Non-alcoholic Steato-hepatitis (NASH)
Non-alcoholic steato-hepatitis (NASH), a severe and chronic form of non-alcoholic fatty liver disease has become a leading contributor to the need for liver transplantation. NASH increases 5 to 10 fold the risk of liver related mortality and is expected to become the leading cause of liver transplantation by 2020.
There are no pharmaceutical treatments currently approved in NASH and treatment options are limited to lifestyle change, weight loss and to physical therapy such as bariatric surgery. The high level of unmet medical need, growing patient population (today in the US alone it is estimated that more than 30 million people have NASH, of which more than 14 million are at a fibrotic stage of the disease) and the commercial potential of the NASH market makes it an attractive opportunity for new drug development.
Systemic sclerosis (SSc) is a complex, multiorgan, rare disease, affecting the immune system, the microvascular system and the connective tissue. This disease involves mostly skin but also lung, heart, gastrointestinal tract and kidneys. Organ progressive failures make SSc a severe and lethal disease with a high death toll.
The clinical visibility of skin affection has led to its original name “scleroderma”, from the Greek words skleros (hard or indurated) and derma (skin) and the clinical recognition of two patterns of skin sclerosis provided the basis for the classification into two subtypes, called limited and diffuse cutaneous SSc. Both forms of SSc cause severe physical, psychosocial and life threatening consequences for patients.
So far only symptomatic drugs with limited therapeutics effects are available to temper or delay this devastating process. Lanifibranor by acting on several components of fibrosis and on several organs could offer a curative treatment for SSc patients, which can improve dramatically the current symptomatic treatment options.
Lanifibranor has received orphan status designation from EMA and FDA in this indication and the clinical development plan has been validated by the EMA.
Lanifibranor is a new chemical entity that activates the three PPAR (peroxisome proliferator-activated receptor) isoforms: α, δ and γ.The product has demonstrated good tolerability, safety and efficacy in phase I and phase IIa studies, in approximately 100 healthy volunteers and 60 type 2 diabetic patients.
Lanifibranor's anti-fibrotic efficacy was demonstrated in several in vitro and in vivo preclinical studies, where Lanifibranor induced the regression of pre-existing fibrotic damage in the liver and in the skin and prevented further fibrosis from developing. Lanifibranor also demonstrated anti-fibrotic activities in relevant models of lung and kidney fibrosis. Based on these results Inventiva has decided to target liver and skin fibrosis where Lanifibranor results have been promising and to select two indications for their high unmet medical need: NASH and SSc.
Lanifibranor also benefits from a strong market exclusivity thanks to IP on composition of matter granted in most of the countries of the world, including Europe, USA, Japan and China.
Two phase IIb trials (NATIVE: Nash trial to validate Lanifibranor efficacy and FASST: For a systemic sclerosis treatment) are currently ongoing and recruiting patients.