ICAAC: ZYVOX Effective Against Gram-Positive Bacteria
SAN FRANCISCO, CA. -- September 27, 1999 -- Preliminary results from several, large Phase III clinical trials coupled with Phase II data suggest that ZYVOX™ (linezolid), an investigational new antibiotic under development by Pharmacia & Upjohn (NYSE: PNU), is effective for the treatment of infections caused by Gram-positive bacteria in both adults and children.
These data were discussed at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) as well as during symposia titled "Strategies for Successful Treatment of Gram-Positive Bacterial Infections and New and Emerging Therapies."
Worldwide, more than half of the infections treated in a hospital involve Gram-positive bacteria. ZYVOX is the first of a new class of antibiotics being developed and studied for the treatment of these infections such as hospital and community-acquired pneumonia, skin and soft tissue infections and associated blood stream infections, known as bacteremia. Studies completed to date show that linezolid, the active ingredient in ZYVOX, is active in vitro against medically significant Gram-positive bacteria, such as staphylococci, streptococci and enterococci, including those bacteria resistant to other antibiotics.
In a preliminary analysis of a Phase III clinical trial involving 397 patients with hospital-acquired pneumonia (HAP), IV ZYVOX plus aztreonam showed a 66.4 percent clinical success rate. Results for ZYVOX were equivalent to the active comparator, IV vancomycin plus aztreonam, which showed a clinical success rate of 68.1 percent. The primary objective of this Phase III clinical trial was to demonstrate equivalence between ZYVOX and the comparator treatment.
In a preliminary analysis of a community-acquired pneumonia (CAP) Phase III clinical trial involving 526 evaluable hospitalized patients, IV to oral ZYVOX (patients were started on IV therapy and could be changed to oral therapy during the study) showed a clinical success rate of 90.8 percent. Results for ZYVOX were equivalent to an active comparator regimen, IV ceftriaxone followed by oral cefpodoxime, which showed a clinical success rate of 88.6 percent. A subset of this population (53 evaluable patients) was also treated for associated bacteremia. In these cases, ZYVOX demonstrated a clinical success rate of 93.3 percent while an active comparator, IV ceftriaxone followed by oral cefpodoxime, showed a clinical success rate of 69.9 percent.
In a separate CAP Phase III clinical trial involving 407 evaluable patients, oral ZYVOX showed an 89.6 percent clinical success rate. Results for ZYVOX were equivalent to the active comparator, oral cefpodoxime, which showed a clinical success rate of 90.8 percent.
A preliminary analysis of a Phase III clinical trial for complicated skin and soft tissue infections involving 591 evaluable patients found IV to oral ZYVOX showed a clinical success rate of 90.7 percent. Results for ZYVOX were equivalent to the active comparator, IV oxacillin/oral dicloxacillin, which showed a clinical success rate of 86.3 percent. In a preliminary analysis of a Phase III clinical trial for uncomplicated skin and soft tissue infections involving 611 evaluable patients, oral ZYVOX showed a clinical success rate of 91.3 percent. Results for ZYVOX were equivalent to the active comparator, oral clarithromycin, which showed a clinical success rate of 87.0 percent.
The primary objective of the CAP, bacteremia and skin and soft tissue Phase III clinical trials was to demonstrate equivalence between ZYVOX and the comparator treatments.
Two additional Phase III clinical trials assessing the activity of ZYVOX against some of today's most problematic Gram-positive bacteria were discussed at ICAAC. In a preliminary analysis of a study of ZYVOX for the treatment of infections caused by methicillin-resistant staphylococcal strains (MRSS), ZYVOX showed a clinical success rate of 77 percent. These results were equivalent to an active comparator, IV vancomycin, which showed a clinical success rate of 74.4 percent. Preliminary results from a Phase III clinical trial involving 145 patients with infections caused by vancomycin-resistant Enterococcus (VRE) were described. These trials compare the efficacy of two dose levels of ZYVOX in treating these infections because no other treatment option is approved for use as a treatment for VRE infections. ZYVOX in a 600 mg dose every 12 hours showed an 88.6 percent clinical success rate while ZYVOX in a 200 mg dose every 12 hours showed a 73.7 percent success rate. The VRE study demonstrated that the 600 mg dose of ZYVOX was significantly more effective than the 200 mg dose.
Data from a Phase II, open-label, uncontrolled clinical trial on the treatment of children 12 months to 6 years of age with CAP also were discussed. In this study, ZYVOX showed a 95.3 percent clinical success rate. The most common drug-related medical events reported for ZYVOX in the Phase II clinical trials were headache, nausea and diarrhea that were usually mild to moderate in intensity.
"In hospitals around the globe, we are facing difficult-to-treat infections caused by Gram-positive bacteria," said George Eliopoulos, MD, Associate Professor of Medicine, Harvard Medical School, Director, Office of House Staff Affairs, Beth Israel Deaconess Medical Center, Boston, Massachusetts. "These infections are seen in hospitalized patients with pneumonia or aggressive skin infections in patients with burns or wound infections that may develop following a surgical procedure. These experiences in clinical studies suggest that ZYVOX will become a useful alternative in these challenging cases."
Gram-positive pathogens are currently defined by many in the public health and infectious disease communities as the greatest challenge in hospital infections. ZYVOX is the first drug from the new oxazolidinone class developed for clinical use, the first new antibiotic with a novel mechanism of action in more than 35 years. Linezolid, the active ingredient in ZYVOX, blocks bacterial growth in an entirely new way by disrupting the initiation of bacterial protein synthesis.
ZYVOX has been developed in both IV and oral formulations. The oral formulation is 100-percent bioavailable, meaning no dose adjustment was necessary when switching from IV to oral dosing in clinical trials.
