Magainin Pharmaceuticals Inc.'s topical cream for fighting infectionsin diabetic foot ulcers is as effective as the standard oral antibiotictreatment according to a preliminary analysis of data from the first oftwo Phase III trials of the drug, Cytolex.
The cream's active compound, derived from peptides that protect theskin of African clawed frogs from infection, also did not produce sideeffects, such as insomnia, associated with ofloxacin, the most widelyused antibiotic for diabetic foot ulcer infections.
Ofloxacin is marketed under the brand name Floxin by Ortho-McNeilPharmaceuticals, of Raritan, N.J., and typically is 70 percent to 95percent effective in combating infections.
In Magainin's two Phase III trials, Cytolex (MSI-78) is beingcompared with ofloxacin for clinical responses during 28 days oftreatment plus a follow-up period.
Cytolex achieved the primary endpoint _ defined as clinicalimprovement in or complete resolution of patients' infections _ anddemonstrated statistical equivalence with ofloxacin. Results from thesecond Phase III trial are expected in the first quarter of 1997.
The successful trial represents a resurgence for MSI-78, which failedto achieve statistical significance compared with a placebo in a 1994Phase III trial for impetigo. That study, however, demonstrated thedrug was safe.
Data from the Phase III diabetic foot ulcer trial were releasedWednesday and Magainin's stock (NASDAQ:MAGN) gained $1 toclose at $12.875. The company's shares Thursday lost $0.625,closing at $12.25, despite a move by Magainin, of PlymouthMeeting, Pa., to buyback royalty rights to Cytolex from HoughtenPharmaceuticals Inc., of San Diego.
In 1990, Richard Houghten, a founder of Houghten and its chieftechnical officer, developed analogues to the original anti-infectivepeptides, called magainins, which were discovered by MichaelZasloff, Magainin's scientific founder.
MSI-78 was one of the magainin derivatives created by Houghtenand licensed to Magainin Pharmaceuticals. HoughtenPharmaceuticals shared the license with The Scripps ResearchInstitute, of La Jolla, Calif.
Magainin Pharmaceuticals paid 550,000 shares of stock to buy backthe royalty rights. Houghten Pharmaceuticals and Scripps eachreceived 225,000 shares.
Michael Dougherty, Magainin's chief financial officer, said the dealensures greater revenues on the anticipated sale of Cytolex and givesthe company full ownership of the drug. Magainin, valuing the sharesat $12.90, said it will take a $7.1 million non-cash charge to earningsfor the stock swap.
If the second Phase III study is successful, Wall Street analystspredict Magainin could file a new drug application with the FDA bymid-1997 for Cytolex. The treatment, analysts estimate, will generateannual revenues of about $170 million a few years after it hits themarket.
Among the anticipated advantages of Cytolex over ofloxacin are theformer's lack of adverse side effects and its ability to kill pathogensthe latter cannot.
In the first Phase III trial, 584 patients were enrolled. Initially theywere divided into three groups: one receiving ofloxacin and the othertwo receiving either a 1 percent or 2 percent topical creamformulation. In June 1995, analysis of interim data showed Cytolexwas working at both doses, so patients using the 1 percent creamwere evaluated for comparison with ofloxacin. The 1 percent creamalso is the dose being used in the second Phase III trial. (SeeBioWorld Today, June 28, 1995, p. 1.)
In the Phase III trial reported this week, Roy Levitt, Magainin'sexecutive vice president and director of the company's newly formedInstitute for Molecule Medicine, said patient evaluations were madeperiodically during 28 days of treatment and in a follow-up period.
On day three of the treatment, Levitt said, clinical responses wereseen in 70 percent of patients. The percentage increased graduallyuntil the follow-up evaluation when nearly 90 percent of patientsreceiving Cytolex or ofloxacin showed clinical responses to thedrugs. Both drugs were well tolerated, but patients taking ofloxacincomplained of insomnia.
Levitt said more data on efficacy and side effects from the first PhaseIII trial will be presented when the second Phase III study results arecomplete.
He added the trials also will measure wound healing, but it is not anendpoint.
Levitt, a research scientist at Johns Hopkins University, joinedMagainin in January 1996 to establish an asthma program. Earlierthis year, the company said it found molecular targets from two genesbelieved to be regulators of allergic and inflammatory responsescharacteristic of asthma.
Levitt said his experience with asthma and other lung-relatedinflammatory disorders fits in well with Magainin's development ofanti-infective drugs to treat persistent infections, such as thoseassociated with cystic fibrosis. A magainin-derived peptidecompound is under study as a potential treatment for Pseudomonas incystic fibrosis patients.
Magainin has developed more than 2,000 derivatives of the naturalpeptides from which its name also is derived. Levitt said thecompany's expertise in peptide chemistry is being used to createsmall-molecule mimetics of proteins linked to asthma. n
-- Charles Craig
(c) 1997 American Health Consultants. All rights reserved.