Hybrigenics today announced the positive outcomes of clinical tolerance Phase IIa study of daily oral inecalcitol in combination with gold standard Taxotere chemotherapy in hormone-refractory prostate cancer patients.
The maximal tolerated dose of inecalcitol is 4 milligrams (mg) per day and the response rate to combination treatment reached 85 per cent based on Prostate-Specific Antigen (PSA) decline within 3 months.
Given its excellent safety profile and strong presumption of efficacy, inecalcitol can proceed to clinical efficacy Phase IIb study in the same therapeutic indication. Other diseases such as hormone-dependent prostate cancer, severe psoriasis or hyperparathyroidism resulting from chronic kidney disease, are also being considered as additional indications of daily oral inecalcitol.
A total of 54 patients have been enrolled to test 9 dose levels from 40 micrograms up to 8 milligrams per day for a maximum of 18 weeks. Two patients receiving 8 mg per day experienced sustained grade 3 hypercalcemia after one or two weeks of administration.
Treatment was interrupted before any clinical symptom appeared. The maximal tolerated dose was established as 4 mg per day. Out of 52 patients treated up to 4 mg per day, 47 were evaluable by PSA monitoring and 40 patients showed more than 30 per cent decrease in PSA levels within three months: the final overall response rate of the study therefore reached 85 per cent. This figure compares favorably with the 65 per cent response rate observed with Taxotere alone in the studies having supported its registration in worldwide markets.
However, there was no direct comparison of Taxotere with or without inecalcitol in the present Phase IIa study and the difference between the two response rates should be interpreted as a strong presumption of efficacy, but not as a definitive proof. The main objective of the next Phase IIb study will be to bring this so-called clinical “proof-of-concept”.
The levels of parathyroid hormone (parathormone), a hormone involved in the physiological regulation of calcium levels, were markedly depressed by inecalcitol at the dose of 4 mg per day. There is a condition called “hyperparathyroidism” in which parathormone levels are increased as a result of chronic kidney disease. Other vitamin D analogues such as paricalcitol and doxercalciferol are already widely prescribed in this indication to normalize parathormone levels. This new observation at the maximal tolerated dose of inecalcitol opens another therapeutic field worth exploring.
Overall, the excellent safety profile of inecalcitol by the oral route now allows its use in diseases where tolerance criteria are more stringent than for hormone-refractory prostate cancer: hormone-dependent prostate cancer, hyperparathyroidism, and also severe psoriasis.
Inecalcitol is an orally active agonist targeting the vitamin D receptor. The therapeutic rationale behind its development is to add its cytostatic potential to the established efficacy of the reference treatments of the two stages of prostate cancer: anti-hormonals (LH-RH agonists and anti-androgens) for the hormone-dependent stage and Taxotere(R)-based chemotherapy for the hormone-refractory stage.
Hybrigenics