ZYVOX is in late stage clinical trials and Pharmacia & Upjohn plans to submit a New Drug Application (NDA) for ZYVOX to the FDA and other regulatory authorities around the world by the end of 1999.
These data were discussed at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) as well as during symposia titled "Strategies for Successful Treatment of Gram-Positive Bacterial Infections and New and Emerging Therapies."
Worldwide, more than half of the infections treated in a hospital involve Gram-positive bacteria. ZYVOX is the first of a new class of antibiotics being developed and studied for the treatment of these infections such as hospital and community-acquired pneumonia, skin and soft tissue infections and associated blood stream infections, known as bacteremia. Studies completed to date show that linezolid, the active ingredient in ZYVOX, is active in vitro against medically significant Gram-positive bacteria, such as staphylococci, streptococci and enterococci, including those bacteria resistant to other antibiotics.
In a preliminary analysis of a Phase III clinical trial involving 397 patients with hospital-acquired pneumonia (HAP), IV ZYVOX plus aztreonam showed a 66.4 percent clinical success rate. Results for ZYVOX were equivalent to the active comparator, IV vancomycin plus aztreonam, which showed a clinical success rate of 68.1 percent. The primary objective of this Phase III clinical trial was to demonstrate equivalence between ZYVOX and the comparator treatment.
In a preliminary analysis of a community-acquired pneumonia (CAP) Phase III clinical trial involving 526 evaluable hospitalized patients, IV to oral ZYVOX (patients were started on IV therapy and could be changed to oral therapy during the study) showed a clinical success rate of 90.8 percent. Results for ZYVOX were equivalent to an active comparator regimen, IV ceftriaxone followed by oral cefpodoxime, which showed a clinical success rate of 88.6 percent. A subset of this population (53 evaluable patients) was also treated for associated bacteremia. In these cases, ZYVOX demonstrated a clinical success rate of 93.3 percent while an active comparator, IV ceftriaxone followed by oral cefpodoxime, showed a clinical success rate of 69.9 percent.
In a separate CAP Phase III clinical trial involving 407 evaluable patients, oral ZYVOX showed an 89.6 percent clinical success rate. Results for ZYVOX were equivalent to the active comparator, oral cefpodoxime, which showed a clinical success rate of 90.8 percent.
A preliminary analysis of a Phase III clinical trial for complicated skin and soft tissue infections involving 591 evaluable patients found IV to oral ZYVOX showed a clinical success rate of 90.7 percent. Results for ZYVOX were equivalent to the active comparator, IV oxacillin/oral dicloxacillin, which showed a clinical success rate of 86.3 percent. In a preliminary analysis of a Phase III clinical trial for uncomplicated skin and soft tissue infections involving 611 evaluable patients, oral ZYVOX showed a clinical success rate of 91.3 percent. Results for ZYVOX were equivalent to the active comparator, oral clarithromycin, which showed a clinical success rate of 87.0 percent.
The primary objective of the CAP, bacteremia and skin and soft tissue Phase III clinical trials was to demonstrate equivalence between ZYVOX and the comparator treatments.
Two additional Phase III clinical trials assessing the activity of ZYVOX against some of today's most problematic Gram-positive bacteria were discussed at ICAAC. In a preliminary analysis of a study of ZYVOX for the treatment of infections caused by methicillin-resistant staphylococcal strains (MRSS), ZYVOX showed a clinical success rate of 77 percent. These results were equivalent to an active comparator, IV vancomycin, which showed a clinical success rate of 74.4 percent. Preliminary results from a Phase III clinical trial involving 145 patients with infections caused by vancomycin-resistant Enterococcus (VRE) were described. These trials compare the efficacy of two dose levels of ZYVOX in treating these infections because no other treatment option is approved for use as a treatment for VRE infections. ZYVOX in a 600 mg dose every 12 hours showed an 88.6 percent clinical success rate while ZYVOX in a 200 mg dose every 12 hours showed a 73.7 percent success rate. The VRE study demonstrated that the 600 mg dose of ZYVOX was significantly more effective than the 200 mg dose.
Data from a Phase II, open-label, uncontrolled clinical trial on the treatment of children 12 months to 6 years of age with CAP also were discussed. In this study, ZYVOX showed a 95.3 percent clinical success rate. The most common drug-related medical events reported for ZYVOX in the Phase II clinical trials were headache, nausea and diarrhea that were usually mild to moderate in intensity.
"In hospitals around the globe, we are facing difficult-to-treat infections caused by Gram-positive bacteria," said George Eliopoulos, MD, Associate Professor of Medicine, Harvard Medical School, Director, Office of House Staff Affairs, Beth Israel Deaconess Medical Center, Boston, Massachusetts. "These infections are seen in hospitalized patients with pneumonia or aggressive skin infections in patients with burns or wound infections that may develop following a surgical procedure. These experiences in clinical studies suggest that ZYVOX will become a useful alternative in these challenging cases."
Gram-positive pathogens are currently defined by many in the public health and infectious disease communities as the greatest challenge in hospital infections. ZYVOX is the first drug from the new oxazolidinone class developed for clinical use, the first new antibiotic with a novel mechanism of action in more than 35 years. Linezolid, the active ingredient in ZYVOX, blocks bacterial growth in an entirely new way by disrupting the initiation of bacterial protein synthesis.
ZYVOX has been developed in both IV and oral formulations. The oral formulation is 100-percent bioavailable, meaning no dose adjustment was necessary when switching from IV to oral dosing in clinical trials.
ZYVOX is in late stage clinical trials and Pharmacia & Upjohn plans to submit a New Drug Application (NDA) for ZYVOX to the FDA and other regulatory authorities around the world by the end of 1999.