2 CF Case Reports Show Successful Use of GM-CSF for Treating Nontuberculous Mycobacteria

Savara Pharmaceuticals announced the publication of two case reports demonstrating that inhaled granulocyte-macrophage colony stimulating factor (GM-CSF) either eradicated or dramatically reduced Mycobacterium abscessus (M. abscessus) infection, improved clinical outcomes, and was well-tolerated in patients with cystic fibrosis (CF).

The results were published in the European Respiratory Journal in an article titled “Inhaled Granulocyte-Macrophage Colony Stimulating Factor for Mycobacterium Abscessus in Cystic Fibrosis.”

The case report explored the use of aerosolized GM-CSF for the treatment of M. abscessus, which is a species of multidrug-resistant nontuberculous mycobacteria (NTM) that is sometimes present in CF patients.

NTM lung infection poses a significant therapeutic challenge as these bacteria allow them to evade the normal killing action of alveolar macrophages, an immune cell that is responsible for killing bacteria in the lungs.

“NTM, and in particular M. abscessus, are very difficult to eradicate in patients with chronic lung disease, such as CF, and seriously affect patient morbidity,” Mark E. Wylam, MD, the study’s senior author and a pulmonologist and critical care specialist at the Mayo Clinic in Rochester, Minnesota, said in a press release.

Previous studies in animal models, such as mice that lack GM-CSF, have demonstrated that GM-CSF plays an important role in activating these macrophages to kill mycobacteria.

The benefit of GM-CSF is that it is not an antibiotic, as many bacterial species are becoming resistant to antibiotics. In particular, M. abscessus is the one of the organisms most resistant to antibiotics.

The method of action of GM-CSF is that it stimulates the human immune system without targeting the bacteria directly, which bypasses the problem of antibiotic resistance.

GM-CSF has been been successfully used to treat pulmonary alveolar proteinosis (PAP), a rare lung disease where the major complication is infection with unusual bacteria. This has led researchers at the Mayo Clinic to treat NTM infection with GM-CSF.

“Both of our patients had a long history of M. abscessus infection that we had not been successful in treating, and both were experiencing a decline in their clinical condition, but when started on inhaled GM-CSF treatment, both demonstrated rapid microbiological response and clinical improvement,” Wylam said.

Molgradex is an inhaled GM-CSF developed by Savara, and is currently in Phase 3 development for PAP and in preparation for Phase 2a development for NTM lung infection.

“We believe the Mayo Clinic case reports strongly reinforce the scientific rationale for treatment of NTM lung infection using Molgradex, our proprietary inhaled form of GM-CSF, and we are excited to be initiating our Phase 2a study of Molgradex in NTM infection later this quarter,” said Rob Neville, CEO of Savara.

Savara plans to start a 30-patient, multi-center, open-label Phase 2a clinical trial to determine the efficacy and safety of Molgradex for the treatment of chronic NTM lung infection.

“Whereas Molgradex may be effective on its own against NTM infection, we envision it may also be useful in combination with any of the current or future antibiotic regimens,” Neville said.

“Furthermore, if Molgradex proves to be effective against NTM infection, such effectiveness could open up a whole new avenue to study Molgradex for the treatment of other chronic lung infections associated with deficiency of the innate immune system,” he added.