug release with plasma concentrations remaining up to at least
100-fold higher than conventional docetaxel for more than 24 hours, as
well as up to a 10-fold increase in intratumoral drug concentrations
with prolonged and enhanced tumor growth suppression in multiple tumor
models compared with conventional docetaxel.
Moreover, initial clinical data in a heavily pretreated patient
population with 17 patients with advanced or metastatic solid tumor
cancers indicated that BIND-014 displays pharmacological characteristics
consistent with preclinical findings of differentiated pharmacokinetics
and accumulation at tumor sites with clinical effects seen at doses as
low as 20 percent of the normally prescribed docetaxel dose and in
cancers in which docetaxel has minimal activity (e.g., cervical cancer).
development of BIND-014 demonstrates that drug properties such as
solubility, metabolism, plasma binding, biodistribution and target
tissue accumulation will no longer be constrained to the same extent by
the drug chemical composition. It will also become the function of the
physicochemical properties of nanoparticles. This will allow for an
unprecedented ability to make better medicines for our patients as
demonstrated by our emerging clinical data," said Farokhzad.
researchers note that while the science and technology of BIND-014
builds upon docetaxel's mechanism of action, the emerging evidence is
that BIND-014 significantly changes the biological effects of docetaxel
by virtue of fundamental changes in pharmacology including major
increases in tumor concentration.
To date, the researchers note
that BIND-014 has been administered at doses of up to 75 mg/m2 and dose
escalation is ongoing. It has been well-tolerated with no new toxicities