Data presented by researchers for Mallinckrodt plc, a leading specialty biopharmaceutical company, suggest that H.P. Acthar® Gel (repository corticotropin injection) reduces certain measures of disease activity in patients with persistently active Systemic Lupus Erythematosus (SLE) who are receiving corticosteroid therapy. The pilot study data were presented at a poster session during the 2015 American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals (ARHP) Annual Meeting in San Francisco being held Nov. 7-11, 2015.
"Acthar demonstrated clinically relevant improvement in signs and symptoms of lupus in patients who need an alternative therapy for persistent symptoms," said Steven Romano, M.D., Senior Vice President and Chief Scientific Officer, Mallinckrodt Pharmaceuticals. "This is one of many studies Mallinckrodt is pursuing related to Acthar. We are encouraged by the results of this small study, and the potential Acthar may hold for patients with persistently active SLE."
Acthar is approved by the U.S. Food and Drug Administration (FDA) for use during an exacerbation or as a maintenance therapy in select patients with SLE. For this pilot study, while certain secondary endpoints of the study showed positive results, the primary endpoint was not met.
"Systemic Lupus Erythematosus can be very difficult to manage, and there is an urgent need for additional treatment options," said lead investigator Richard A. Furie, M.D., Chief of the Division of Rheumatology, Hofstra North Shore LIJ School of Medicine, Great Neck, New York. "These data are important because they offer evidence of the efficacy of Acthar as a treatment alternative for patients with SLE."
The company-sponsored study, titled "Repository Corticotropin Injection (H.P. Acthar Gel) Attenuates Disease Activity in Patients with Persistently Active Systemic Lupus Erythematosus (SLE) Requiring Corticosteroids," was an eight-week, double-blind, randomized, placebo-controlled study that assessed the clinical efficacy of repository corticotropin injection (RCI) in 38 patients with persistently active SLE involving skin and/or joints, despite moderate dose corticosteroids.
In the eight-week study, subjects were randomized two-to-one with Acthar vs. placebo to receive RCI 40 units subcutaneously every day, RCI 80 units subcutaneously every other day, or a volume-matched placebo gel. Assigned dosing was maintained for the first four weeks then tapered to a twice weekly maintenance dose over the last four weeks. The primary endpoint explored the effects of RCI on the skin and joint sub-scores of the hybrid SLE Disease Activity Index (hSLEDAI), while secondary objectives evaluated effects on total hSLEDAI, British Isles Lupus Assessment Group-2004 (BILAG), Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity, and tender and swollen 28-joint count scores. A post-hoc exploratory endpoint included the SLE responder index (SRI), a composite measure of disease activity.
An open-label extension of this study, exploring the tolerability, steroid-sparing effects, and impact of Acthar on long-term disease control, is ongoing and near completion.
Primary Endpoint Results
The primary endpoint of response (defined by complete resolution of skin or joint activity by hSLEDAI with no new organ system disease by BILAG) was not met.
Certain Secondary Endpoints Results
The addition of RCI to standard of care led to significant improvement in certain measures of disease activity, including total hSLEDAI score, total BILAG score, CLASI activity score, tender and swollen joint count, and SRI. Mean hSLEDAI scores at baseline were 9.8±2.1, 8.7±2.9, 11.3±3.3, and 10.0±3.3 in the combined placebo, RCI 40, RCI 80, and combined RCI groups, respectively (mean ±SD).
RCI led to significant improvement in secondary efficacy endpoints compared with placebo, including reduction in total hSLEDAI, BILAG, and CLASI Activity scores, decreased tender and swollen joint count, and increased proportion of subjects achieving response as defined by SRI. Significant improvements in disease activity were seen at weeks six and weeks eight after the initiation of RCI therapy.
There were no significant differences in the incidence of treatment-emergent adverse events between groups. 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. Acthar has not been formally studied in combination with other commonly used therapies for SLE.