#AAN2018 – H.P. Acthar Gel Shows Promise as Therapy to Delay Progression of ALS

H.P. Acthar Gel, an experimental injectable therapy, may help delay progression of amyotrophic lateral sclerosis (ALS), a new analysis reveals.

The data is scheduled to be presented at the 70^th annual meeting of the American Academy of Neurology (AAN) in Los Angeles, April 21–27, in a presentation titled, “Post hoc analysis using PRO-ACT database to evaluate Repository Corticotropin Injection (H.P. Acthar® Gel) as a potential treatment for ALS.” The presentation is part of a session titled General Neurology.

Researchers explored the effects of H.P. Acthar Gel (repository corticotropin injection, or RCI) on disease progression in adults with ALS. The therapy, sold under the brand name Acortan (among others) is used in several inflammatory diseases, including multiple sclerosis and systemic lupus erythematosus.

The therapy is under investigation for ALS and received U.S. Food and Drug Administration (FDA) fast track designation and orphan drug status.

H.P. Acthar Gel, developed by Mallinckrodt, contains a highly purified preparation of the adrenocorticotropic hormone (ACTH) and may have anti-inflammatory, neuroprotective, and neuroregenerative effects that could delay or even halt ALS progression.

ACTH stimulates the release of naturally produced steroid hormones by the adrenal gland, located on top of the kidneys, such as cortisol, corticosterone, and aldosterone. These steroid hormones are involved in the regulation of many biological functions, including immune response, metabolism, and blood pressure.

Researchers used data from two studies — a pilot study of RCI and the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database — to assess the impact of the therapy on ALS progression.

In the pilot study, ALS patients were randomized to receive subcutaneous injections of H.P. Acthar Gel (16 U, 0.2 mL) or a volume-matched placebo once daily for 36 weeks. In total, 43 ALS patients received H.P. Acthar Gel.

Following the 36 weeks, participants either stop the treatment or continue daily H.P. Acthar Gel injections during a 48-week open-label extension phase.

The study main outcome is to assess the changes from baseline up to the 36 weeks in the ALS Functional Rating Scale (ALSFRS). Researchers analysed this parameter every month. Additional parameters evaluated include decline in pulmonary function test scores, survival, and occurrence of adverse events.

Researchers also performed a case-matched control analysis using placebo-treated patients from PRO-ACT. H.P. Acthar Gel-treated patients were paired with up to three patients from PRO-ACT using seven variables associated with disease progression.

At baseline, the mean ALSFRS scores were 27.8 in the H.P. Acthar Gel-treated group and 27.2 in the PRO-ACT control group.

The case-match control analysis revealed that after 36 weeks of treatment, the ALSFRS scores of H.P. Acthar Gel-treated patients declined by a mean of 4.3  points and by 6.6 points in the control group – a statistically significant difference.

For the post-hoc analysis (looking at the data after a study has been concluded), researchers generated a prediction algorithm that used the baseline characteristics to generate a 36-week estimate of patients’ response. They compared it to the changes in ALSFRS scores from the H.P. Acthar Gel pilot study.

For the 21 patients who completed the study, the changes in progression in ALSFRS scores were smaller, but still similar to that predicted by the algorithm.

Overall, these results “suggest potential RCI efficacy in the treatment of ALS and support further study of RCI for ALS in controlled trials,” researchers concluded.