ATX-MS-1467 is a potential disease-modifying therapy for relapsing-remitting multiple sclerosis (RRMS). Its developer, Apitope, reports that the peptide-based therapeutic agent could benefit up to 70 percent of people with MS who have a specific genetic profile.
How ATX-MS-1467 works
In patients with MS, the myelin sheath (a fatty layer that protects and insulates nerve fibers) is damaged by the immune system attacking it. As a result, there is interference in the signals passed around the body and eventual permanent nerve damage leading to the symptoms of MS.
The immune system works by identifying certain molecules called “antigens” as foreign, and producing immune cells (such as T-cells) to attack and destroy the cell that has that antigen. In MS, the body mistakenly recognizes the myelin protein to be a foreign antigen.
ATX-MS-1467 consists of four short peptides derived from the basic protein of myelin, which is a key autoantigen (a trigger for an auto-immune response) in MS. ATX-MS-1467 aims to induce an immunological tolerance in T-cells to key auto-antigens involved in the clinical development of MS. In other words, it seeks to reduce MS attacks by desensitizing (switching off) the autoimmune response to myelin. Gradually increased doses of ATX-MS-1467 could make the immune system adjust to their presence and prevent immune attacks against myelin.
ATX-MS-1467 in clinical trials
Preliminary results from a small-scale Phase 1 clinical trial in six patients with secondary progressive multiple sclerosis (SPMS) were promising, and are published in the scientific journal Neurology, Neuroimmunology & Neuroinflammation.
Following this, a second Phase 1 study was successfully completed (NCT01097668). This second study assessed the safety and biological parameters of ATX-MS-1467 in 43 RRMS patients. The primary goal was safety and tolerability, determined through adverse effects and magnetic resonance imaging (MRI) scans. A secondary goal was identifying early signs of effectiveness. MRI scans showed a significant decrease in new lesions, which is an early indicator of potential effectiveness.
An open-label Phase 2a study (NCT01973491) evaluated the effects of ATX-MS-1467 in 19 people with relapsing MS. ATX-MS-1467 was administered under the skin every two weeks for 20 weeks. Following an initial dosing of 50 to 200 microgram (mcg) in the initial four weeks of treatment, a dose of 800 mcg was administered every two weeks for another 16 weeks. Trial results, released in February 2017, reported statistically significant reductions in the number of brain lesions measured by MRI during treatment, as well as a significant reduction in lesion volume. The data also showed a strong tendency toward improvement in the Multiple Sclerosis Functional Composite (MSFC) score, a clinical indicator of changes in disability. There were no treatment-related serious adverse events and the drug’s side effects profile was mild.
Apitope is now preparing for a placebo-controlled Phase 2b trial to assess the clinical efficacy of ATX-MS-1467.