The Clinigen Group’s ALS treatment is currently being investigated in a phase 2 trial that is expected to conclude in September 2021.
Clinigen Group announced that the FDA has granted orphan drug designation to aldesleukin, the company’s investigational agent for the treatment of amyotrophic lateral sclerosis (ALS).1
The basis of the decision is built on previous studies that have shown that treatment with aldesleukin can decrease levels of regulatory T-cells (Tregs) in patients with ALS. Tregs are associated with increased disease severity and are predictive of disease progression and survival. Additionally, it has been shown to enhance Treg function in inflammatory and auto-immune conditions at doses significantly lower than those used in oncologic indications.
“The orphan drug designation issued by the FDA recognizes the potential of aldesleukin as a possible valuable new treatment for patients with ALS where there is a significant unmet need within the disease,” Shaun Chilton, group chief executive officer of Clinigen, said in a statement.
Previous studies have demonstrated the correlation between Tregs and disease severity and progression in those with ALS. Recently published data showed that in peripheral blood, Tregs subtypes presented a shift towards pro-inflammatory Th1 and Th17 cells whereas anti-inflammatory Th2 and T regulatory cells were decreased. Correlation analysis also showed moderate negative correlations between Th1 and Th17 to the ALS Functional Rating Scale revised (ALSFRS-R) and to forced vital capacity.2
Aldesleukin is a recombinant interleukin 2 (IL-2) currently marketed under the brand name Proleukin. At conventional doses, it is used in the treatment of kidney cancer that has spread to another part of the body.
The agent is currently being studied in the phase 2 Modifying Immune Response and OutComes in ALS (MIROCALS) trial (NCT03039673). The randomized, double-blind, placebo-controlled, proof of concept clinical study will focus on the efficacy and safety of aldesleukin in 304 patients with ALS. The primary outcome of the study is time to death from date of randomization to date of death across the 18-month stretch. Other aims of the trial include shortening future trials duration in ALS using an early drug responding surrogate marker of disease activity, establishing the proof of mechanism of the tested drugs, and to identify drug responder status.
Patients within the study will be treated with riluzole for a period of 3 months prior to inclusion and randomization and will continue the same treatment throughout the 18 months of follow-up. Each treatment course of aldesleukin will last 5 days, with 1 subcutaneous injection per day for 5 consecutive days, repeated every 4 weeks over the 18-month treatment period.
Results from MIROCALS are expected to be published when the trial concludes in September 2021.
1. Clinigen granted orphan drug designation by the FDA for aldesleukin in the treatment of amyotrophic lateral sclerosis (ALS)[news release]. Yardley, PA. Clinigen. Published July 13, 2020. Accessed July 16, 2020. clinigengroup.com/news/news-container/2020/clinigen-granted-orphan-drug-designation-by-the-fda-for-aldesleukin-in-the-treatment-of-amyotrophic-lateral-sclerosis-als/
2. Mengmeng J, Gunther R, Akgun K, Hermann A, Ziemssen T. Peripheral prioinflammatory Th1/Th17 immune cell shift is linked to disease severity in amyotrophic lateral sclerosis. Nature. Published online April 3, 2020. doi: 10.1038/s41598-020-62756-8