Two-year results from a phase 2 extension study of oral amiselimod in relapsing multiple sclerosis

Abstract

Background:Amiselimod, an oral selective sphingosine-1-phosphate 1 receptor modulator, suppressed disease activity dose-dependently without clinically relevant bradyarrhythmia in a 24-week phase 2, placebo-controlled study in relapsing-remitting multiple sclerosis.Objective:To assess safety and efficacy of amiselimod over 96 weeks.Methods:After completing the core study, patients on amiselimod continued at the same dose, whereas those on placebo were randomised 1:1:1 to amiselimod 0.1, 0.2 or 0.4 mg for another 72 weeks. Most patients receiving 0.1 mg were re-randomised to 0.2 or 0.4 mg upon availability of the core study results.Results:Of 415 patients randomised in the core study, 367 (88.4%) entered and 322 (77.6%) completed the extension. One or more adverse events were reported in 303 (82.6%) of 367 patients: ‘headache’, ‘lymphocyte count decreased’, ‘nasopharyngitis’ and ‘MS relapse’ were most common (14.7%–16.9%). No serious opportunistic infection, macular oedema or malignancy was reported and no bradyarrhythmia of clinical concern was observed by Holter or 12-lead electrocardiogram. The dose-dependent effect of amiselimod on clinical and magnetic resonance imaging-related outcomes from the core study was sustained in those continuing on amiselimod and similarly observed after switching to active drug.Conclusion:For up to 2 years of treatment, amiselimod was well tolerated and dose-dependently effective in controlling disease activity.

The S1P–S1PR Axis in Neurological Disorders—Insights into Current and Future Therapeutic Perspectives

“…In this regard, S1P 4 , as discussed previously in this review, is predominantly expressed in lymphoid tissues [88,95], and ligation and its subsequent signaling are involved in marking time regarding proliferation [286,287], a reduction of effector cytokines secreted [286,287], and migration of lymphocytes [288,289]. It is worth noting that amiselimod displays a very safe risk profile [290][291][292], while it is too early to consistently assess this for etrasimod [293]. Their application and/or investigation regarding their future therapeutic exploitability in neurological conditions should find due consideration soon.…”

Sphingosine 1-phosphate Receptor Modulator Therapy for Multiple Sclerosis: Differential Downstream Receptor Signalling and Clinical Profile Effects

“…Evaluation of ozanimod has involved a placebo-controlled and active-controlled (vs interferon beta-1a) combined RMS Phase 2/3 trial (RADIANCE) [12,138,139] and an active-controlled Phase 3 trial versus interferon beta-1a (SUNBEAM) in patients with RMS [11,140,141], while the assessment of ceralifimod in patients with RRMS has involved a placebo-controlled Phase 2 study (DreaMS) [142]. Ponesimod has been assessed in a placebocontrolled Phase 2b study (NCT01006265) [67], and a completed active-controlled Phase 3 trial versus teriflunomide (OPTIMUM) in patients with RRMS (NCT02425644), while the placebo-controlled Phase 2 MOMENTUM study and extension have evaluated amiselimod in patients with RRMS [143,144].…”

Efficacy and Safety of Etrasimod in a Phase 2 Randomized Trial of Patients With Ulcerative Colitis

“…[16][17][18][19][20] Other S1P receptor modulators are in clinical development as potential therapies, including ozanimod in multiple sclerosis and UC, [21][22][23] ponesimod in multiple sclerosis and psoriasis, 24,25 and amiselimod in multiple sclerosis and Crohn's disease. [26][27][28] Fingolimod, a first-generation S1P receptor modulator, interacts nonselectively with S1P isoforms 1 through 5. 9,14 This lack of selectivity has been suggested to contribute to some of the adverse events (AEs) observed in patients treated with fingolimod, including pulmonary fibrosis and elevation of liver enzymes.…”