Mallinckrodt Pharmaceuticals has shut down its Phase 2b PENNANT clinical trial assessing the effectiveness and safety of H.P. Acthar Gel, an experimental injectable therapy for amyotrophic lateral sclerosis (ALS).
The reason for this decision was an increased incidence of pneumonia among ALS patients receiving H.P. Acthar Gel compared to placebo-treated patients in a control group. Enrollment will cease immediately, and patients who had been taking the drug will be tapered off the treatment.
Mallinckrodt, developer of H.P. Acthar Gel, followed the recommendation of the independent Data and Safety Monitoring Board (DSMB), which was set up to oversee the study by reviewing semi-blinded information, following industry best practice guidelines.
“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,” Steven Romano, MD, executive vice president and chief scientific officer at Mallinckrodt, said in a press release.
The PENNANT trial (NCT03068754), which was underway at multiple sites in the United States, Canada, Mexico, and South America, was intended to recruit 210 ALS patients age 18 to 75 who had onset of symptoms within two years of screening.
Participants were randomized to receive under-the-skin injections of H.P. Acthar Gel (0.2 mL), or a volume-matched placebo once daily for 36 weeks.
The study’s main objective was to assess patients’ changes using the ALS Functional Rating Scale (ALSFRS) from the start of the trial up to 36 weeks. Additional parameters included decline in pulmonary function test scores, survival, and occurrence of adverse side effects.
The number of patients in the PENNANT trial who completed the 36 weeks treatment was not enough to assess signs of effectiveness and, due to the potential risk for pneumonia, the DSMB’s recommendation was to halt the trial.
H.P. Acthar Gel is made of a highly pure preparation of adrenocorticotropic hormone (ACTH) and may help delay ALS progression due to its anti-inflammatory and neuroprotective properties.
ACTH stimulates the release of natural steroid hormones, such as cortisol, corticosterone, and aldosterone. These steroid hormones, released by the adrenal gland, regulate several key functions, including immune response, metabolism, and blood pressure.
Prior clinical data showed that H.P. Acthar Gel could help delay progression of ALS. After 36 weeks of treatment, in H.P. Acthar Gel-treated patients the ALSFRS scores declined by a mean of 4.3 points and by 6.6 points in the control group, a statistically significant difference.
“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. We thank the DSMB, the investigators and the patients who participated in the study,” Romano said.
H.P. Acthar Gel is under investigation for ALS, but the therapy, sold under the brand name Acortan (among others), is used in several inflammatory diseases, including multiple sclerosis and systemic lupus erythematosus. These findings have no impact on the therapy’s effectiveness in these settings.
“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 added.