This pharmaceutical optimisation follows the demonstration of safety and the presumption of efficacy of oral doses as high as 4mg of inecalcitol per day in a Phase IIa clinical tolerance study in hormone-refractory prostate cancer patients.
Microdosed vitamin D analogues are currently marketed as oily solutions in soft gelatin capsules. The first formulations of inecalcitol were also soft gel capsules of different increasing concentrations and strengths, up to a maximum of 1mg unit dose. Patients treated at the highest tolerated dose had to swallow four such capsules.
The new capsules are more concentrated in inecalcitol and contain a fixed 2mg amount. Hybrigenics says treatment will therefore be more convenient with a maximum of two small capsules to swallow, which also favours compliance.
Inecalcitol has also been formulated as 2mg scored tablets, which provides the flexibility to adjust doses 1mg by 1mg. Drinking solutions of inecalcitol in a liquid excipient could provide complete dose proportionality to body weight, for paediatric indications for example.
Hybrigenics says pharmaceutical stability and human bioavailability studies in healthy volunteers are ongoing. It aims to start Phase IIb efficacy clinical trials in hormone-refractory prostate cancer and severe psoriasis with a formulation suitable for future commercialisation.
‘We have worked hard to reduce the size of soft gel capsules and to make tablets feasible, against all odds,’ said Rémi Delansorne, chief executive of Hybrigenics.
‘The new formulations are smaller, cheaper, more convenient and flexible to use. Moreover, we believe they are novel and inventive for a vitamin D analogue such as inecalcitol, potentially paving the road for patent protection until 2030.’
