Inventiva announces that FDA lifts target class clinical hold which allows long-term clinical studies with lanifibranor in NASH
May 23, 2019
Daix (France), May 23, 2019 – Inventiva (Euronext: IVA), a clinical-stage biopharmaceutical company developing oral small molecule therapies for the treatment of diseases in the areas of fibrosis, lysosomal storage disorders and oncology, today announced that the U.S. Food and Drug Administration (FDA) has lifted for lanifibranor the clinical hold in place on the peroxisome proliferator-activated receptor (PPAR) target class. This decision enables Inventiva to conduct clinical trials equal to or longer than six months evaluating lanifibranor for the treatment of NASH. This authorization follows the review of the drug candidate’s two-year carcinogenicity studies by the FDA’s Executive Carcinogenicity Assessment Committee (ECAC).
The FDA decision, which confirms lanifibranor’s benign safety profile, represents a key milestone for Inventiva as it removes a key obstacle preventing the Company from initiating the long-term Phase III clinical trials necessary to obtain marketing approval for the drug candidate for the treatment of NASH.
Some single PPAR and dual PPAR agonists have been associated with toxicity and adverse effects on the heart, kidney, skeletal muscle and bladder, as well as on body weight, water retention and bone mineral density. As a result, FDA regulations regarding the PPAR class of compounds require two-year carcinogenicity and one-year in vivo toxicity studies to be performed prior to a product candidate entering clinical trials longer than six months. In accordance with these requirements, Inventiva launched three long-term toxicological studies of lanifibranor in 2015. Inventiva first evaluated lanifibranor in a 12-month primate toxicological study, in which the administration of the drug candidate was not associated, at any dose-level tested, with the toxicity and adverse effects linked to single and dual PPAR agonists. In parallel, lanifibranor was evaluated in two 2-year carcinogenicity studies in rats and mice designed to identify any potential carcinogenic risk. In these two studies, lanifibranor was not associated with any carcinogenic effect relevant to humans, up to the highest dose tested.
Pierre Broqua, Chief Scientific Officer and cofounder of Inventiva, said: “The FDA’s positive decision is consistent with the favorable and differentiating safety profile of our lead product candidate as already observed in pre-clinical and clinical trials to date confirming lanifibranor’s differentiation from other PPAR agonists. This decision is key as it removes a significant barrier to moving ahead with our planned Phase III pivotal trials in NASH.”
Lanifibranor, Inventiva’s lead product candidate, is an orally-available small molecule that acts to induce antifibrotic, anti-inflammatory and beneficial metabolic changes in the body by activating all three peroxisome proliferator-activated receptor (“PPAR”) isoforms, which are well-characterized nuclear receptor proteins that regulate gene expression. Lanifibranor is a PPAR agonist that is designed to target all three PPAR isoforms in a moderately potent manner, with a well-balanced activation of PPARα and PPARδ, and a partial activation of PPARγ. While there are other PPAR agonists that target only one or two PPAR isoforms for activation, lanifibranor is the only pan-PPAR agonist in clinical development. Inventiva believes that lanifibranor’s moderate and balanced pan-PPAR binding profile contributes to the favorable safety and tolerability profile that has been observed in clinical trials and pre-clinical studies to date.
Inventiva is currently evaluating lanifibranor in a Phase IIb clinical trial for the treatment of non-alcoholic steatohepatitis (“NASH”), a common and progressive chronic liver disease, for which there is currently no approved therapy.
Lanifibranor, its lead product, is an anti-fibrotic treatment acting on the three alpha, gamma and delta PPARs (peroxisome proliferator-activated receptors), which play key roles in controlling the fibrotic process. Its anti-fibrotic action targets two initial indications with substantial unmet medical need: NASH, a severe and increasingly prevalent liver disease already affecting over 30 million people in the United States, and systemic sclerosis, a disease with a very high mortality rate and for which there is no approved treatment to date.
Inventiva is also developing a second clinical program with odiparcil (IVA 336) for the treatment of patients with mucopolysaccaridosis type VI (or Maroteaux-Lamy syndrome), a rare and severe gene disease affecting children. Odiparcil has also the potential to address other MPS types, characterized by the accumulation of chondroitin or dermatan sulfate (MPS I or Hurler/Sheie syndrome, MPS II or Hunter syndrome, MPS IVa or Morquio syndrome and MPS VII or Sly syndrome). Inventiva is also developing a portfolio of early research projects in the field of oncology.
Inventiva benefits from partnerships with world-leading research entities such as the Institut Curie in the field of oncology. Two strategic partnerships have also been established with world-class major pharmaceutical companies AbbVie and Boehringer Ingelheim in the fields of autoimmune diseases (specifically in psoriasis) and fibrosis respectively. These partnerships provide milestone payments to Inventiva upon the achievement of pre-clinical, clinical, regulatory and commercial milestones, in addition to royalties on the products resulting from the partnerships.
Inventiva employs over 100 employees and owns R&D facilities near Dijon, acquired from the international pharmaceutical group Abbott. The Company owns, a proprietary chemical library of over 240,000 molecules as well as integrated biology, chemistry, ADME and pharmacology platforms.
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