Magainin Pharmaceuticals Inc.'s broad-spectrum anti-infectivedrug MSI-78 was able to reduce the number of bacteria andfungi present in a skin infection by three to four orders ofmagnitude within one hour, according to results presented onMonday at the 33rd Interscience Conference on AntimicrobialAgents and Chemotherapy (ICAAC) in New Orleans.
Moreover, even the lowest dose (of 0.5 percent, or 75milligrams in a 15-gram tube) was able to sustain anti-microbial activity for at least six hours. And the highest dose(of 2 percent, or 300 milligrams per tube) was able to kill themicrobial flora for a full 24 hours.
MSI-78 is a synthetic magainin, a natural host-defense peptideisolated from frogs. Scientists at Magainin (NASDAQ:MAGN) ofPlymouth Meeting, Pa., altered the original molecule viachemical synthesis, though it still consists of natural aminoacids, explained Leonard Jacob, the company's executive vicepresident and chief operating officer.
The derivative is "highly potent," he said, yet retains theoriginal biological action of the native material. Magainins actby "punching holes selectively in the membranes of bacteriaand fungi," Jacob told BioWorld. "Because of this uniquemechanism, magainins have proven very active againstresistant microorganisms," he said.
The Phase II trial on 45 volunteers, which was completedearlier this year (and initiated in mid-January), was conductedby James Leyden, professor of dermatology at the University ofPennsylvania. Jacob presented the results at ICAAC.
The clinicians "inoculated" five sites on the forearms of thevolunteers with swabs from the perineum, which is known tobe a site dense with bacteria and fungi. They then occluded thetranslocation sites with plastic film for 24 hours.
"At the end of 24 hours there are about 10 million organisms (amixed culture) at each site," Jacobs explained. Then each sitereceived a single application of MSI-78 -- 0.5 percent, 1percent or 2 percent -- or vehicle alone. One site was left as anuntreated control. One hour later, all three doses of MSI-78 hadreduced the total number of aerobic organisms (which includescoagulase-negative staphylococci, Gram-positive rods andGram-negative bacteria) per site by three or four orders ofmagnitude: from 10 million to 1,000.
And after six hours of treatment with the compound, theresults were "just as good" for all three doses, Jacob toldBioWorld. Treatment reduced the total aerobe count to 100 to1,000 per site from 10 million per site. "This showed us notonly that the drug works quickly (which you would expect ifthe magainins work as a "detergent" and don't require thebacteria to be growing), but that it has sustained action," Jacobtold BioWorld.
"Even after 24 hours the antibiotic (the 2 percent solution) waspowerful enough to suppress the replication of bacteria," Jacobexplained. "The dose response difference in efficacy wasstatistically significant (p<0.05)," he added.
Magainin is currently conducting a Phase II/III trial on MSI-78in children suffering from the skin disease impetigo, which iscaused by staphylococci and streptococci, Jacob said. The onlyavailable treatment today is systemic antibiotic therapy, hesaid. The company has already enrolled 225 children in thetrial (which began in late June) and eventually intends to havedata from 250 evaluable patients.
In the Phase II/III trials, Magainin is again comparing thevehicle with the same three doses of MSI-78, applied topicallythree times a day for up to 12 days, Jacob told BioWorld. "Wewill be measuring clinical endpoints as well as a microbiologicalcure, and intend to complete the trial by year's end," he added.
-- Jennifer Van Brunt Senior Editor
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