Inventiva announces further progress achieved in the clinical development of lanifibranor for the treatment of NASH
21 February 2019
Daix (France) February 21st, 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 the screening of the first patient in the United States for its Phase IIb NATIVE (NASH Trial to Validate IVA337 Efficacy) clinical trial evaluating lanifibranor, the Company’s lead product candidate, for the treatment of non-alcoholic steatohepatitis (NASH), a common and progressive chronic liver disease for which there is currently no approved therapy. Inventiva also announced that the NATIVE Data Safety Monitoring Board (DSMB) held its second meeting and recommended that the trial continue as planned.
The screening of the first patient in the United States follows the positive review by the U.S. Food and Drug Administration (FDA) of the NATIVE trial protocol and the inclusion of 14 sites in the United States in the trial, which brought the total number of sites involved to 91. Out of 225 patients expected to be enrolled in the trial, 155 patients have been randomized, and 71 patients have already completed the six-months treatment. The NATIVE trial continues to progress as planned and results are anticipated in the first half of 2020.
Pr Sven Francque, M.D., Ph.D. from the Antwerp University Hospital and Co-Principal Investigator, said: “The news of the first patient screened in the U.S. and the opening of 14 sites represents great progress. We expect to open 5 additional sites in Europe to further accelerate patient recruitment. Given the study design and lanifibranor’s mechanism of action, we believe that the results of the NATIVE trial, if positive, will support lanifibranor’s move into the pivotal Phase III trial.”
Pr Manal Abdelmalek, M.D., M.P.H. from Duke University, who agreed to act as Co-Principal Investigator with Pr Sven Francque, stated: “I am very pleased to be a part of this important trial and am excited by the profile of lanifibranor, a drug that is designed to act on many features of NASH by combining anti-fibrotic and anti-inflammatory activities with metabolic benefits, including improvement of insulin sensitivity.”
“The NATIVE trial is rolling out in the United States as planned and we are excited to add U.S. sites to the study, making NATIVE a truly international trial. We are thrilled to welcome Pr Abdelmalek, a renowned hepatologist, to the Steering Committee of the NATIVE trial and we look forward to finalizing recruitment over the coming months,” added Inventiva’s Chief Medical Officer, Marie-Paule Richard, M.D.
In addition, the NATIVE DSMB has reviewed the available safety data from the trial and recommended, for the second time, that the trial continue without modification to the protocol. The positive outcome of this second DSMB review is consistent with the results of long-term toxicological studies, as well as of Phase I and Phase II clinical trials, which have shown that lanifibranor is associated with a favorable safety profile.
Lanifibranor, Inventiva’s lead product candidate, is an orally-available small molecule that acts to induce anti-fibrotic, 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, 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.
About the NATIVE Phase IIb trial
The NATIVE (NAsh Trial to Validate IVA337 Efficacy) clinical trial is a 24-week treatment, randomized, double-blind, placebo-controlled Phase IIb clinical trial evaluating lanifibranor in the treatment of patients with non-alcoholic steatohepatitis (“NASH”). The goal of the trial is to assess the effect of lanifibranor on the improvement in liver inflammation and ballooning, which are two of the markers of the resolution of NASH. To be considered for inclusion, patients must have: a diagnosis of NASH confirmed by liver biopsy; a cumulative score of inflammation and ballooning (as measured using the steatosis, activity and fibrosis, or “SAF”, scoring system) of three or four out of four, indicating the presence of moderate to severe inflammation and ballooning; a steatosis score greater than or equal to one, indicating the presence of moderate to severe steatosis; and a fibrosis score less than four, indicating the absence of cirrhosis. The primary endpoint of the trial is a reduction in the combined inflammation and ballooning score of two points compared to baseline, without worsening fibrosis. Secondary endpoints include NASH resolution, improvements in each of the steatosis, inflammation, ballooning and fibrosis scores from baseline as measured using the SAF score, improvements in various other fibrosis measures, improvements in several metabolic markers, improvements in steatosis, inflammation and ballooning as measured using the “NAS” score, and safety.
The trial is expected to enrol 225 patients with NASH at more than 90 sites in Europe, the United States, Canada, Australia and Mauritius. Results of the trial are expected in the first half of 2020.
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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