BioWorld International Correspondent

Shares in BioXell SpA fell by 7.4 percent last week on news that the company's lead compound, the vitamin D3 analogue elocalcitol, missed its primary endpoint in a Phase II trial in non-bacterial chronic prostatitis.

According to results from the 129-patient study, there was no difference between treatment with the drug and placebo on the primary endpoint, a National Institutes of Health (NIH) questionnaire completed by participating patients that focused mainly on pelvic pain.

Following three months of treatment, both the placebo and the treatment arms of the study attained a 15-point reduction in the NIH/Chronic Pelvic Pain Syndrome (CPPS) symptom score. A full analysis of the data will be available Friday, but the Milan, Italy-based company already decided to discontinue further development of the compound in that indication.

However, several positive trends were observed, which, the company said, support its ongoing Phase II trials of elocalcitol in benign prostatic hyperplasia (BPH) and in overactive bladder (OAB)

Fifty-five percent of patients with a very high frequency of urination - greater than 10 times per day - attained a normal frequency following treatment with elocalcitol, whereas the equivalent statistic for the placebo group was just 14 percent. Those with a frequency of eight times per day also exhibited a reduction. A decrease in interleukin-8 levels in semen also was observed in the treatment group.

"We know now the drug does not work in pain," BioXell CEO Francesco Sinigaglia said on a conference call. "The positive point here is that we were able to see a reduction in lower urinary tract symptoms, confirming what we have previously seen in the overactive bladder trial and the BPH trial, plus some reduction on an important inflammatory biomarker, which, by the way, might open up additional potential indications for elocalcitol in inflammatory diseases."

The company is assessing the possibility of investigating elocalcitol's potential in several indications associated with elevated IL-8 levels, Sinigaglia said, including inflammatory bowel disease and chronic obstructive pulmonary disease.

The loss of the chronic prostatitis program was not a major setback, Nicolas Dunant, analyst at Zurich, Switzerland-based Bank am Bellevue told BioWorld International. "So far nothing has ever worked in this indication, so I was not very optimistic from the beginning," he said.

Bank am Bellevue acted as co-lead manager on BioXell's IPO on the Swiss Stock Exchange in Zurich, which netted the company €32.1 million (US$40.9 million). (See BioWorld International, Jun. 28, 2006.)

"When we did the valuation of the company, we valued only two projects: the BPH project and the OAB project," Dunant said. The prostatitis trial has "neither negative nor positive readthrough" to those other programs, he said, adding that the IL-8 observations are not hugely significant.

"Elocalcitol is clearly a drug with anti-inflammatory properties. I would expect it has some effect on interleukins and other molecules involved in inflammatory responses. [But] I only believe in the end in hard clinical outcomes," he said. "I would not pay too much attention to that for the time being."

Elocalcitol remains on track to complete enrollment in a 500-subject Phase IIb trial in BPH by year end, with results expected in the third quarter of 2007. A Phase IIb trial in OAB is slated to commence in early 2007.