AT ASM MICROBE 2017

NEW ORLEANS (FRONTLINE MEDICAL NEWS) – Monoclonal antibody therapies have already upended treatment strategies in cancer, dermatology, and multiple inflammatory diseases, and infectious disease may be next.

That’s because a single injection of a monoclonal antibody in development, AR-301, appeared to be safe and effective as an adjunct treatment for severe pneumonia caused by Staphylococcus aureus , according to a new study. The monoclonal antibody attacks the alpha-toxin secreted by S. aureus, thereby helping to protect immune cells.

Researchers assessed 48 patients between May 2012 and May 2016 in a randomized, double-blind, placebo-controlled trial. Each participant received a single injection of placebo or AR-301 (at one of four doses) to test the antibody’s tolerability and effectiveness.

“We know S. aureus pneumonia is a big problem. There is a lot of antibiotic resistance, and that is why we need new treatments,” Celine Gonzalez, MD, of the Dupuytren Central University Hospital in Limoges, France, said in an interview.

“Animal studies have shown the monoclonal antibody seems to be useful. This is the first in-human study to use a monoclonal antibody to treat hospital-acquired pneumonia due to Staphylococcus aureus,” Dr. Gonzalez said in a late-breaking poster presentation at the annual meeting of the American Society for Microbiology.

Treatment started within 36 hours of onset of severe pneumonia. Severity was based on a mean PaO2/FiO2 of 147 and/or a need for catecholamine. Six cases of pneumonia were related to MRSA and the remaining 42 to methicillin-susceptible S. aureus. The mean APACHE II score was 18.7, the mean Clinical Pulmonary Infection Score was 9.6, and the mean Sequential Organ Failure Assessment score was 6.9.

Participants were recruited from 13 ICUs in four countries. About 80% of participants were men. Their mean age was 56 years, and mean body mass index was 29 kg/m2. Concurrent antibiotic treatment choice and duration were at the investigator’s discretion.

S. aureus infection was considered eradicated if a follow-up culture was negative, a result achieved by 63% of the 16 placebo patients and 75%-88% of the AR-301-dosage groups. Eradication was also based on observed clinical success in the absence of a confirmatory culture. This was achieved by 38% in the placebo group and 13%-25% of the monoclonal antibody cohorts. A total of seven placebo patients and 15 AR-301 patients met eradication by these criteria.

Side effects were primarily minor and transient, Dr. Gonzalez said. Of the 343 total adverse events reported, only 8 (2.3%) were considered treatment related, she added.

“In infectious disease, it’s the beginning” for monoclonal antibody therapy, Dr. Gonzalez said. “But, it appears to be the future because … it is a more specific treatment, and there is no resistance.”

The study suggests adjunctive treatment with AR-301 appears safe for treatment of hospital-acquired bacterial pneumonia, she noted. The next step will be to confirm the findings in a larger, follow-up study that includes more efficacy outcomes, Dr. Gonzalez added.

Dr. Gonzalez reported having no relevant disclosures. The study’s principle investigator is a scientific advisor for Aridis Pharmaceuticals, which is developing AR-301.

IDP@frontlinemedcom.com

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