Phase 2A of Rare Lung Infection Treatment Initiated

A Phase 2a clinical study evaluating Molgradex was recently initiated by Savara, Inc.

The inhaled formulation of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) is intended for the treatment of nontuberculous mycobacterial (NTM) lung infection, and the OPTIMA study intends to evaluate the reduction of sputum samples without growth of non-tuberculosis mycobacteria during the treatment period, or sputum culture conversion. The drug is delivered via an investigational eFlow Nebulizer System.

The OPTIMA trial will enroll subjects with chronic M. abscessus or Mycobacterium avium complex (MAC) infection, with all subject having either antibiotic refractory infection or intolerance to standard NTM antibiotics.

“Treatment of NTM lung infection with long multi-drug antibiotic regimens is challenging, places significant burden on patients, and yet frequently fails to eradicate the infection,” stated Rachel Thomson, M.B.B.S., Ph.D., Thoracic Physician, Associate Professor, The University of Queensland, Australia and one of the coordinating investigators on the OPTIMA study in a press release. “Based on the emerging scientific rationale and the encouraging outcomes of the first clinical cases treated with inhaled GM-CSF, I believe Molgradex represents a promising novel approach into this disease desperate for more effective treatment options.”

Over a 24-week period two subgroups of subjects will be recruited: Group 1 will consist of subjects who remain sputum culture positive while currently receiving multidrug NTM guideline based on anti-mycobacterial regimen, which has been ongoing for at least 6 months prior to the baseline visit. Group 2 will consist of subjects who remain sputum culture positive, but have either never initiated treatment, or have stopped a multidrug NTM guideline based anti-mycobacterial regimen at least 28 days prior to screening as the result of lack of response or intolerance.

Participants will also be evaluated during a 12-week follow-up period.

“We believe that Molgradex may significantly improve patient outcomes by stimulating the innate immune system in the lungs, as compared with targeting bacteria directly, thereby avoiding problems of antibiotic resistance and antibiotic intolerance,” said stated Rob Neville, chief executive officer of Savara.

Sputum culture conversion will serve as the primary endpoint of the trial, and is defined as at minimum 3 consecutive sputum samples without growth of NTM. Secondary endpoints include: the number of subjects with sputum smear conversion to negative, defined as at least three consecutive negative acid-fast bacilli (AFB) stained sputum smears on microscopy among subjects who were smear positive at baseline; the number of subjects with durable sputum culture conversion, defined as sputum culture conversation at or before week 24 and culture still negative growth of NTM at 12-week follow-up; the number of subjects with durable sputum smear conversion, defined as sputum smear conversion at or before week 24 and AFB stained smear still negative for NTM at 12-week follow up among subjects who were smear positive at baseline; and other microbiological indicators, exercise capacities and patient-reported outcomes.

“We believe Molgradex will be eligible for Orphan Status as well as Qualified Infectious Disease Product Status, and if the results of the OPTIMA study meet our expectations, the product may also qualify for Breakthrough Therapy Designation,” said Neville.

The drug is also currently in Phase 3 development for autoimmune pulmonary alveolar proteinosis (PAP), an indication for which it has already been granted orphan drug designation for the treatment of PAP by both the U.S. Food and Drug Administration (FDA) and European Union (EU).

For more from the rare disease community, follow Rare Disease Report on Facebook and Twitter.