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GED-0507 is a novel potential antifibrotic treatment option for pulmonary fibrosis

Cellular & Molecular Immunology volume 17, pages 1272–1274 (2020)Cite this article

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Idiopathic pulmonary fibrosis (IPF) is the prototype of a large and heterogeneous group of chronic progressive pulmonary disorders. No treatment is able to halt or reverse pulmonary fibrosis, although pirfenidone (Pirf) and nintedanib (Nint) have been shown to slow lung function decline and disease progression but with significant side effects. We evaluated the safety and efficiency of GED-0507, an original selective peroxisome proliferator-activated receptor (PPAR)-γ modulator, in a murine model of bleomycin (BLM)-induced pulmonary fibrosis compared to those of Pirf and Nint. Preventive and curative administration of GED-0507 improved the loss of body weight and extension of lung fibrotic lesions. When given as a preventive treatment, GED-0507 also abrogated the mortality rate and histological fibrosis score, as well as the lung levels of hydroxyproline.

IPF is an aggressive disorder that is characterized by inexorable scarring of the lung parenchyma and loss of pulmonary function. With more than 100,000 individuals affected, 30,000–40,000 new cases are diagnosed each year in the United States alone, and with an average life expectancy of 3–5 years after diagnosis, IPF represents a substantial economic burden on global health care.1 Therapeutic approaches to IPF have evolved considerably over the last two decades, and in 2015, the ATS/ERS/JRS/ALAT guidelines made a conditional (i.e., weak) recommendation for the use of two drugs, pirfenidone (Pirf) and nintedanib (Nint).2 These two drugs are similarly efficacious in slowing the functional decline and disease progression in IPF; however, their safety and tolerability profile requires careful patient education and attention to potential side effects.3 In this study, we explored the safety and efficacy of the original PPARγ modulator GED-0507-34-Levo (GED-0507) in halting or even reversing pulmonary fibrosis in mice.

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Fig. 1: Study design and main findings following preventive and curative administration of GED-0507.

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Acknowledgements

We thank Nogra Pharma Ltd., Dublin, Ireland, for partly funding this study. Nogra Pharma Ltd. has filed a patent for the use of GED-0507 in inflammatory/fibrotic diseases.

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Authors and Affiliations

  1. The University of Lille, INSERM, U1286 – Infinite – Institute for Translational Research in Inflammation, Lille, France

    Silvia Speca, Philippe Chavatte & Pierre Desreumaux

  2. Intestinal Biotech Development, Lille, France

    Caroline Dubuquoy & Christel Rousseaux

  3. Laboratoire de Pharmacie Clinique, Faculté des Sciences Pharmaceutiques et Biologiques, Lille, France

    Philippe Chavatte

  4. CHU Lille, Hepato-Gastroenterology Department, Lille, France

    Pierre Desreumaux

  5. Respiratory Disease Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy

    Paolo Spagnolo

Authors
  1. Silvia Speca
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  2. Caroline Dubuquoy
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  4. Philippe Chavatte
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  6. Paolo Spagnolo
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Corresponding author

Correspondence to Paolo Spagnolo.

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Competing interests

P.D. reports personal fees from PPM Services, during the conduct of the study; personal fees from Ferring, Switzerland; personal fees from Intralytix, USA; personal fees from Lesaffre, France; personal fees from KitoZyme, Belgium; personal fees from Abbott, France; personal fees from Janssen, France; personal fees from MSD, France; personal fees from Norgine, France; personal fees from Pfizer, France; personal fees from Takeda, France, outside the submitted work. P.S. reports personal fees from PPM Services during the conduct of the study; grants, personal fees and non-financial support from Roche; grants and non-financial support from PPM Services; grants, personal fees and non-financial support from Boehringer-Ingelheim; personal fees from RedX Pharma; personal fees from Galapagos; personal fees from Chiesi, outside the submitted work. S.S., C.D., C.R., and P.C. have nothing to disclose.

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Speca, S., Dubuquoy, C., Rousseaux, C. et al. GED-0507 is a novel potential antifibrotic treatment option for pulmonary fibrosis. Cell Mol Immunol 17, 1272–1274 (2020). https://doi.org/10.1038/s41423-020-0394-y

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