France-based Inventiva reports positive trial results for its FASST (For a Systemic Sclerosis Treatment) clinical trial evaluating its lanifbranor investigational drug for treatment of patients with diffuse cutaneous systemic sclerosis (dcSSc), a rare, progressive autoimmune, rheumatic disease with frequent serious adverse events and high unmet medical need.
What is Diffuse Cutaneous Systemic Sclerosis (DCSSC)?
It is an autoimmune disease of the connective tissue. It is characterized by thickening of the skin caused by accumulation of collagen, and by injuries to small arteries. There are two forms of scleroderma: localized and systemic. The localized form affects the skin of only the face, hands and feet. The systemic forms (limited or diffuse cutaneous) involve those and in addition, may progress to visceral organs (heart, kidney, lungs, etc.). Prognosis is determined by the form of the disease and the extent of visceral involvement. Patients with limited cutaneous scleroderma have a 10-year survival rate of 75%; less than 10% develop pulmonary arterial hypertension after 10 to 20 years. Patients with diffuse cutaneous scleroderma have a 10-year survival rate of 55%. Death is most often caused by lung, heart and kidney involvement. Reports include risk of cancer as well.
It is a rare disease with annual incidence of 50 to 300 per million people. The number in the U.S. afflicted by the disease could be in the millions.
What is the FASST Trial?
The FASST clinical trial is a one-year, double-blind, randomized, A placebo-controlled Phase IIb clinical trial evaluating lanifibranor in the treatment of patients with diffuse cutaneous systemic sclerosis (“dcSSc”), which affects approximately 35% of patients with systemic sclerosis (“SSc”). The primary endpoint of the trial was a mean absolute change from baseline to week 48 in the modified Rodnan Skin Score (“mRSS”), which assesses skin thickness across 17 defined points on the body on a scale of zero, indicating normal skin, to three, indicating severe thickness. The mRSS is a clinically validated and FDA-accepted endpoint measuring the evolution of skin fibrosis, which is known to be correlated with internal organ fibrosis. In addition, secondary endpoints for the trial included changes in forced vital capacity (“FVC”), which is an FDA-accepted endpoint measuring pulmonary function, overall progression of the disease (assessed as the absence of rescue therapy and of severe organ involvement, such as kidney failure), changes in gastrointestinal health, and safety.
What were FASST TRIAL Results
The FASST clinical trial did not meet its primary endpoint of a mean absolute change from baseline to week 48, relative to placebo, in the modified Rodnan Skin Score (“mRSS”), which assesses skin thickness across 17 defined points on the body on a scale of zero, indicating normal skin, to three, indicating severe thickness. There was a decrease in the average mRSS observed in active and placebo arms with only four patients reporting to have increases in mRSS scores over the course of the trial.
|800mg lanifibranor||1200mg lanifibranor||Placebo|
|Number of patients||49||48||48|
|Mean baseline mRSS (SD)||18.2 (3.8)||17.8 (3.9)||17.1 (-3.7)|
|Mean absolute change of mRSS from baseline to week 48 (SD3)||-3.7 (4.2)||-4.3 (5.0)||-4.9 (4.6)|
While the trial did not meet any of the secondary endpoints, lanifibranor showed a favorable trend in patients’ global assessment of disease activity with a mean absolute change in visual analog scale (p=0.08) from baseline versus placebo indicating a perceived benefit by patients.
Within this fragile and poly-medicated population, lanifibranor was observed to be associated with a favorable safety profile, with no adverse interactions with immunosuppressive background therapies observed. The proportion of patients with at least one adverse event was similar across the three patient groups.
Who is the Commercial Sponsor?
Based in France, Inventiva S.A., a biopharmaceutical company, develops drugs for the treatment of fibrotic, cancer, and orphan diseases. Its lead product candidate is Lanifibranor that is in Phase IIb clinical trial to treat nonalcoholic steatohepatitis and systemic sclerosis. The company also develops Odiparcil, which is in Phase IIa clinical trial primarily for the treatment of mucopolysaccharidosis type VI disease; YAP-TEAD that is in preclinical stage to treat malignant mesothelioma and lung cancer; NSD2 for the treatment of multiple myeloma; and EPICURE for immuno-oncology treatment. It has partnership collaborations with the Institute Curie in the field of oncology; AbbVie for developing ROR? project that is used for the treatment of autoimmune diseases, as well as other projects relating to fibrosis; and Boehringer Ingelheim International GmbH for developing new treatments for idiopathic pulmonary fibrosis. Inventiva S.A. was founded in 2011 and is based in Daix, France.
What is Ianifibranor?
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 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.