The phase 2b trial of the repository corticotropin injection (Acthar Gel) in amyotrophic lateral sclerosis was halted due to data and safety board concerns of the potential risk of pneumonia.
Steven Romano, MD, executive vice president, chief scientific officer, Mallinckrodt
Steven Romano, MD
A phase 2b clinical trial, dubbed PENNANT, meant to assess the safety and efficacy of a repository corticotropin injection (Acthar Gel) in the treatment of amyotrophic lateral sclerosis (ALS) has been stopped based on a recommendation by the study’s independent data and safety monitoring board, Mallinckrodt announced.
The board specifically cited the concern related to pneumonia, which occurred at a rate higher than that of the placebo group. Due to the consequences of pneumonia for the ALS patient population, as well as a mention of other adverse events (AEs) related to the condition, 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," said Steven Romano, MD, executive vice president, chief scientific officer, Mallinckrodt, in a statement.
The study (NCT03068754) enrolled patients aged 18 to 75 years with ALS and a symptom onset, defined as first muscle weakness or dysarthria, more than 2 years prior to the screening visit. Patients were then randomized 2:1 to either subcutaneous Acthar Gel 0.2 mL (16 units) daily or matching placebo 0.2 mL daily, for a total of 36 weeks.
Additionally, the data and safety monitoring board made note of the proportion of patients achieving the primary end point, completion to Week 36, “precludes a definitive determination of a treatment effect,” Mallinckrodt stated. This lack of an efficacy signal for the cohort combined with the higher risk of pneumonia was what ultimately informed the board's recommendation.
"Though the probability of success for the ALS population was acknowledged as being low, this study was initiated based on compelling analyses carried out following the completion of a small pilot study and we were hopeful it would have translated into a benefit for this group of patients in great need of effective therapies,” Romano said. “We thank the DSMB, the investigators and the patients who participated in the study."
Notably, Mallinckrodt stated that there will be no impact from this decision 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 upward of $500M to the development of the Acthar Gel.
Currently, the product is FDA approved for the treatment of 19 indications, including as an adjunctive therapy for short-term administration in rheumatoid arthritis, including juvenile rheumatoid arthritis; for treatment of symptomatic sarcoidosis; for infantile spasms; for maintenance therapy in selected cases of systemic lupus erythematosus; for exacerbations of multiple sclerosis; inducing diuresis in nephrotic syndrome without uremia; and others.
The common AEs with the Acthar Gel 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.
1. 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 July 22, 2019.