Mallinckrodt Presents New Data from 44-Week Open Label Extension Of Company-Sponsored H.P. Acthar® Gel Trial in Lupus

Researchers for Mallinckrodt plc

, a leading specialty biopharmaceutical company, today presented results from the 44-week open label extension (OLE) of its company-sponsored, two-part pilot study exploring the efficacy of H.P. Acthar® Gel (repository corticotropin injection) (RCI) in Systemic Lupus Erythematosus (SLE) patients with a history of persistently active disease. Acthar is approved by the U.S. Food and Drug Administration for use during an exacerbation or as a maintenance therapy in select patients with SLE. Study data were presented at the European League Against Rheumatism (EULAR) Annual Congress in London. The open label trial followed the 8-week, double-blind, placebo-controlled randomized phase of the study, results of which can be found on the Mallinckrodt website. All patients completing the first phase of the trial had the opportunity to volunteer to continue to the second phase, and all participants in the 44-week open label phase received Acthar. This included those who received placebo in the initial double-blind phase. "Taken together, the data from the two phases of this pilot study provide insight into the potential efficacy of Acthar's use as a treatment option in SLE patients who have persistent disease activity despite corticosteroid therapy," said Steven Romano, M.D., Senior Vice President and Chief Scientific Officer, Mallinckrodt. "The findings support the advancement of a well-powered, confirmatory trial in this lupus population, and Mallinckrodt plans to begin this company-sponsored study later this year." Study Measures, Goals and Outcomes Standardized disease activity measures were used over the entire 52 weeks of the study to evaluate the effect of RCI on SLE signs and symptoms, such as tender and swollen joints. Mallinckrodt's goal in conducting the open label extension was to explore three primary questions: How did study patients treated with RCI in the blinded, 8-week phase of the trial respond after the initial 8 weeks? When receiving RCI, did study patients treated with placebo in the blinded, 8-week phase of the trial experience similar results as those patients who received RCI in the blinded phase? Did any study patients taper or reduce their steroid use during the 44-week open label study? Data outcomes from the most recent phase of the study showed that: Study patients with persistently active SLE who continued on RCI throughout the 44-week OLE period maintained the reductions achieved in certain measures of disease activity during the blinded phase. Study patients who crossed over from placebo to Acthar in the OLE experienced improvements in certain measures of disease activity: By 12-16 weeks after initiating RCI for those patients who received placebo in the double-blind phase of the study, improvements in certain measures of disease activity were generally comparable to the improvements seen in patients who received RCI treatment in the blinded, 8-week phase of the trial. Approximately one third of subjects participating in the open label extension were able to taper exogenous corticosteroid dose by at least 50% over the 52 weeks of the study. "Systemic Lupus Erythematosus is a disease that can be very difficult to manage," said lead investigator Richard A. Furie, M.D., Chief of the Division of Rheumatology, Northwell Health, Great Neck, New York. "It is encouraging to see clinically meaningful, longer-term results from this pilot study of Repository Corticotropin Injection, and I look forward to future data readouts." Study Limitations Limitations of this pilot study included the small sample size as well as lack of blinding and lack of a comparator group, both of which are elements associated with an open label design. These results may not be fully representative of outcomes in the overall patient population. Most patients were on multiple therapies. The clinical outcomes may not be solely attributable to Acthar. Study Details The Mallinckrodt-sponsored study was titled: "A two-part study exploring the efficacy, safety, and pharmacodynamics of Acthar in systemic lupus erythematosus patients with a history of persistently active disease." Any study patient who completed the 8-week, double-blind, placebo-controlled randomized phase of the study, whether randomized to RCI or placebo, was eligible to enroll in the 44-week open label phase of the study. Of the 38 patients randomized in Phase 1, all 33 patients who completed the initial 8-week pilot study chose to continue in the 44-week OLE phase of the study, with 20 patients completing the full 44 weeks. The initial Acthar dose in the open label extension study was based on study drug regimen at the completion of the double-blind phase of the trial. Acthar dose adjustment was allowed with the goal of a stable Acthar regimen by week 20, but no later than week 28. Steroid dose adjustment was not allowed until stable Acthar regimen was achieved (weeks 20-28). Steroid taper was encouraged but not required after stable RCI regimen was achieved. Taper of other immunosuppressants was allowed after attempts at steroid taper. There were no unexpected adverse events (AEs). Five of the 33 patients withdrew from the trial due to AEs that were thought to be potentially related to study medication during the open label extension phase. The abstract and the poster are currently available on the Mallinckrodt website.