CAL02 Treatment Could Be Breakthrough for Severe Pneumococcal Pneumonia

A recent study offers new hope in the fight against severe community-acquired pneumonia caused by Streptococcus pneumoniae, with evidence that a novel antitoxin agent called CAL02 helps patients fight these dangerous infections.

An estimated 900,000 Americans get pneumococcal pneumonia each year, according to the US Centers for Disease Control and Prevention (CDC). Further, the World Health Organization (WHO) has estimated that pneumococcal infections lead to 1.6 million deaths each year worldwide. Antibiotic resistance among strains of pneumococcus bacteria can lead to invasive pneumococcal disease, but a new study published in The Lancet Infectious Diseases indicates that an agent called CAL02 may be a valuable add-on therapy for patients with severe community-acquired pneumococcal pneumonia.

“CAL02 addresses the fundamental damages of severe community-acquired pneumonia,” said the study’s first author Pierre-François Laterre, MD, in a recent press release from Combioxin SA, the Swiss biotechnology company developing the drug. “Results published today in The Lancet Infectious Diseases provide a first set of evidence that targeting virulent effectors protects patients from organ dysfunction and has the potential to dramatically improve the outcome of patients in critical situations.”

According to the paper, CAL02 consists of liposomes engineered to capture and neutralize virulent bacterial toxins produced by pathogens such as Streptococcus pneumoniae, which often cause severe lung infections. Unlike antibiotics, CAL02 does not give rise to resistance, and can be administered alongside the antibiotics that patients receive for pneumonia.

To assess the safety of CAL02, investigators conducted a randomized, double-blind, multicenter, placebo-controlled trial in 10 intensive care units in France and Belgium, screening 280 patients from March 21, 2016, to January 13, 2018. A total of 19 patients were enrolled in the study, with 14 receiving CAL02—3 received low-dose CAL02 at 16 mg/kg and 11 received high-dose CAL02 at 4 mg/kg—and the remaining 5 patients placed in a safety group receiving a placebo. Of the 19 patients, 58% were in septic shock and 42% were under invasive mechanical ventilation during the treatment period.

The study team found that the drug was safe and that patients treated with CAL02 spent an average of 5 days in the intensive care unit, compared to an average of 12 days for patients in the placebo group. In addition, the patients receiving CAL02 had faster clinical improvement, including faster resolution of organ dysfunctions, as well was more rapid clearance of pneumonia. Investigators also found that CAL02-treated patients remained under invasive mechanical ventilation for an average of 4.5 days, as compared to 12 days for patients receiving standard of care without CAL02. Moreover, patients who received CAL02 had fully normalized and stable cardiovascular and hemodynamic status within 1 week while patients receiving placebo showed no improvement in the same period, and cure of pneumonia was more rapid with CAL02.

“Critical care costs represent a considerable percentage of overall health expenditures and hospital costs today,” said study co-author and Combioxin director Samareh Azeredo da Silveira Lajaunias, PhD. “By significantly reducing the length of stay in intensive care and by limiting the duration of mechanical ventilation, this treatment has the potential to lead to a tremendous economy on cost of care.”

The authors of an editorial accompanying the study echoed its promising results. “The advantages of CAL02 treatment were particularly obvious during the early course of the infection, when the bacterial load is high,” wrote the authors, calling the findings a medical breakthrough. “We keep our fingers crossed that CAL02 will not get lost on its way to the patients who need it.”