Dr Steve RomanoSteven Romano, MD
Positive top-line data from an observational registry dataset assessing treatment patterns and clinical response to Mallinckrodt’s repository corticotropin injection (Acthar Gel) have been announced, noting that the treatment is associated with a reduction in the impact of disease exacerbations in those with multiple sclerosis (MS).1

The treatment, which is approved by the FDA for the treatment of acute MS relapses among other indications, showed statistically significant results for every efficacy end point assessed, including the primary end point, measured as change in symptom impact on the MS Impact Scale, version 1 (MSIS 29v1). Mallinckrodt also announced that the data would be shared at an upcoming medical meeting.

"Mallinckrodt is committed to generating data that helps clarify to the prescriber those patients appropriate for treatment with Acthar Gel to manage MS relapses," Steven Romano, MD, executive vice president and chief scientific officer, Mallinckrodt, said in a statement. "The registry evaluated the effect of Acthar Gel in prospectively defined patients who were treated with Acthar Gel following an acute relapse.”

The registry was designed to explore outcomes at 2 months and the maintenance of effect at 6 months, as well as patient characteristics. The average patient age was 47 years, with a mean duration of disease of 10 years. All told, 60% of patients reported a history of insufficient treatment response, intolerance, or intravenous access problems with prior high-dose corticosteroid therapy, while 58% reported ≥1 MS relapses in the 2 years prior to enrollment.

The data suggest that those treated with the corticotropin injection had significant improvements in symptoms associated with MS relapse at the 2-month mark, a response that was sustained at 6 months. As well, clinicians noted an improvement in physical symptoms in patients treated with Acthar Gel, based on the Expanded Disability Status Scale (EDSS) scores.

“In addition, we look forward to Mallinckrodt's ongoing, randomized, double-blind, placebo-controlled OPTIONS study, which we anticipate will provide data on some of the more difficult-to-treat MS patients in the future," Romano said.

Adverse events (AEs) were consistent with those in previous trials of the gel, which are considered similar to those of corticosteroids. These include fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain.

The therapy has also been assessed in the treatment of amyotrophic lateral sclerosis (ALS), in which a phase 2b clinical trial, dubbed PENNANT, was recently halted due to recommendation by the study’s independent data and safety monitoring board. Specifically, a concern related to pneumonia was cited, as it occurred at a rate higher than that of the placebo group. Due to the consequences of pneumonia for the ALS patient population, the company noted that it agreed to permanently halt the trial in the interest of patient safety.

"Mallinckrodt's primary focus is on the safety of patients and, while ALS patients are among those most in need of new therapies and treatment options, we believe this is the right decision. It is critical to stress, however, that these findings do not impact the current positive benefit/risk profile of Acthar for use in current on-label indications," Romano said in a statement in July.2

Notably, Mallinckrodt stated that there would be no effect on other ongoing trials of its repository corticotropin injection formulation, as the company is “committed to responsible and ethical scientific exploration” aimed at treating critical conditions. Thus far, the company has invested upwards of $500M to the development of the Acthar Gel.
REFERENCES
1. Mallinckrodt Announces Positive Top-Line Findings from its Observational Registry Assessing Relapse Recovery in Multiple Sclerosis Relapse Patients Treated with Acthar® Gel (Repository Corticotropin Injection) [press release]. Staines-Upon-Thames, UK: Mallinckrodt; Published October 1, 2019. prnewswire.com/news-releases/mallinckrodt-announces-positive-top-line-findings-from-its-observational-registry-assessing-relapse-recovery-in-multiple-sclerosis-relapse-patients-treated-with-acthar-gel-repository-corticotropin-injection-300928259.html. Accessed October 3, 2019.
2. Mallinckrodt Halts Phase 2B Trial Investigating the Use of Acthar® Gel (Repository Corticotropin Injection) in Amyotrophic Lateral Sclerosis (ALS) [press release]. Staines-Upon-Thames, UK: Mallinckrodt; Published July 16, 2019. biospace.com/article/releases/mallinckrodt-halts-phase-2b-trial-investigating-the-use-of-acthar-gel-repository-corticotropin-injection-in-amyotrophic-lateral-sclerosis-als-. Accessed October 3, 2019.