Elocalcitol, a vitamin D3 analog for the potential treatment of benign prostatic hyperplasia, overactive bladder and male infertility.
Elocalcitol, which had been under development by BioXell SpA, is a synthetic derivative of vitamin D3 that regulates cell proliferation and apoptosis via its binding to the vitamin D receptor. In preclinical studies, elocalcitol inhibited the androgen-dependent and androgen-independent proliferation of benign prostatic hyperplasia (BPH) cells more potently than finasteride, a 5alpha-reductase inhibitor. In a phase IIb trial in patients with BPH, treatment with elocalcitol resulted in a significantly reduced prostate volume compared with placebo; irritative urinary symptoms (frequency, urgency and nocturia) and urodynamic parameters were comparable to the alpha1-adrenoceptor antagonist tamsulosin. In a phase IIa trial in patients with prostatitis, elocalcitol significantly reduced levels of IL-8 in semen, suggesting improved quality and forward motility of sperm. However, phase IIb trial data from patients with overactive bladder (OAB) were less promising: elocalcitol failed to meet the primary endpoint despite demonstrating good efficacy in a phase IIa trial. Based largely on these disappointing data, BioXell decided to terminate all further clinical development of elocalcitol, including an uncompleted phase IIa trial in patients with male infertility. Given the novel mechanism of action, efficacy profile and improved tolerability of elocalcitol over existing classes of drugs, the compound could have potentially added to the armamentarium in the expanding therapeutic markets of BPH, OAB and male infertility. This possibility appears to have been negated by BioXell's recent decision to terminate all further development of elocalcitol.
Tiwari
Atul
A
Jubilant Biosys Ltd, Drug Discovery Unit, #96, 2nd Stage, Industrial Suburb Yeshwantpur, Bangalore, India. atul_tiwari@jubilantbiosys.com
D000818:Animals; D006801:Humans; D008297:Male; D017209:Apoptosis / Q000187:drug effects; D002117:Calcitriol / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D017322:Clinical Trials, Phase II as Topic; D007248:Infertility, Male / Q000188:drug therapy / Q000503:physiopathology; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000503:physiopathology; D018167:Receptors, Calcitriol / Q000187:drug effects / Q000378:metabolism; D053201:Urinary Bladder, Overactive / Q000188:drug therapy / Q000503:physiopathology
C487049:BXL628; D002117:Calcitriol; D018167:Receptors, Calcitriol