AMBI DRUG CANDIDATE ERADICATES ANTIBIOTIC-RESISTANT "STAPH" BACTERIA IN STUDY OF INFECTED HEART VALVES
Lysostaphin Superior to Vancomycin in Animal Study
"Staph" Infections Occur in Approximately 500,000 US Patients Annually
Tarrytown, New York, September 29, 1997 -- AMBI Inc. (Nasdaq: AMBI) announced results of a preclinical study demonstrating that lysostaphin, the CompanyÃs proprietary antibacterial agent, was used successfully to treat endocarditis caused by methicillin-resistant Staphylococcus aureus (MRSA) bacteria. Lysostaphin completely eradicated the bacteria in more than 90 percent of the animals, whereas vancomycin, the current treatment of choice for this infection, did not eradicate the bacteria in any of the animals in this study.
The experiment used a rabbit model that closely mimics endocarditis disease in humans, and was performed under the supervision of Gordon Archer, MD, Chairman, Division of Infectious Diseases, Department of Internal Medicine and Professor of Medicine and Microbiology/Immunology, Virginia Commonwealth University, the Medical College of Virginia, and Michael Climo, MD, Assistant Professor of Medicine, Virginia Commonwealth University and the McGuire Veterans Administration Hospital. Dr. Archer presented the results of this study at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Toronto, Canada.
Dr. Archer said, "The unprecedented success with lysostaphin suggests that this novel agent has the potential to eradicate the bacterial infection more rapidly than currently available therapeutic agents, thus preventing the extensive valve destruction that may lead to cardiac surgery."
Richard Novick, MD, Professor of Microbiology and Medicine, Skirball Institute, New York University School of Medicine, and a member of AMBIÃs Scientific Advisory Board said, "There is widespread concern that infections with Staphylococcus aureus will resist all available antibiotics. The recent discovery of vancomycin resistance in clinical isolates of Staphylococcus aureus in Japan and the United States makes the promise of lysostaphin therapy very timely. Vancomycin is known as the drug of last resort, but with the increasing resistance to it, new agents are necessary to prevent bacteria from gaining the upper hand in the war against infectious disease."
Lysostaphin is an enzyme that is being developed by AMBI for the treatment of serious infections caused by drug-resistant Staphylococcus aureus (S. aureus), including endocarditis. Staphylococcal infections occur in approximately 500,000 patients each year in the US. The mortality rate from infectious endocarditis caused by S. aureus is approximately 30 percent, and about half of the patients require risky surgery to replace infected heart valves damaged by the bacteria.
Lysostaphin kills S. aureus by acting as an "enzymatic scalpel" that precisely cuts the very structures within the bacterial cell wall that are necessary for its structural strength, much as a surgeonÃs scalpel produces maximum benefit with a minimum of precise cutting.
In Dr. ArcherÃs study, lysostaphin given intravenously three times daily at a dose of 5 mg/kg completely eradicated infection in 10 of 11 animals treated for three days. In contrast, when vancomycin was given intravenously twice daily at a dose of 30 mg/kg -- a regimen found to be optimum for the drug -- there was a reduction of the number of bacteria infecting the animals, but infection was not eradicated in any of the 15 animals treated.
Solomon Mowshowitz, Ph.D., Vice President, Research and Development of AMBI commented, "Dr. ArcherÃs findings confirm and extend earlier studies of AMBI scientists which demonstrated that lysostaphin could be used effectively to cure lethal, systemic S. aureus infections in animals. When mice were challenged intraperitoneally with S. aureus, a single dose of lysostaphin at 0.16 mg/kg given intravenously -- a very low dose compared to what is given for traditional antibiotics -- cured all of the animals. Nevertheless, we did not anticipate that lysostaphin would be so effective in curing endocarditis, which is among the most clinically challenging infections caused by this virulent organism."
AMBI indicated that it will seek a corporate partner to co-develop and commercialize lysostaphin as a potential treatment for serious infections with drug-resistant S. aureus. In addition, it noted that a US patent has been issued on the cloned lysostaphin gene and that three other patents on lysostaphin technology have been issued.
Lysostaphin joins the lanthocin class of peptides as part of AMBIÃs armamentarium of disease-fighting technologies being developed for the treatment of antibiotic-resistant infections. Nisin, the CompanyÃs lead lanthocin drug candidate, is being developed both as an oral and as an injectable treatment for a variety of bacterial infections. Unlike lysostaphin, an enzyme that acts like a scalpel to destroy bridges that support bacterial cell walls, nisin is a peptide that acts like a bullet to break through and destroy bacterial cell membranes.
Infective endocarditis is a general term for an inflammation of the heart lining and valves caused by various bacteria. The most common risk factors are degenerative heart disease, valve deformities, and the presence of prosthetic heart valves or other types of intravascular devices. Intravenous drug use is also a major risk factor, accounting for 25 percent of all cases. However, S. aureus can cause infective endocarditis even in a completely healthy heart.
Treatment often involves surgical removal of the valve in addition to prolonged usage of antibacterial agents (typically of 4-6 weeks duration), particularly in the case of staphylococcal infections. For treatment of serious infections with MRSA, the only antibiotic presently available is vancomycin, which is becoming less effective as resistant organisms emerge.
AMBI develops pharmaceuticals for serious infectious diseases, and develops and commercializes nutrition products for cardiovascular and other conditions.
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Preliminary results in the lysostaphin development program are encouraging. However, it is important to note that the development of lysostaphin as a therapeutic agent for bacterial infections can be a long, difficult, and expensive process. Notwithstanding any favorable outcomes reported herein, there can be no assurance that a lysostaphin product will be approved by the FDA or its regulatory equivalent in a foreign country.
The statements in this press release that are not historical facts are forward-looking statements based upon current expectations. Such forward-looking statements involve risks and uncertainties, the regulation of AMBIÃs business generally and the other risks and uncertainties set forth in "Risk Factors" and elsewhere in AMBIÃs Registration Statement on Form S-3 and the Prospectus dated June 18, 1996 constituting a part thereof and Form 10-Q for the quarter ended March 31, 1997. Actual results and timing of certain events could differ materially from those indicated in the forward-looking statements as a result of these and other factors.
Contacts:
Dian Griesel, PhD, The Investor Relations Group
(212) 664-8489
AMBI Investor Relations
(914) 345-6888
Todd Appleman, Burson-Marsteller
(310) 226-3042
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