PPARs are shown to be attractive therapeutic targets for the treatment of NASH, producing beneficial effects on the liver, improving features of the metabolic syndrome and mitigating the risk of related extra-hepatic diseases
Daix (France), November 2, 2020 – Inventiva (Euronext Paris and Nasdaq: IVA), a clinical-stage biopharmaceutical company focused on the development of oral small molecule therapies for the treatment of non-alcoholic steatohepatitis (NASH), mucopolysaccharidoses (MPS) and other diseases with significant unmet medical need, today announced the publication of a scientific paper on the role of peroxisome proliferator-activated receptors (PPARs) in the treatment of NASH by the peer-reviewed medical journal Nature Review Gastroenterology & Hepatology.
Published in coordination with the panNASH™ initiative, the article, entitled “Non-alcoholic steatohepatitis: the role of peroxisome proliferator-activated receptors”, discusses the current literature on Non-Alcoholic Fatty Liver Disease (NAFLD), describes the role of PPARs in NASH and related metabolic diseases, and summarizes the preclinical and clinical data on the use of PPAR agonists.
NAFLD is a multisystem disease with extra-hepatic disease implications, including the development of type two diabetes (T2DM) and cardiovascular diseases (CVDs). As the paper highlights, patients with NAFLD tend to present many features of the metabolic syndrome, such as central obesity, atherogenic dyslipidemia, hypertension, abnormal glucose tolerance and insulin resistance, and, in progression of NAFLD towards NASH, develop hepatic inflammation and often fibrosis.
According to the article, PPARs are key regulators of many of the adversely affected mechanistic pathways involved, making them attractive therapeutic targets for the treatment of NASH. Reportedly, PPARs produce beneficial effects on the liver, improve various features of the metabolic syndrome and mitigate the risk of developing related extra-hepatic diseases such as T2DM and CVDs.
The paper also discusses the well-known side effects of PPARs, explaining that those, including excessive body weight gain and fluid retention, can be controlled by the use of biomarkers and recover after stopping the treatment.
Jean-Louis Junien, Chairman of Inventiva’s Scientific Advisory Board, commented: “This scientific paper clearly illustrates that, although previous studies have shown limited efficacy of individual PPARs, ongoing clinical trials suggest a broader and more efficacious therapeutic potential especially of pan-PPAR agonists to treat the multisystem disease of NASH. This can in particular be attributed to their capacity to target different interrelated mechanisms in the pathophysiology of NASH. As such, lanifibranor, Inventiva’s lead drug candidate and only pan-PPAR agonist currently in development for the treatment of NASH, is ideally positioned in this field as evidenced by the recent topline results of the Company’s Phase IIb NATIVE clinical trial.”
Title of scientific paper:
“Non-alcoholic steatohepatitis: the role of peroxisome proliferator-activated receptors”
Date of publication:
October 22, 2020
Sven Francque1, Gyongyi Szabo2, Manal F. Abdelmalek3, Christopher D. Byrne4, Kenneth Cusi5, Jean-François Dufour6, Michael Roden7, Frank Sacks8 and Frank Tacke9
Link to the article:
The panNASH™ initiative is a working group consisting of a committee of international independent experts that aims to increase the visibility and contribute to a better understanding of NASH, to share their expertise and to establish best practices for the treatment of the disease.
Established in 2018, the initiative is supported by Inventiva and includes European and American medical experts in areas related to NASH such as hepatology, diabetes and cardiology, along with renowned scientific experts dedicated to promoting a better understanding of the physiopathological mechanisms involved in the disease. Their aim is to play an active role in developing and disseminating their NASH expertise among the scientific community, patients and other key stakeholders within the healthcare system.
In particular, the experts group helps to develop and share new findings about NASH through publications, conferences and training sessions, focusing on the development of the disease, the identification of patients at risk, clinical markers and associated health risks, as well as the development of new treatments. Specifically, the committee contributes to increasing the knowledge of pathological mechanisms ranging from metabolic disorders to fibrosis and comorbidities, with a focus on the modulating role played by PPARs (a,d,g subtypes).
Inventiva is a clinical-stage biopharmaceutical company focused on the development of oral small molecule therapies for the treatment of NASH, MPS and other diseases with significant unmet medical need.
Leveraging its expertise and experience in the domain of compounds targeting nuclear receptors, transcription factors and epigenetic modulation, Inventiva is currently advancing two clinical candidates, as well as a deep pipeline of earlier stage programs.
Lanifibranor, its lead product candidate, is being developed for the treatment of patients with NASH, a common and progressive chronic liver disease for which there are currently no approved therapies. Inventiva recently announced positive topline data from its Phase IIb clinical trial evaluating lanifibranor for the treatment of patients with NASH.
Inventiva is also developing odiparcil, a second clinical-stage asset, for the treatment of patients with subtypes of MPS, a group of rare genetic disorders. At the end of 2019, Inventiva published positive results from its Phase IIa clinical trial evaluating odiparcil for the treatment of MPS VI adult patients.
In parallel, Inventiva is in the process of selecting an oncology development candidate for its Hippo signalling pathway program. Furthermore, the Company has established a strategic collaboration with AbbVie in the area of autoimmune diseases. AbbVie has started the clinical development of ABBV‑157, a drug candidate for the treatment of moderate to severe psoriasis resulting from its collaboration with Inventiva. This collaboration enables Inventiva to receive milestone payments upon the achievement of pre-clinical, clinical, regulatory and commercial milestones, in addition to royalties on any approved products resulting from the collaboration.
The Company has a scientific team of approximately 70 people with deep expertise in the fields of biology, medicinal and computational chemistry, pharmacokinetics and pharmacology, as well as in clinical development. It also owns an extensive library of approximately 240,000 pharmacologically relevant molecules, approximately 60% of which are proprietary, as well as a wholly‑owned research and development facility.
Inventiva is a public company listed on compartment C of the regulated market of Euronext Paris (Euronext: IVA – ISIN: FR0013233012) and on the Nasdaq Global Market in the United States (ticker: IVA). www.inventivapharma.com
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1 Sven Francque: Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium.
2 Gyongyi Szabo: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
3 Manal F. Abdelmalek: Division of Gastroenterology and Hepatology, Department of Medicine, Duke University Health System, Durham, NC, USA.
4 Christopher D. Byrne: Nutrition & Metabolism, Human Development & Health, Faculty of Medicine, University Hospital Southampton, Southampton, UK.
5 Kenneth Cusi: Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA.
6 Jean-François Dufour: Hepatology, Department of Clinical Research, University Hospital of Bern, Bern, Switzerland & University Clinic for Visceral Surgery and Medicine, Inselspital, Bern, Switzerland.
7 Michael Roden: Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, University Clinics Düsseldorf, Düsseldorf, Germany & Institute for Clinical Diabetology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
8 Frank Sacks: Departments of Nutrition and Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA, USA & Channing Division, Department of Medicine Harvard Medical School and Brigham and Women’s Hospital, Boston, MA, USA.
9 Frank Tacke: Department of Hepatology & Gastroenterology, Charité University Medical Center, Berlin, Germany.