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Actemra gains FDA breakthrough status for systemic sclerosis, phase 2 data presented at EULAR
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Actemra has been granted breakthrough therapy designation by the FDA for the treatment of systemic sclerosis, and researchers presented data from a phase two study of Actemra in systemic sclerosis at the European League Against Rheumatism Annual European Congress of Rheumatology today.
A double-blind, placebo-controlled, phase 2, proof-of-concept study including 87 patients with active systemic sclerosis (SSc) based on 1987 American College of Rheumatology criteria was conducted. Eligible patients had disease duration of up to 5 years, a modified Rodnan skin score (mRSS) of 15 to 40 and elevated acute phase reactants.
Dinesh Khanna
“Both in vitro and animal data have suggested an important role of interleukin-6 (IL-6) in pathogenesis of fibrotic diseases. In addition, large observational cohorts in North America and Europe have shown that elevated IL-6 is associated with more severe disease, higher risk of progressive lung fibrosis and greater mortality,” Dinesh Khanna, MD, one of the FASSCINATE clinical trial investigators, told www.Healio.com/Rheumatology. “Based on these and clinical experience in patients, the study was launched to assess the efficacy and safety of tocilizumab in patients with early diffuse SSc.”
Forty-three patients were randomly assigned to receive 162 mg Actemra (tocilizumab, Genentech) subcutaneously, and 44 patients were assigned to receive 162 mg placebo. Baseline patient characteristics were similar between the two groups, according to the researchers.
The results at week 24 did not reach statistical significance on mRSS, although a favorable effect was observed; however, patients showed improvement at 48 weeks, with a greater change in mRSS score observed among patients who received tocilizumab (6.3) compared with placebo (2.8).
Forty percent of patients who received tocilizumab had a 20% improvement in mRSS from baseline compared with 27% of patients who received placebo. Twenty-one percent of patients who received tocilizumab improved by more than 40% compared with 7% of placebo patients, and 12% of tocilizumab patients improved by more than 60% compared with zero placebo patients; however, the results did not meet statistical significance, according to the researchers. Additionally, patient-reported outcomes were numerically higher in treated patients compared with those who received placebo, and improvement in Health Assessment Questionnaire scores of 0.22 or more was observed in 28% of tocilizumab-treated patients vs. those treated with placebo.
Also, when compared with placebo, a smaller number of patients treated with tocilizumab continued to show a decline in forced vital capacity at week 48, according to the researchers.
“One surprising exploratory result was the potential stabilization of lung function (a surrogate of lung fibrosis) in the tocilizumab group vs. continuing decline of approximately 25% patients in the placebo group over a 48 week period,” Khanna said. “As lung fibrosis is the leading cause of death in scleroderma, this preliminary finding is very exciting but needs to be validated in a larger trial.”
Adverse events included one death in the placebo groups and three deaths in the treatment group. One of the deaths, a fatal lung infection, was related to the study.
A phase three trial is expected to begin enrolling patients in the third quarter of this year. – by Shirley Pulawski
Reference:
Khanna D, et al. Paper #OP0054. Presented at: European League Against Rheumatism Annual European Congress of Rheumatology; June 10-13, 2015; Rome.
Disclosures: Khanna reports grants or research support from Actelion, Bayer, BMS, EMD Seerono, Gilead, InterMune, NIH/NIAMS, NIH/NIAID, Scleroderma Foundation, Pulmonary Hypertension Association and consults for Actelion, Bayer, BMS, EMD Serono, InterMune, Biogen Idec, Genentech/Roche, Cytori, Lycera, Sanofi-Aventis/Genzyme and GSK. Please see the full study for a list of all other authors’ relevant financial disclosures.