There was no significant difference between placebo and lanifibranor, Inventiva Pharmaceuticals’ investigational treatment for systemic sclerosis, in alleviating skin fibrosis in a Phase 2b study, the company announced.
Based on the results, Inventiva will no longer proceed with the clinical development of lanifibranor for scleroderma. It will continue evaluating lanifibranor for the treatment of non-alcoholic steatohepatitis (NASH), a chronic liver disease.
Lanifibranor is a peroxisome proliferator-activated receptor (PPAR) agonist. PPAR receptor proteins play an essential role in regulating the anti-fibrotic and anti-inflammatory response of the body. As an agonist, lanifibranor binds and increases PPAR activity.
The Phase 2B FASST trial (NCT02503644) compared the efficacy and safety of two different doses of lanifibranor (400 and 600 mg, twice daily) to placebo in patients with diffuse cutaneous systemic sclerosis (dcSS) — estimated to affect about 35% patients with systemic sclerosis.
There were 145 dcSS patients (ages 18-75) in the FASST study. They were randomly assigned to receive either 400 mg lanifibranor twice daily, 600 mg lanifibranor twice daily, or placebo.
Patients received the treatment for 48 weeks, in addition to their standard-of-care treatment (which in most cases included immunosuppressive therapies).
Skin thickness — assessed through the modified Rodnan Skin Score (mRSS) — is an indicator of skin fibrosis, and was used to evaluate the efficacy of the treatment. The mRSS measures skin thickness at 17 points on the body, on a scale of zero to three. The lower the mRSS score, the thinner the skin. mRSS was assessed before the start of the treatment (baseline), and after 48 weeks.
Researchers found that both doses of lanifibranor and the placebo treatment lowered the average mRSS score, but there was no significant difference among the three groups. The mean mRSS score at 48 weeks in the lanifibranor 400 mg, lanifibranor 600 mg, and placebo groups were lowered by 3.7, 4.3, and 4.9 from baseline, respectively.
Similarly, there was no difference between placebo and lanifibranor treatments in slowing the overall progression of the condition, or in improving lung function.
“It appears that the presence of background [immunosuppressive] therapy produced a strong placebo effect and limited the number of patients progressing in dcSS,” Yannick Allanore, co-principal investigator of the FASST trial, and professor of rheumatology at the Hôpital Cochin in Paris, said in a press release.
Although lanifibranor did not significantly alleviate skin fibrosis, the patients reported the treatment to be beneficial as per their responses to the global assessment of disease activity questionnaire.
Also, lanifibranor was found to be safe. Among the adverse events reported, only one patient treated with the high dose of lanifibranor had peripheral edema. No adverse kidney or heart events were reported.
“We regret the study results, but we are satisfied both by lanifibranor patients’ well-being, expressed in their global assessment, and lanifibranor’s favorable safety profile observed in the trial, including in combination with immunosuppressive drugs,” said Christopher Denton, co-principal investigator of the trial, and professor at the University College of London, U.K.
“We are disappointed by the results of the FASST clinical trial in dcSS,” said Frédéric Cren, chairman and CEO of Inventiva. “While we have decided to discontinue the lanifibranor program in SSc, we are very grateful for the dedication and commitment of patients, caregivers, investigators and our team to this program.
“We remain confident in lanifibranor’s unique mechanism of action and will therefore continue to move forward, as planned, with its clinical development in the treatment of NASH.”