Another Phase III trial is under way for MX-226, a topical antibiotic for local catheter-related infections that has been developed of late by Migenix Inc. in concert with Cadence Pharmaceuticals Inc.
The partners, who hope to duplicate previous Phase III data that reached statistical significance, began the multinational study's enrollment in the U.S., where it is being conducted under a special protocol assessment with the FDA. Their strategy reflects a shift relative to the peptide gel's indication, though, as that prior Phase III study missed statistical significance in its primary endpoint of reducing catheter-related bloodstream infections.
"The FDA agreed to allow us to use two secondary endpoints, one of which is the primary in this next confirmatory Phase III study to support an NDA," Jonathan Burke, Migenix's director of investor relations, told BioWorld Today. "So we're seeking a primary endpoint of statistically superior reduction in local catheter site infections in this particular Phase III, which we achieved with a high level of statistical significance in the previous Phase III study."
The compound, also known as CPI-226 (omiganan pentahydrochloride), is designed to kill organisms around catheter sites that can cause infection.
In the first Phase III study, which included more than 1,400 patents, the product reduced local catheter site infections by 49 percent (p=0.004) and catheter colonization by 21 percent (p=0.002) compared to the standard of care, povidone-iodine. But while those data were positive, they were not the trial's primary efficacy measure. In that regard, MBI-226 produced a 15 percent improvement in catheter-related bloodstream infections compared to povidone-iodine, but those results were not statistically significant, and Migenix's shares lost almost two-thirds of their value.
"The FDA agreed with us that in a well-controlled trial such as ours," Burke explained, "it would have required thousands and thousands of patients to get that statistical superiority demonstrated."
Back then, the Vancouver, British Columbia-based company was known as Micrologix Biotech Inc., and its partner was Fujisawa Healthcare Inc., of Deerfield, Ill. (See BioWorld Today, July 24, 2003.)
The latest Phase III trial is a randomized, evaluation committee-blinded study to compare MX-226's effectiveness to 10 percent povidone-iodine in preventing catheter-related infections in about 1,250 hospitalized patients with central venous catheters. The primary efficacy endpoint will measure the incidence of local catheter site infections, as Burke mentioned, while secondary objectives include assessing MX-226's ability to prevent catheter colonization and catheter-related bloodstream infections, as well as gathering additional safety data. He noted that local catheter site infections and colonization "are believed by many, according to the literature, to be surrogates to catheter-related bloodstream infections."
Should the second Phase III trial confirm those previous local infection results, Migenix and Cadence expect to move the fast-track product into the regulatory approval process in the U.S. and Europe, though both companies declined to estimate a timetable. Burke said the FDA would review data from both Phase III trials, with the coming findings designed to confirm initial local infection results, in making its eventual decision.
The North American and European territories are covered under their year-old agreement, through which Migenix licensed rights to Cadence in a deal totaling $32 million before a double-digit royalty on net sales. Also, they have formed a joint committee to oversee MX-226's development, though San Diego-based Cadence is responsible for manufacturing and clinical, regulatory and commercialization costs. No milestone payment is due as a result of the trial's start, as such compensation would come later upon regulatory filings, acceptance and approvals. When the agreement was signed, Cadence was known as Strata Pharmaceuticals Inc. (See BioWorld Today, Aug. 4, 2004.)
The partners expect MX-226 to be used to prevent infections related to central venous catheters and other percutaneous medical devices, including dialysis catheters and peripherally inserted central catheters. Sales of such products in 2003 were estimated to be 10.6 million units in the U.S. and 21.6 million globally. The companies projected those figures to grow to 14.7 million units in the U.S. in 2007, and 31.4 million around the world.
MX-226 is applied on the skin around a catheter's insertion site, prior to the first application of a dressing, as well as with subsequent dressing changes that take place every few days for the duration of catheterization. With an estimated three to four dressing changes per catheter, there could be about 58 million potential applications annually for MX-226 in the U.S. and more than 120 million globally by the time the product is launched.
Cadence is a specialty pharmaceutical company focused on developing and commercializing therapeutics for hospital settings, while Migenix is developing drugs for infectious and degenerative diseases. The latter's clinical pipeline includes a Phase II drug candidate called MX-3253 (celgosivir) for chronic hepatitis C infections, another Phase II product for acne and MX-4509 in Phase I for neurodegenerative conditions such as Alzheimer's disease. Its preclinical portfolio includes MX-2401 for the treatment of serious Gram-positive infections, MX-4565 for retinitis pigmentosa and MX-4042 for arthritis.
On Tuesday, Migenix's Canadian-listed shares (TSE:MGI) lost C1 cent to close at C39 cents (US33 cents). Its U.S.-listed stock (Pink Sheets:MGIFF) closed at 32 cents.