DOD-funded study explores metformin as potential therapy for IPF

A clinical study led by Fernando Martinez, M.D., vice chair for clinical and translational research and academic chief of the Division of Pulmonary, Allergy and Critical Care at UMass Chan Medical School and funded by the Department of Defense (DOD) is targeting idiopathic pulmonary fibrosis (IPF).

The DOD-funded consortium project repurposes metformin, a drug commonly used to control sugar levels in people with Type 2 diabetes, to treat patients with IPF.

“There have been several lines of evidence that led to this trial,” Martinez, who serves as principal investigator, told Managed Healthcare Executive. “Numerous groups have highlighted the biology of metformin and related medications as modifying preclinical models of fibrosis. There are numerous suggested mechanisms, but a senescence (premature lung aging) effect is thought to be most likely. These effects have appeared to be independent of diabetes.”

What’s more, he explained, several groups have examined existing databases (e.g. Optum, prior clinical trials in IPF, registries) and suggested that metformin therapy in people wiht diabetes with IPF may have a positive effect on mortality rates,

“Whenever I propose a federally funded trial, I try to ensure that taxpayer dollars are used to achieve more than one goal,” Martinez said. “In this case, there are numerous such additional opportunities: Repurposing a cheap and well-tolerated drug would be a major addition for patients suffering from IPF and their families. If we can decrease hospitalizations, it’s favorable to health systems as well.”

The multicenter trial will involve approximately 55 Pulmonary Fibrosis Foundation (PFF) Care Centers and Veterans Affairs (VA) Medical Centers nationwide. In addition, it will assess the clinical utility of a newly developed blood test designed to identify IPF patients at heightened risk for adverse outcomes. The overall program aims to screen 800 patients, with roughly 400 of the patients identified as being at increased risk.

“It’s safe to say that pulmonary fibrosis is of interest to the DOD because epidemiological data have demonstrated that veterans are at increased risk for disease,” Martinez said. “Moreover, the DOD has been forward thinking in introducing new ways to efficiently study future therapies across a broad range of patient groups by investing in novel pragmatic clinical trial infrastructure that will integrate VA Medical Centers with the PFF care network.”

What’s more, he noted incorporating VAHS with expertise in IPF into the PFF national registry would be a major benefit for the VA and its expanding goals.

“The study incorporates a composite clinical endpoint that extends the field beyond just lung function,” Martinez said. “The latter has been the regulatory paradigm for industry. The study expands the use of pragmatic study designs in the IPF space.”

The study also includes a newly developed blood test aimed at identifying patients at higher risk for adverse outcomes.

“This proteomic classifier provides a potential proof of principle for a proteomic predictor,” Martinez said. “This hopefully would introduce the potential of precision based therapy to patients most likely to benefit from this particular therapy. Whether this marker, which is purely research right now, will be used clinically in the future is a more complex questions that will need to be specifically addressed subsequently.”

If metformin proves effective in slowing or altering the course of IPF, it would be a major advance, particularly if it is improving clinical outcomes that are very relevant to patients and their caregivers.

“A positive study would also support the use of clinical composite endpoints and not just lung function,” Martinez said. “This would provide an expanded paradigm for FDA/EMA and industry as they develop new therapies in the era of combined antifibrotics.”