Idorsia to advance cenerimod into phase III development for treatment of patients with systemic lupus erythematosus.

The CARE study equally randomized 427 adult patients with SLE on background therapy, to cenerimod (0.5, 1, 2, 4 mg) or placebo. Patients randomized to cenerimod 4 mg showed an improvement in the modified-Systemic Lupus Erythematosus Disease Activity Index-2000 (mSLEDAI-2K) score compared to placebo from baseline to Month 6 (p=0.029). However, this result did not reach statistical significance in the formal testing strategy when adjusting for multiplicity of tests for the four doses against placebo. The increasing improvement compared to placebo in mSLEDAI-2K with cenerimod 4 mg over time was further supported by a consistent improvement across several patient sub-populations, particularly in patients with more severe disease activity; on Systemic Lupus Erythematosus Responder Index 4 (SRI-4); and was associated with an effect on several biological markers of disease activity.

Cenerimod was well tolerated in all treatment groups such that similar rates of AEs were reported across all treatment groups, 0.5 mg: 49.4%; 1 mg: 64.7%; 2 mg: 59.3%; 4 mg: 58.3%; placebo: 54.7%, during six months of treatment. The most frequent treatment emergent adverse events reported over 5% incidence in any group and higher than placebo during six months of treatment were: abdominal pain, headache, and lymphopenia.

A reversible decrease in lymphocyte count is linked to the mechanism of action of cenerimod and as expected lymphopenia was more often seen in patients treated with the higher 2 mg and 4 mg doses. Importantly, there was no increased rate of infections compared to placebo: 0.5 mg: 23.5%; 1 mg: 11.8%; 2 mg: 19.8%; 4 mg: 20.2%; placebo: 18.6%.

While S1P1 receptor modulators are known to transiently affect heart rate (HR) at initiation of therapy, to potentially decrease pulmonary function and increase blood pressure, cenerimod showed a transient, asymptomatic, dose-dependent decrease in HR at first dose; over the 6 months of treatment, effects on pulmonary function could not be discerned from placebo, and there was minimal to no effect on blood pressure.

Guy Braunstein, MD and Head of Global Clinical Development of Idorsia, commented: “I’m very pleased to see that the results with 4 milligrams of cenerimod, particularly the safety profile, have confirmed the data generated in the proof of concept study. We have seen a large effect on biomarkers of disease activity, and this has translated into improvement on multiple clinical measures. The six months of treatment results have provided us with the information we need to design our Phase III program in SLE and to discuss with health authorities, including the patient population, the optimal dose and endpoints. I also look forward to seeing the results of the next treatment period of CARE, where patients will continue to receive blinded treatment for a further six months. A lot can be learned from the long-term treatment data, further characterizing the efficacy, safety and tolerability of cenerimod.”

The company will now fully analyze the data, including patient reported outcomes showing the effect of cenerimod on quality of life measures, and will discuss the Phase III program with health authorities as soon as possible. The investigation of cenerimod for the treatment of SLE has been designated as a “fast-track” development program by the FDA. This designation is intended to promote communication and collaboration between the FDA and pharmaceutical companies for drugs that treat serious conditions and fill an unmet medical need.