A Comparison of the Safety/Tolerability and Pharmacodynamics of Acthar Gel and Methylprednisolone with Regimens Utilized for the Treatment of MS Exacerbations (P2.207)

OBJECTIVE: To compare the pharmacodynamics (PD) and safety profile of subcutaneous H.P. Acthar Gel ® (Acthar) to intravenous methylprednisolone (IVMP) in healthy subjects, using dosage regimens commonly employed for treatment of multiple sclerosis (MS) exacerbations. BACKGROUND: Both Acthar and IVMP are used to treat MS exacerbations. This study was conducted to determine if a 5-day regimen of Acthar was associated with improved safety, tolerability and PD as compared with IVMP. DESIGN/METHODS: This multiple-dose, randomized, open-label, crossover study evaluated 18 healthy male and female subjects (9 per treatment sequence). Subjects received either Acthar (80U, SC) or IVMP (1g) daily for 5 days, and were then crossed over to the other medication after a 30-day washout to complete the treatment sequence. Outcomes evaluated included cortisol response, total corticosteroid exposure, changes in total leukocyte (WBC) counts and WBC subpopulations, blood glucose and blood pressure, and adverse events (AEs). Preliminary analyses included the first treatment sequence (with a subset of 4 subjects for the steroid-exposure assessment and flow cytometry). RESULTS: Preliminary results suggest that more drug-related AEs occurred with IVMP than Acthar. Importantly, total steroid-exposure was greater for IVMP than Acthar, demonstrated by a serum cortisol-equivalent exposure ratio (Acthar:IVMP) of 0.04±0.03 (Day 5). Additionally, leukocytosis was attenuated following Acthar administration compared with IVMP, and flow cytometry data suggested this was due to a less profound increase in circulating neutrophils. Acthar was also associated with less lymphopenia than IVMP, with greater recovery of lymphocyte counts by Day 5. Effects of Acthar and IVMP on mean arterial pressure and blood glucose were relatively small compared to pre-treatment baseline, and did not appear to vary between treatments. CONCLUSIONS: These preliminary data indicate that this Acthar regimen used to treat MS exacerbations resulted in fewer drug-related AEs and Disclosure: Dr. Bell has received personal compensation for activities with Questcor Pharmaceuticals as an employee, and Array BioPharma as an employee. Dr. Vincent has received personal compensation for activities with Questcor Pharmaceuticals. Dr. Hammock has received personal compensation for activities with Questcor Pharmaceuticals. Dr. Welch has received personal compensation for activities with Questcor Pharmaceuticals. Dr. Welch has received research support from Questcor Pharmaceuticals. Dr. Chung has received personal compensation for activities with Questcor Pharmaceuticals. Dr. Chung holds stock and/or stock options in Questcor Pharmaceuticals. Dr. Nyberg has received personal compensation for activities with Questcor Pharmaceuticals. Dr. Becker has received personal compensation for activities with Questcor Pharmaceuticals. Dr. Becker holds stock and/or stock options in Questcor Pharmaceuticals. Dr. Young has received personal compensation for activities with Questcor Pharmaceuticals. Dr. Young holds stock and/or stock options in Questcor Pharmaceuticals which sponsored research in which Dr. Young was involved as an investigator. Dr. Young holds stock and/or stock options in LifeScience Plus.