Micrologix Biotech Inc.'s product designed to reduce the incidence of bacterial and fungal bloodstream infections related to the use of central venous catheters failed to hit its endpoint in a Phase III trial against povidone iodine, the standard of care, based on preliminary analyses.
The product, MBI 226, is a cationic peptide that Micrologix licensed from the University of British Columbia in 1993. Micrologix, of Vancouver, British Columbia, and partner, Fujisawa Healthcare Inc., of Deerfield, Ill., in July 2002 entered a deal potentially worth C$32 million (US$22.9 million) to Micrologix to develop MBI 226. (See BioWorld Today, July 10, 2002.)
David Friedland, Micrologix's vice president of clinical and medical affairs, told BioWorld Today that MBI 226 is supposed to prevent catheter colonization by killing bacteria on the skin, therefore preventing it from traveling down the outside of the catheter and seeping into the blood.
"We showed in the study that we could prevent catheter colonization [the study's secondary endpoint], and we would have expected to see a similar reduction or a bigger reduction in the bloodstream, but we didn't and we really don't know why," Friedland said. "We don't have all the data but when we get it, maybe we will be able to answer more questions."
The company's stock, which trades on the Toronto Stock Exchange (TSX:MBI), lost C82 cents Wednesday, or 63.1 percent, to close at C48 cents.
In the Phase III study, the rate of catheter-related bloodstream infections in the MBI 226 group was 2.2 percent compared with 2.6 percent in the povidone iodine group (p=0.966). A total of 1,452 patients enrolled in the trial and 1,392 people were evaluated.
On the secondary endpoint, MBI 226 did show statistically significant superiority in preventing catheter colonizations. The rate in patients with one or more colonized catheters was 31 percent in the MBI 226 group, compared with 40 percent in the povidone iodine group (p=0.002).
Friedland said catheter-related infections also might be caused by organisms traveling down the middle of the catheter or from different organs in the body. MBI 226 would not work in those areas, he said. Regarding whether either of those causes impacted the Phase III, Friedland said he wouldn't know until he reviewed all the data.
Micrologix initiated the Phase III trial in September 2000 after the FDA awarded MBI 226 fast-track status. Jim DeMesa, who was named Micrologix's president and CEO a year or so after the Phase III began, said the company initiated the trial on advice of the FDA following a small Phase II safety study of 261 patients and a Phase I study of 18 patients. Indeed, the Phase II did not include an efficacy element, he told BioWorld Today.
DeMesa said he's unsure when the final analysis will be complete. In accordance with the contract signed a year ago, Fujisawa owns the MBI 226 program in the indication and has the authority to make decisions about the next steps. While Fujisawa has 60 days to decide about terminating the agreement with Micrologix, DeMesa said it might take a little longer to go through the data.
Fujisawa spokeswoman Maribeth Landwehr told BioWorld Today company officials there also need time to go through the data before they can make any decisions about the future.
Since taking on the project, Fujisawa has invested between C$8 million to C$10 million in its development.
As for Micrologix, the company has about C$23 million in cash and a burn rate of C$15 million annually. DeMesa expects the burn rate to drop to about C$12 million a year later this year when the company completes its Phase IIb of MBI 594AN, a topical antibiotic for the treatment of acne.
The company also is studying MBI 1121, a topical antisense oligonucleotide drug in development for diseases associated with human papillomavirus. The product completed Phase I work in late 2001.
DeMesa doesn't anticipate reducing Micrologix's 55-person staff due to the missed trial. He said the company already has been operating with a lean staff and said most of the work connected with MBI 226 was being handled by Fujisawa.