Inventiva’s drug candidate IVA337, currently in Phase 2 studies for both non-alcoholic steatohepatitis (NASH) and systemic sclerosis (SSc), has shown a good safety profile in monkeys, according to a 12-month non-human primate toxicology study conducted to meet the requirements of both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA).
In the study, 48 monkeys were assigned to one of three IVA337 dose regimens (100, 250 or 625 mg/kg/day) or a placebo. After 52 weeks, a few monkeys remained in observation for a six-week treatment-free period to evaluate the reversibility of any findings. The results showed that treatment with IVA337 caused no safety problems, changes in body or heart weight, or changes in red blood cell counts or creatinine.
Nor did the drug cause problems in other clinical parameters, as assessed by electrocardiography, ophthalmological examinations, hematology, clinical biochemistry and urinalysis, said the French pharmaceutical company.
“These results will be important for the end of Phase IIb discussions with regulatory authorities,” Inventa’s chief scientific officer and co-founder, Pierre Broqua, said in a press release. “Inventiva continues to deliver on its strategy to have IVA337 ready to enter into pivotal trials in NASH and SSc.”
Added toxicologist and regulatory consultant Jeri El-Hage: “We are impressed by the benign profile of IVA337, which does not show the side effects typically observed with thiazolidinediones or fibrates.”
The company will soon launch two carcinogenity studies in rodents to test IVA337 for 24 months. Once these studies are finished, Inventiva will have the data it needs to move the drug into Phase 3 studies and for regulatory filing sometime in mid-2018.
IVA337 is an anti-fibrotic drug with a unique mechanism of action: it activates all three alpha, gamma and delta peroxisome proliferator‐activated receptors (PPARs), or receptors that help control the fibrotic process. Both the FDA and the EMA have granted IVA337 orphan drug designation by to treat systemic sclerosis, which ensures Inventiva expedited regulatory activity and reduced fees, along with 10 years of commercial exclusivity.
In previous studies, IVA337 has been shown to have a good safety profile and to be well-tolerated. The drug has not had any reported effect on liver function, blood pressure, body weight or the volume of plasma in relation to red blood cells. Nor does it alter creatine phosphokinase (CPK), a muscle enzyme. IVA337 is currently being evaluated in Phase 2b clinical trials in both NASH (NCT03008070) and SSc (NCT02503644), with the company expecting results next year.
The purpose of the NASH clinical trial is to evaluate the efficacy and the safety of two daily doses of IVA337 (800mg, 1200 mg) for 24 weeks, versus placebo, in adult NASH patients with liver steatosis and moderate to severe liver inflammation without cirrhosis.