Bioniche Life Sciences Inc. hit a stumbling block in its efforts to secure FDA approval for Cystistat (sodium hyaluronate) after uncovering less-than-optimal results in a preliminary analysis of a late-stage trial.
The interstitial cystitis study missed its primary endpoint, as data showed that the Cystistat response rate was not statistically different from that of placebo. Bioniche had planned to include the data as part of a package to the FDA for product registration.
Judged on its own, though, Cystistat was more than 50 percent effective in eliciting a response, an endpoint defined by patient global satisfaction and pain reduction eight weeks into the Canadian- and U.S.-based studies. Treatment with the product, a device that delivers hyaluronic acid solution formulated for bladder instillation, lasted for six weeks followed by patient evaluations after eight, 12 and 16 weeks.
Belleville, Ontario-based Bioniche blamed the unforeseen finding on a higher-than-expected placebo response rate from the 138-patient, double-blinded, randomized, placebo-controlled trial.
"Interstitial cystitis is a complicated disease that is quite a challenge from a clinical point of view," Marc Riviere, Bioniche's senior vice president and chief medical officer, told BioWorld Today. "And even though the effect of the product is very acceptable, it's not different from placebo. The weird thing is that there is nothing in literature that would give a placebo response rate that high. It's two or three times what has been published."
He said the results intrigued the FDA as well, adding that different patient populations with the disease routinely respond differently to various therapies. Bioniche's program included patients 18 or older previously diagnosed with interstitial cystitis, as defined by the National Institute of Diabetes and Digestive and Kidney Diseases, a division of the National Institutes of Health in Bethesda, Md.
It will take another couple of months to complete a full analysis as Bioniche continues to dissect the latest data with investigators and regulatory authorities in the U.S. and Canada.
"Our next step is to complete the analysis and put those results, whatever they are, in perspective with data we already have and see whether the FDA thinks it's good enough or not," Riviere said.
He added that the company expected the latest findings to complement prior data reported at a number of recent scientific meetings, including the American Urology Association, the European Association of Urology and the American Society of Clinical Oncology conferences. Such previous findings pointed to the product's efficacy and tolerability, including statistically significant data showing that 71 percent of Cystistat-treated patients showed no symptoms after 12 weeks in a radiotherapy toxicity trial compared to 38 percent of standard-therapy patients.
"All that is part of what we wanted to submit to the FDA," Riviere said. "The outcome of the package will depend on what comes out of this specific trial. If we don't find any explanation, or if we can identify a factor and we can rework the results in an acceptable fashion for the regulatory agency, it could be part of the submission."
The product is marketed in more than 20 countries, including Canada and Europe, for the temporary replacement of the glycosaminoglycan layer of the bladder. Diseases that fall under the umbrella include interstitial and radiation-induced cystitis, recurrent bladder infections and catheter-induced infections. Bioniche is continuing European and Canadian trials of Cystistat for interstitial and other types of cystitis.
Elsewhere in its pipeline, Bioniche recently completed Phase II studies of a biological product for bladder cancer, a mycobacterial cell wall DNA complex. Another product, suplasyn, is an injectable device for osteoarthritis. The company also is researching a number of preclinical-stage oncology therapeutics.
Beyond its pharmaceutical and human health divisions, Bioniche develops products from its animal health and food safety divisions. Its stock (TSE:BNC) closed unchanged Monday at C$2.02.