Phase 2a Trial Will Test Molgradex in CF Patients with NTM Infections

Phase 2a Trial Will Test Molgradex in CF Patients with NTM Infections

Savara Pharmaceuticals has launched a Phase 2a clinical study to evaluate the effectiveness of Molgradex in cystic fibrosis (CF) patients with chronic nontuberculous mycobacterial (NTM) lung infections.

Molgradex is an inhaled form of artificially produced human protein granulocyte-macrophage colony-stimulating factor (GM-CSF), which normally is produced and secreted by several types of immune cells to trigger a response against pathogens (disease-causing organisms).

According to Savara, NTM is estimated to affect 50,000 to 80,000 individuals in the U.S. NTM infections often become chronic, and may require extended treatment with several antibiotics. Still, treatment failure rates are high. CF patients are particularly susceptible to NTM infection.

“People living with CF who have chronic NTM lung infection are in need of improved treatment options to complement current antibiotic regimens,” Rob Neville, CEO at Savara, said in a press release.

“By stimulating the lung’s immune system, we expect Molgradex to enhance the body’s natural ability to fight infection,” Neville said.

The open-label Phase 2a study, ENCORE (NCT03597347), will test the effectiveness of Molgradex in about 30 CF patients with chronic pulmonary NTM infection — caused either by Mycobacterium avium complex (MAC) or Mycobacterium abscessus. The study will include participants who either are taking an antimycobacterial regimen, are intolerant or non-responsive to NTM antibiotics, or failed to fulfill the criteria to start antibiotic treatment.

Approximately 30 participants (aged 18 or older) will be enrolled. They will receive 300 micrograms of nebulizing Molgradex once daily for 48 weeks, followed by a 24-week follow-up period.

The study’s primary goal is three negative NTM cultures collected consecutively (with a four-week interval between them) from the sputum (a mixture of saliva and mucus from the respiratory tract) of participants. Secondary goals include other microbiological indicators, as well as lung function measurements, and patient-reported outcomes.

“Somewhat analogous to oncology immunotherapies, we believe anti-infective immunotherapy has the potential to transform the way many refractory lung infections are treated,” Neville said.

Savara also is testing Molgradex in a Phase 2a trial for NTM treatment in non-CF patients (NCT03421743), and in a Phase 3 study (NCT02702180) in patients with autoimmune pulmonary alveolar proteinosis, a rare autoimmune lung disorder.

The company also is conducting a Phase 3 trial (NCT03181932AVAIL) testing another product called AeroVanc (inhaled vancomycin), to treat persistent methicillin-resistant Staphylococcus aureus (MRSA) lung infections in CF patients.