Cepheid, Sunnyvale, Calif, will collaborate with MedImmune, Gaithersburg, Md, and Combating Bacterial Resistance in Europe (COMBACTE), a public-private partnership set up by the European Union’s Innovative Medicines Initiative, to develop a series of rapid diagnostic tests to identify Staphylococcus aureus and Pseudomonas aeruginosa in respiratory secretions of mechanically ventilated patients.
The tests will be used to help identify patients for MedImmune’s MEDI4893 and MEDI3902 clinical programs, which are being conducted within the COMBACTE consortium to explore the use of biologics in preventing ventilator-associated pneumonia (VAP) infections in intensive-care-unit (ICU) patients.
MEDI4893 is a novel monoclonal antibody that targets alpha toxin produced by S. aureus and is currently being investigated by MedImmune and COMBACTE for the prevention of nosocomial pneumonia caused by S. aureus. MEDI3902 is a bispecific antibody under investigation for the prevention of nosocomial pneumonia caused by P. aeruginosa, a highly drug-resistant bacterium. Xpert tests from Cepheid are expected to help identify patients colonized with S. aureus or P. aeruginosa before they have clinical signs of pneumonia, so that these patients can be enrolled in the respective MEDI4893 or MEDI3902 clinical trials.
“Utilizing rapid diagnostics is a key component in effectively targeting serious healthcare-associated pathogens in our MEDI4893 and MEDI3902 clinical trials,” says Steve Projan, head of infectious diseases and vaccines for the innovative medicines unit at MedImmune. “We believe that the combination of rapid diagnostics and pathogen-specific antibodies will help physicians identify patients at risk and prevent serious and life-threatening infections in a way that is not possible today. By developing diagnostic tests through this collaboration with Cepheid, we can ensure that novel life-saving antibodies are delivered to patients who need them in a rapid and efficient manner.”
As part of the collaboration, Cepheid has adapted its existing Xpert MRSA/SA skin and soft tissue infection test cartridge for use with respiratory samples for the detection of patients with respiratory colonization with S. aureus and methicillin-resistant Staphylococcus aureus (MRSA). In addition, Cepheid has developed a new Xpert test cartridge to support the rapid identification of patients colonized with P. aeruginosa for patient enrollment in clinical trials for MEDI3902 starting early in 2016.
“Cepheid is pleased to be working with MedImmune and COMBACTE to address the critical challenges posed by serious bacterial infections. We believe this can be achieved through the use of molecular diagnostic tests to precisely target colonized patients, improve clinical trial efficiency, and accelerate these much needed therapeutics to market,” says John Bishop, chairman and CEO of Cepheid. “These two initial projects give Cepheid an opportunity to demonstrate its technology leadership, while also building an installed base of GeneXpert systems that could be leveraged for future COMBACTE or broader Innovative Medicines Initiative programs.”
MedImmune has FDA “fast track” designation for both MEDI4893 and MEDI3902.
The MEDI4893 Phase II trial is the first interventional trial ever designed and executed within COMBACTE. It also represents a paradigm shift in the infectious disease field, studying a preemptive approach using a monoclonal antibody to help prevent VAP and nosocomial pneumonia due to S. aureus. A total of 462 patients are expected to be enrolled in this study across approximately 80 sites in Europe.
The MEDI3902 molecule is currently in a Phase I trial and a Phase II trial is anticipated to start in the first quarter of 2016.
“We are pleased that COMBACTE is supporting the implementation, training and validation of both the S. aureus and P. aeruginosa screening tests,” says Herman Goossens, MD, head of COMBACTE’s laboratory network and an investigator in both the MEDI4893 and MEDI3902 trials. “Our ability to engage the laboratories in the network will ensure timely implementation and standardization of the platform while allowing us to determine the utility of identifying colonized patients before they show clinical signs of pneumonia.”
According to the US Centers for Disease Control and Prevention, S. aureus and P. aeruginosa together account for more than 40% of VAP infections in the United States.1 The length of stay in the ICU is extended on average 17 days after pneumonia onset when either S. aureus or P. aeruginosa are present, and the attributable mortality can reach 30% despite the use of currently available antibiotics.
- Sievert DM, Ricks P, Edwards JR, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009–2010. Infect Control Hosp Epidemiol. 2013;34(1):1–14; doi: 10.1086/668770.