Potential IPF Treatment Limits Weight Loss, Lung Scarring in Mouse Model

Potential IPF Treatment Limits Weight Loss, Lung Scarring in Mouse Model
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Nogra Pharma’s experimental therapy GED-0507 limited body weight loss and the extension of lung scarring (fibrosis) — to a similar or greater extent than two approved anti-fibrotic therapies used as comparators — in mice with induced pulmonary fibrosis (PF), a study reported.

These findings suggest that GED-0507 may be a therapeutic option for PF, and it could advance into clinical trials in people with idiopathic pulmonary fibrosis (IPF), the researchers noted.

The study, “GED-0507 is a novel potential antifibrotic treatment option for pulmonary fibrosis,” was published as a correspondence in the journal Cellular & Molecular Immunology.

GED-0507, also known as GED-0507-34-Levo, is a small molecule that works by selectively activating the peroxisome proliferator-activated receptor (PPAR) gamma (PPAR-gamma), a protein that controls inflammatory and fibrotic processes. Particularly, PPAR-gamma is known to act against TGF-beta 1, the most well-known pro-fibrotic protein.

GED-0507’s specific structure is thought to provide powerful anti-inflammatory and anti-fibrotic properties with a better safety profile than other PPAR and PPAR-gamma activators, which can carry several significant side effects.

Preclinical studies found no side effects in animals treated with GED-0507, even at very high and repeated doses, and the therapy was well-tolerated in people with inflammatory bowel disease within Phase 1 and 2 clinical trials, the researchers reported.

The therapy was designated an orphan drug by the European Commission as a potential IPF treatment in 2018.

Researchers evaluated the safety and effectiveness of GED-0507 against two approved IPF therapies — Ofev (nintedanib, marketed by Boehringer Ingelheim) and Esbriet (pirfenidone, marketed by Genentech, a Roche company) — in a mouse model of PF.

The team used the bleomycin-induced lung fibrosis mouse model, in which mice are exposed to bleomycin — a highly toxic chemotherapy agent — to induce lung fibrosis.

To evaluate the effects of preventive treatment, mice initiated daily treatment with GED-0507 or Esbriet a day after bleomycin administration. To reflect its potential as a curative treatment, mice were given either GED-0507, Esbriet, or Ofev once a day, starting 14 days after bleomycin administration.

Results at 28 days after PF induction showed that preventive treatment with GED-0507 arrested weight loss, significantly reduced lung fibrosis, lesion extension, and the levels of hydroxyproline in the lungs (a marker of collagen deposition, associated with fibrosis), and prolonged the life of mice with induced IPF.

Notably, these effects were clearly superior to those of Esbriet, which particularly showed no benefit in body weight or survival.

As a curative treatment, GED-0507 led to similar benefits as Ofev in preventing weight loss and lessening the extension of fibrotic lesions in mice with established PF, while Esbriet showed no benefit. Neither treatment significantly improved the survival or lowered the amount of lung fibrosis and hydroxyproline levels in these mice.

Based on the results, the research team concluded that “preventive and curative administration of GED-0507 [reduced] the loss of body weight and extension of lung fibrotic lesions,” the researchers wrote, adding that the therapy “displays beneficial effects on lung fibrosis, and may represent a promising therapeutic option for pulmonary fibrosis in humans.”

The team also noted that GED-0507 “is ready to be tested in a Phase 1b clinical trial in patients with IPF.”

The study was partly funded by Nogra Pharma, which has filed a patent for the use of GED-0507 in inflammatory/fibrotic diseases.

Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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