All Mice with CF That Received Iclaprim for Pneumonia Survived, Study Shows

Patrícia Silva, PhD avatar

by Patrícia Silva, PhD |

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Pneumonia therapy iclaprim

All mice with cystic fibrosis that received iclaprim for a pneumonia infection survived, according to a study.

Motif Bio reported the finding, which involved the Staphylococcus aureus bacteria, and the results of another preclinical-trial study at the IDWeek 2017 conference in San Diego, Oct. 4-8.

Iclaprim is designed to kill bacteria that develop resistance to other antibiotics. Iclaprim has shown punch against a number of gram-positive versions of Staphylococci, including methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA). The difference between the two main structural-component class of bacteria are that gram-negative bacteria have thicker cell walls and are more difficult to treat than gram-positive bacteria.

One of the presentations that Motif Bio made at the conference was a poster session titled “Efficacy Evaluation of Iclaprim in a Neutropenic Rat Lung Infection Model with Methicillin-Resistant Staphylococcus aureus Entrapped in Alginate Microspheres.” Dr. David Huang, the company’s chief medical officer, presented its findings.

The study covered iclaprim’s ability to treat MRSA lung infections in mice with CF. Researchers compared iclaprim with another antibiotic, Shire’s Vancocin (vancomycin), and a placebo.

All 33 of the mice that received iclaprim survived, regardless of dose. Twenty-two of 24 — or 29 percent — of the mice treated with Vancocin survived. Only 14 out of the 29 mice in the place group, or 48 percent, survived.

Iclaprim also led to a significantly greater reduction in bacterial colony forming units (CFUs) in comparison with vancomycin. CFUs are an estimate of the number of bacteria cells in a sample.

Staphylococcus aureus is a common cause of pneumonia in patients with cystic fibrosis, and we do not believe that any antibiotic has been approved for this indication,” Huang said in a press release. “Some 80% or more of patients with cystic fibrosis die as a result of respiratory infections caused by a variety of bacteria, and MRSA infections have been growing in recent years. The encouraging new data presented today support developing iclaprim as a potential treatment option for MRSA infections in patients with cystic fibrosis.”

Another poster presentation at the conference dealt with iclaprim as a combination therapy. Dr. Amy Bryant of the Veterans Administration Medical Center in Boise, Idaho, made the presentation, titled “Effects of Iclaprim and Trimethoprim on Exotoxin Production by Methicillin-Resistant Staphylococcus aureus.

The study looked at the effectiveness of a combination of iclaprim and trimethoprim versus a combination of nafcillin and vancomycin in MRSA. The yardstick researchers used was each combo’s ability to reduce the amount of the toxin that bacteria generated.

Motif Bio researchers said the iclaprim-trimethoprim combo suppressed exotoxin production.

“Toxin suppression is an important therapeutic goal for severe infections due to toxin-producing gram-positive pathogens such as MRSA,” Huang said. “The in vitro [mice] data presented show that Iclaprim, at concentrations below those that inhibit bacterial growth, suppress toxin production. Iclaprim is fifteen-fold more active than trimethoprim, supporting the use of iclaprim to treat serious MRSA infections in hospitalized patients.”

In September of this year, the U.S. Food and Drug Administration granted iclaprim orphan drug status as a treatment for S. aureus lung infections in CF patients. The designation could help get iclaprim to market faster.

Motif Bio acquired iclaprim when the company merged with Nuprim in 2015. That same year, the FDA gave iclaprim fast track status and a qualified infectious disease product for bacterial skin and skin-structure infections.