2 CF Patients with Lung Infections Due to M. abscessus Show Signs of Cure Using GM-CSF, Savara Reports

Two cystic fibrosis (CF) patients being treated for lung infections related to Mycobacterium abscessus — a multidrug-resistant nontuberculous mycobacteria (NTM) — using inhaled granulocyte-macrophage colony stimulating factor (GM-CSF) now both show signs of cure, Savara Pharmaceuticals announced.

M. abscessus accounts for about 35 percent of NTM infections in cystic fibrosis patients in North America, researchers report.

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

In the first CF patient, aerosolized GM-CSF treatment eradicated M. abscessus infection, and in the second initially led to a strong decline in bacterial burden.

Newly released data show that continued GM-CSF treatment appear to have eradicated M. abscessus infection in the second patient as well, and without the use of antibiotics targeting NTM.

This patient reached what microbiologists call culture conversion — when two consecutive sputum samples, taken at least 30 days apart, are negative for the presence of the bacteria. Culture conversion is a key clinical milestone meaning that a patient is responding to treatment.

GM-CSF is not an antibiotic and so these results are promising, especially since many bacterial species, in particular M. abscessus, are becoming resistant to standard antibiotics.

“This is a remarkable result given that this second subject, unlike the first one, was not treated with NTM antibiotics,” Mark E. Wylam, MD, the study’s senior author, said in a press release.

“Both subjects remain on aerosolized GM-CSF and have experienced clinically meaningful improvements in weight gain and lung function. I believe these case studies strongly reinforce the scientific rationale for the treatment of NTM lung infection using inhaled GM-CSF, and I look forward to the results of Savara’s ongoing OPTIMA study,” Wylam added.

A Phase 2a clinical trial, OPTIMA (NCT03421743) is a multi-center, open-label study currently recruiting participants to investigate the efficacy and safety of Molgradex – Savara’s inhaled GM-CSF – as a therapy for chronic NTM lung infection.

The trial aims to recruit 30 people infected with either M. abscessus or Mycobacterium avium complex (MAC), two forms of NTM, at sites in Australia and the U.K. Eligible patients must be intolerant to standard NTM antibiotics or have an antibiotic-resistant infection.

Patents will be treated for 24 weeks with Molgradex, followed by a 12-week observational period.

The study’s primary goal (endpoint) is to evaluate sputum culture conversion, defined as at least three consecutive negative sputum cultures. Secondary endpoints include other microbiological indicators, exercise capacity, and patient-reported outcomes.

Depending on patient recruitment, researchers expect to release top-line trial results in the first half of 2019.