medwireNews: Romilkimab could significantly improve skin fibrosis in people with early diffuse cutaneous systemic sclerosis (dcSSc), results of a phase 2 proof-of-concept study suggest.
Yannick Allanore (Paris Descartes University, France) and co-investigators say that despite “strong evidence […] that interleukin (IL)-4 and IL-13 are involved in the pathology of SSc,” until now, “no therapies directed against these cytokines have been developed for the treatment of this disease.”
Romilkimab (SAR156597), however, “is an engineered, humanised, bispecific immunoglobulin-G4 antibody that binds and neutralizes IL-4/IL-13 making it ideal for exploration in fibrosis,” the researchers explain.
They tested its efficacy and safety in 97 adults (mean age 50 years, 79% women) with dcSSc (mean duration 21 months) who had a mean baseline modified Rodnan skin score (mRSS) of 20.6 points, with or without immunosuppressive background therapy.
During 24 weeks of treatment, mRSS fell by a least squares (LS) mean of 4.76 points in the 48 patients randomly assigned to receive weekly subcutaneous romilkimab 200 mg.
By comparison, the LS mean reduction in mRSS was significantly smaller among the 49 patients randomly assigned to receive placebo, at 2.45 points, resulting in a significant treatment difference of 2.31 points.
Individuals in the romilkimab group also experienced a numerically smaller LS mean decline in forced vital capacity and diffusing lung capacity for carbon monoxide corrected for hemoglobin than those in the placebo group between baseline and week 24, at 10 mL versus 80 mL and 0.12 mmol/minute per kPa versus 0.27 mmol/minute per kPa, respectively.
In addition, an exploratory analysis using the EQ-5D-5L quality of life index showed that individuals treated with romilkimab experienced an improvement of 0.07 points whereas those treated with placebo had no change in their score from baseline, resulting in a statistically significant difference between the two groups.
The majority of patients (80–84%) in both groups experienced at least one treatment-emergent adverse event (AE) but “most were mild or moderate in intensity,” Allanore et al remark.
There were no treatment-related deaths, but two patients in the placebo group had a cardiovascular treatment-emergent serious AE (one cardiac failure, one cardiomyopathy) compared with none in the romilkimab group. Two patients in the romilkimab group and one in the placebo group permanently discontinued treatment as a result of esophageal stenosis, scleroderma renal crisis, and cardiomyopathy, respectively.
Writing in the Annals of the Rheumatic Diseases, Allanore and co-authors conclude that their findings “are consistent with a meaningful benefit of romilkimab on skin involvement but should be interpreted with caution in a phase II study.”
They add that the data now “require confirmation with a longer and more comprehensive phase III study to determine clinical relevance.”
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Ann Rheum Dis 2020; doi:10.1136/annrheumdis-2020-218447