BioWorld International Correspondent

Italian biopharmaceutical firm BioXell SpA has commenced recruitment for a Phase II clinical trial of its vitamin D3 analogue BXL-628, which it is developing as a treatment for benign prostatic hyperplasia (BPH). The double-blind, randomized, placebo-controlled study will involve 120 patients at 12 centers in Italy.

"The primary endpoint is reduction in prostatic volume measured by MRI," BioXell Chief Medical Officer Enrico Colli told BioWorld International. The secondary endpoints are based on measures of symptom severity and urinary flow rate. The molecule was well tolerated in a Phase I clinical trial, he said. "We have not seen hypercalcemia [elevated calcium levels], even at the top dose in the Phase I."

Milan-based BioXell aims to achieve a similar level efficacy to that of Proscar (finasteride), marketed by Merck & Co. Inc., of Whitehouse Station, N.J., but without the accompanying loss of sexual function that can occur. "We think it's a novel mechanism of action. If the drug works, we can get a very favorable position in the market," Colli said.

BPH, a benign enlargement of the prostate gland that interferes in urinary function, develops in approximately 50 percent of men older than 60, according to BioXell. Proscar works by inhibiting the enzyme 5-alpha reductase, which catalyzes the conversion of testosterone to dihydrotestosterone, an androgen that stimulates prostate growth. BXL-628 is a vitamin D3 agonist. It binds to and activates vitamin D receptors, which then trigger an array of growth-related effects.

BioXell Chief Scientific Officer Luciano Adorini said its presumed mechanisms of action include blocking of cell-cycle progression, an effect that is common to vitamin D3 analogues, and a decrease in the level of expression of the anti-apoptotic gene BCL-2. "The net effect is increased apoptosis, even in the presence of growth factors," he said.

In addition, he said, BPH increasingly is being viewed as an inflammatory condition as well as a hyperplasia, and vitamin D3 analogues - commonly used to treat psoriasis - are known to have anti-inflammatory effects. "This may be another interesting mechanism of action, which could play a role in BPH, we hope," Adorini said.

BioXell also is investigating BXL-628 as a potential supplement to immunosuppression therapy in graft rejection, and is planning to initiate a Phase II clinical trial in the U.S. "We have examined it in models of acute and chronic rejection in mice and found it to be very active," Adorini said. As well as acting on dendritic cells and T cells, it can also counter vascular problems due to epithelial and smooth muscle cell proliferation following transplantation.