All primary and secondary outcome measures were met in a Phase IV study assessing Acthar Gel in patients with persistently active RA

Mallinckrodt Plc is reporting that all primary and secondary outcome measures were met in its Phase IV, multicenter study assessing the efficacy and safety of Acthar Gel (repository corticotropin injection, or RCI) in patients with persistently active RA who were previously treated with disease-modifying anti-rheumatic drugs (DMARDs) and corticosteroids . Encouraging topline data from the randomized, placebo-controlled, blinded, withdrawal phase of the study, as well as positive results from the open-label period of the study, were presented in a poster presentation on June 13 at the European Congress Of Rheumatology 2019 (EULAR) held June 12-15 in Madrid.

The Phase IV study poster "A Multicenter Study Assessing The Efficacy And Safety Of Repository Corticotropin Injection In Patients With Persistently Active Rheumatoid Arthritis" presented at EULAR 2019 is on the company's website. As previously announced, both parts of the multicenter study are now complete (open-label portion, n=259; randomized, placebo-controlled, blinded, withdrawal portion, n=154). Acthar Gel is FDA-approved as adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in RA, including juvenile RA (selected cases may require low-dose maintenance therapy).

Key Findings : Randomized, Placebo-Controlled, Blinded, Withdrawal Period : A number of measures were assessed to evaluate sustained improvement: Significantly more patients in the Acthar Gel group (62 percent) than in the placebo group (43 percent, P<0.05) had sustained LDA of <3.2 at Week 24, as assessed by the DAS28-ESR, a composite index that measures disease activity in patients with RA. Significantly more patients in the Acthar Gel group (86 percent) than in the placebo group (66 percent, P?0.05) had sustained low disease activity at Week 24, as defined by the Clinical Disease Activity Index (CDAI, Score ?10), a composite measure of disease activity in patients with RA. Significantly fewer patients in the Acthar Gel continuation group experienced cumulative disease activity flare rate at Week 24 (17 percent) than in the placebo group (30 percent, P<0.05). The proportion of patients who achieved ACR 20, 50, and 70 percent criteria3 at Week 24 were 91 percent, 75 percent and 47 percent, respectively, for the Acthar Gel group, and 84, 70 and 42 percent, respectively, for the placebo group. Adverse events (AEs) observed were consistent with those in previous trials of Acthar Gel. AEs (RCI n=33, PBO n=40) included diabetes mellitus (RCI n=1), increase in glycosylated hemoglobin (RCI n=1, PBO n=3), hyperglycemia (RCI n=4, PBO n=3) and hypertension (RCI n=4, PBO n=0).

Open-Label Period : The primary endpoint of the study was the proportion of patients reaching LDA by DAS28-ESR of <3.2 at 12 weeks. The open-label analysis showed there was a decrease in the mean DAS28-ESR scores from baseline through Week 12, with 63 percent of patients who completed the open-label period achieving the LDA target at Week 12. Acthar Gel was associated with significant improvements in DAS28-ESR and CDAI scores. Significant improvements in additional efficacy measures were seen at Week 12, including fatigue, physical function, swollen joints and tender joints. AEs observed were consistent with those in previous trials of Acthar Gel. AEs (n=38) included diabetes mellitus (n=1), increase in glycosylated hemoglobin (n=2), increase in liver function test (n=1), hyperglycemia (n=1) and hypertension (n=2). Three patients reported serious AEs (chest pain, pneumonia and craniocerebral injury). Bone turnover markers were assessed as an exploratory endpoint. Twenty-four patients discontinued the open-label period of the study.

Study Limitation: Sample bias may exist for the open-label phase of the ongoing study, and patients were aware that they were receiving Acthar Gel.Examiner bias may also exist as the patient had to reach low disease activity in order to enter the second phase of the study. The results cannot be solely attributed to Acthar Gel since patients were on different medications at the start of the trial and no washout periods were undertaken.