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Immunogenicity Study Involving StaphVax in Cardiac Patients Meets Primary Endpoints of Safety and Immune Response
Patients undergoing various types of surgery, including cardiovascular surgery, are at increased risk of developing severe S. aureus infections. The risk is greatest during the immediate post-operative period while patients are still in the hospital and the next few weeks while recovering from surgery. This study was designed to provide evidence that a broader and generally healthier at-risk patient group, such as patients undergoing cardiovascular surgery, can achieve antibody levels equal to, or greater than, the protective antibody levels attained in immunocompromised end-stage renal disease (ESRD) patients in earlier clinical trials. In addition, the study was designed to assess safety and toleration of the vaccine in these patients.
The phase 2b immunogenicity study included a total of 120 patients from 15 cardiovascular surgery centers in the United States. This two-part, six-month study was double-blinded through the first six weeks following vaccination, when surgery patients are at greatest risk for post-surgical infections. Subjects were vaccinated prior to their cardiovascular procedure in order to assess their antibody levels during the period of greatest risk of S. aureus infection. While these patients were healthier than the ESRD patients studied in the Company's phase 3 efficacy trial, 25 percent were partially immunocompromised due to diabetes. Substantial increases in antibody levels were achieved in the vaccine recipients by day 7, and by day 14, the levels were far above the estimated protective antibody levels measured in compromised ESRD patients. On day 14, 93 percent of the patients had antibody levels above the estimated protective levels. This compares favorably to the 80-85 percent response rate observed in ESRD patients. The vaccine was very well tolerated. No serious adverse events were attributed to the vaccine. Reactions to the vaccine were generally mild and of short duration, similar to those experienced by ESRD patients. The second, unblinded phase of the study, which will provide more comprehensive assessment of the duration of vaccine effect in this population by following patients for up to six months, is still ongoing.
"These results support the potential to broaden the patient population beyond dialysis patients who can benefit from the protection afforded by StaphVAX against S. aureus. We expect to include these results in our 2005 Biologics License Application filing in the United States as well as a supplemental Marketing Authorization Application in Europe," stated Henrik S. Rasmussen, M.D., Ph.D., senior vice president, clinical, medical and regulatory affairs, Nabi Biopharmaceuticals. "This study is firmly aligned with our commercial growth strategy to build the industry's broadest and deepest Gram-positive bacterial infections franchise. We look forward to presenting the full dataset from this study at an upcoming scientific meeting, and as a full paper."
StaphVAX is currently in a confirmatory phase 3 trial designed to confirm that it can prevent S. aureus infections in ESRD patients. Patients with ESRD are at high risk of developing S. aureus bacterial infections and are among the most difficult patients to treat because they are immunocompromised due to their debilitating, underlying disease and because dialysis access provides an opportunity for bacteria to be introduced into their bloodstream. However, there are a large number of other patient populations who are at substantial risk for contracting S. aureus infections, such as patients undergoing cardiothoracic or orthopedic surgery, in particular when it involves implantation of prosthetic devices. It is estimated that there are a total of 12 million patients in the United States who are at risk of contracting these infections on an annual basis.
About S. aureus Infections
S. aureus is the most common cause of serious hospital-acquired bloodstream infections. Staphylococcal infections are difficult to treat because the bacteria, in most cases, is resistant to available antibiotics. This rise of antibiotic resistance has markedly curtailed options for treating S. aureus infections. According to the current estimates by the U.S. Centers for Disease Control and Prevention (CDC), more than two million patients in the United States each year contract an infection as a result of exposure to a pathogen while receiving care in a hospital. S. aureus can spread from the blood (bacteremia), to the bones (osteomyelitis), or the inner lining of the heart and its valves (endocarditis), or cause abscesses in internal organs such as the lungs, liver and kidneys. People most at risk for these infections are surgical patients, trauma or burn victims, newborns whose immune systems are not yet developed, and patients with chronic illnesses such as diabetes, cancer, or lung or kidney diseases. People whose immune systems are suppressed due to disease, chemotherapy, or radiation therapy are generally more susceptible to these bacterial infections.
About S. aureus Infections and Resistance Issues
An estimated 12 million patients are at risk for developing an S. aureus infection each year in the United States. In the country's 7,000 acute care hospitals, S. aureus is the leading cause of hospital-based bloodstream infections and has a crude mortality rate of 25 percent. The risk is highest for patients who are immunocompromised and for those who suffer from chronic debilitating illnesses, as well as for people treated with invasive devices such as a prosthetic or dialysis devices. S. aureus bacteria are becoming increasingly resistant to available antibiotics. It is estimated that over 95 percent of patients worldwide with S. aureus infections no longer respond to first-line antibiotics, such as penicillin or ampicillin. Methicillin is an alternative treatment, but nearly 60 percent of strains of S. aureus in the United States are now methicillin-resistant, and this number continues to rise. In other parts of the developed world, the rate of methicillin- resistant S. aureus incidence continues to grow, with resistance rates close to 80 percent in some Asian countries.
Source: Nabi Pharmaceuticals