2010 Intercell announced results from a Phase II clinical trial involving IC43, the vaccine candidate against infections with the bacterium Pseudomonas aeruginosa. The Phase II clinical trial met primary immunogenicity and safety end points and showed a significant reduction on mortality in the vaccine groups as compared to placebo.

In the randomized, placebo controlled Phase II clinical trial, mechanically ventilated intensive care patients were vaccinated. About 400 patients were enrolled in 33 intensive care units in 8 countries in Europe and Latin America.
No significant difference in Pseudomonas aeruginosa infection rates between any of the groups was apparent. However, this is likely to be due to the relatively small sample size of the current Phase II study. Larger, sufficiently powered clinical studies would be required to validate and verify any vaccine effects on mortality and infection rates.

In April 2011 Intercell announced that it has agreed with Novartis to advance Intercell's investigational Pseudomonas aeruginosa vaccine into a confirmatory clinical efficacy trial in ventilated ICU (Intensiv Care Unit) patients. The planned double blind study is powered to show a clinically meaningful and statistically significant reduction in overall mortality between the vaccine and control group and envisages enrolling about 800 subjects. Intercell will execute the trial and the costs will be shared with Novartis.

As another key objective, the Phase II trial investigated the feasibility of performing pivotal efficacy studies in this difficult target population: Final data confirm the anticipated number of Pseudomonas aeruginosa infections. These results confirm the development strategy for Intercells's Pseudomonas aeruginosa vaccine and could allow a pivotal assessment of the vaccine efficacy in potential future pivotal Phase III trials.

Intercell’s prophylactic vaccine against Pseudomonas infections has already shown safety and first hints of efficacy in former Phase II studies in patients with 2nd- and 3rd-degree burns.

Our vaccine candidate targeting Pseudomonas infections is being developed together with Novartis and is based on antigens derived from two outer-membrane proteins from Pseudomonas aeruginosa. Similar to previous trials, in Intercell's Phase II study the vaccine candidate has shown an excellent safety and tolerability profile. The vaccine was found to be highly immunogenic at all dose levels tested and has generated strong humoral responses even in patients with intensive care patients, who have a high risk of immune suppression. There were no critical safety findings.

A major cause of nosocomial infections

Pseudomonas aeruginosa (Pseudomonas) is the second-leading cause of nosocomial infections, which are mainly acquired in intensive care units, and affects primarily patients who require mechanical ventilation. Infections of the heart, central nervous system, respiratory system, skin and soft tissue are common. The free-living and tolerant gram-negative bacillus rarely causes infections in healthy persons but is a significant threat to patients suffering from cystic fibrosis or with a suppressed immune defense, particularly patients suffering from severe burns, cancer or HIV. Invasive infections may also occur when intact skin or mucous membrane is disrupted by insertion of medical devices as urinary or intravascular catheters.

Hospital-acquired infections are one of the major causes of death and serious illness worldwide, resulting in an annual cost burden of more than USD 20 billion in the developed world. In the United States and Europe about 6 million patients become infected annually resulting in 140,000 deaths per year. The incidence of nosocomial infections is steadily increasing due to increasing medical interventions and antibiotic resistance. 

Current treatment and prevention

Pseudomonas aeruginosa is intrinsically resistant to many antibiotics at concentrations achievable in vivo. In the treatment of pulmonary infection, antibiotics need to penetrate to the bronchial epithelium and secretions. However, in patients with cystic fibrosis and bronchiectasis, penetration may be reduced due to thickening and scarring of the bronchial wall.

Despite the use of newer broad-spectrum anti-Pseudomonas agents including cephalosporins, fluoroquinolones, and carbapenems, Pseudomonas aeruginosa infection remains a major cause of morbidity and mortality in hospitals. A variety of new approaches are under study including inhaled antibiotic therapy, growth factors and vaccines. Passive immunotherapeutic approaches using human monoclonal antibodies are also being investigated.

Currently there is no licensed vaccine available to prevent infection with Pseudomonas aeruginosa.

• In-house