Acthar Gel (repository corticotropin injection) leads to significant improvements after two months of use in people with multiple sclerosis (MS) still having acute relapses despite treatment, and who failed to respond to other high-dose corticosteroids, topline data from an observational study show.
The gel’s developer, Mallinckrodt Pharmaceuticals, also announced that its OPTIONS trial, evaluating the safety of Acthar Gel in relapsing-remitting MS (RRMS) patients who have not responded to treatment with high-dose steroids — a standard of care treatment — is now about half enrolled.
These findings were presented in two posters at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2020 that ran in Florida on Feb. 27–29.
Acthar Gel is currently approved by the U.S. Food and Drug Administration (FDA) for several indications, including the treatment of acute MS flares (disease exacerbations) in adults with frequent and recurring relapses.
The gel consists of adrenocorticotropic hormone (ACTH), and can be injected under the skin (subcutaneously) or into the muscle (intramuscular). It works by enhancing the production of steroids in the body to reduce inflammation and more rapidly resolve a disease relapse.
In MS, treatment that can effectively prevent a relapse is critical for minimizing disability.
Mallinckrodt conducted an observational registry study (NCT02633033) to monitor the course of MS, and to document relapses and the recovery process, in a group of MS patients treated with Acthar Gel.
Its findings were presented at ACTRIMS in the poster “Topline Results Of A Prospective Observational Registry Of Repository Corticotropin Injection For The Treatment Of Multiple Sclerosis Relapse.”
The study’s primary goal was to assess the effect of Acthar Gel on symptoms associated with MS relapses after two months of treatment, based on the MSIS-29 impact scale, a tool that measures the impact of MS in physical and psychological aspects from a patient’s perspective.
In the MSIS-29 physical subscale, participants rate 20 physical disease symptoms from one (no impact) to five (extreme impact). Higher scores represent a greater impact of disease symptoms on day-to-day life.
Patient’s physical symptoms were also evaluated using the Expanded Disability Status Scale (EDSS, a scale that measures the degree of disability), and the Clinical Global Impression of Improvement (CGI-I) scale. CGI-I scores range from one (considerably improved) to seven (considerably worse).
It enrolled 145 adults (mean age of 47) in the U.S., who had MS for about 10 years. Eighty-two completed the study.
More than half of the participants (60%) had a history of intolerance or poor response to treatment with high-dose corticosteroids, and 58.4% reported having had at least one relapse in the two years before enrolling in the study.
The most common disease-modifying therapies (DMTs) used by patients during this study included: Biogen’s Tecfidera (dimethyl fumarate; 20%), and Tysabri (natalizumab; 18.4%); followed by Aubagio (teriflunomide; 11.2%) marketed by Sanofi Genzyme; Copaxone (glatiramer acetate; 8.8%) marketed by Teva; Ocrevus (ocrelizumab; 8.0%) by Genentech; Gilenya (fingolimod; 6.4%) marketed by Novartis; and interferon beta-1a (5.6%).
Topline results showed that people given Acthar Gel had a significant reduction in their symptoms after two months of treatment. These improvements were still seen at month six.
Specifically, patients treated with Acthar Gel showed a decrease in the MSIS-29 physical subscale of 7.99 at two months, and 9.64 at six months, from a baseline (study start) score of 55.69 .
Physicians also reported significant improvements in patients’ physical symptoms, as shown by a decrease in the mean EDSS scores after two months — from 3.92 (at baseline) to 0.37. At six months, the EDSS score was still significantly lower (0.45) than at the trial’s start (3.92).
The CGI-I scores also indicated a significant improvement at two months in more than half of the patients (63.4%). Once again, these improvements were sustained in 61.4% of patients at six months.
Regarding safety, a total of 83 adverse events were reported in 35 patients (28.0%). Serious adverse events occurred in 11 patients (8.8%).
Overall, the results “support the efficacy and tolerability of RCI [repository corticotropin injection; Acthar Gel] as a treatment for MS relapse,” the researchers wrote.
In the second poster, “Study Design Of The Randomized, Double-blind, Placebo-controlled OPTIONS Study Of Repository Corticotropin Injection For Acute Exacerbations Of RRMS,” researchers described the characteristics of 32 patients now enrolled in the OPTIONS (NCT03126760) trial, which is evaluating the efficacy and safety of Acthar Gel in adults with RRMS who have not responded to treatment with high-dose steroids.
OPTIONS aims to enroll 66 people, who will be randomized to subcutaneous injections of Acthar Gel (1 mL per day, corresponding to 80 Units) or a matching placebo for 14 days.
The study’s main goal is to assess the response rate based on EDSS at 42 days after treatment. Response is defined as the percentage of patients with an improvement in EDSS scores of at least one point (for those with a EDSS score equal or lower than 5.5 at the trial’s start), or at least 0.5 points (for those with an EDSS score higher than 5.5).
Additional parameters include patients’ scores in the MSIS-29 impact scale and CGI-I scale. Safety will also be assessed.
The 32 adults enrolled (mean age, 42.2) have been living with MS for an average of 13.7 years. The majority (78.1%) are women, and Caucasian (84.4%), with a mean EDSS score at the trial’s start of 3.91.
These people have had treated with Copaxone, Aubagio, Lemtrada, Tecfidera, Gilenya, or interferon beta-1b.
Researchers hope that data from the OPTIONS trial will “support RCI as an effective treatment for acute exacerbations of RRMS in patients with inadequate response to high-dose steroids,” they wrote.
OPTIONS is recruiting across multiple clinical sites in the U.S. More information can be found here.
“These studies underscore our commitment to patients with difficult-to-treat MS relapse who continue to have symptoms and disease exacerbations that don’t resolve with standard therapy,” Tunde Otulana, MD, senior vice president and chief medical officer at Mallinckrodt, said in a press release.
The two studies presented at ACTRIMS “seek to better understand this patient population and Acthar Gel’s potential role in MS relapse,” Otulana concluded.
