To assess the efficacy of paquinimod, a new immunomodulatory small molecule, in a murine lupus model, and to evaluate its pharmacokinetics and tolerability in systemic lupus erythematosus (SLE) patients at doses predicted to be efficacious and safe and determine the maximum tolerated dose.

The efficacy of paquinimod was studied in lupus‐prone MRL‐lpr/lpr mice and compared with that of established SLE treatments. Dose‐response data and pharmacokinetic data were used to calculate effective and safe clinical doses of paquinimod. The pharmacokinetics and tolerability of paquinimod were evaluated in a phase Ib double‐blind, placebo controlled, dose‐ranging study in which cohorts of SLE patients received daily oral treatment for 12 weeks.

Paquinimod treatment resulted in disease inhibition in MRL‐lpr/lpr mice, comparable to that obtained with prednisolone and mycophenolate mofetil; prominent effects on disease manifestations and serologic markers and a steroid‐sparing effect were observed. In patients with SLE, the pharmacokinetic properties of paquinimod were linear and well suitable for once‐daily oral treatment. The majority of the adverse events (AEs) were mild or moderate, and transient. The most frequent AEs were arthralgia and myalgia, reported with the highest dose levels of paquinimod (4.5 mg/day and 6.0 mg/day). At the 4.5 mg/day dose level and higher, some AEs of severe intensity and serious adverse events were reported.

Paquinimod effectively inhibited disease and had a steroid‐sparing effect in experimental lupus. Results from preclinical models together with pharmacokinetic data were successfully translated into a safe clinical dose range, and doses of up to 3.0 mg/day were well tolerated in the SLE patients. Taken together, the promising combined data from a murine model and human SLE support the future clinical development of paquinimod.