Elezanumab did not outperform placebo in progressive and relapsing MS

Elezanumab did not improve physical function or disability in patients with relapsing or progressive MS. The drug showed favourable safety and tolerability profiles and is currently investigated in other neurological conditions [1].

Elezanumab is a fully humanised, monoclonal antibody, selectively binding to repulsive guidance molecule A (RGMa). This molecule is an inhibitor of axon regeneration, neurite outgrowth, and remyelination in the CNS. Antibody neutralisation of RGMa has been linked to enhanced neuronal regeneration and increased neuroprotection in animal models [2]. RADIUS-R (NCT03737851; n=208) and RADIUS-P (NCT03737812; n=123), 2 randomised, double-blind, placebo-controlled, phase 2 trials investigated the efficacy and safety of elezanumab as add-on treatment in patients with relapsing MS and progressive forms of MS, respectively. In both trials, patients were randomised 1:1:1 to elezanumab 1,800 mg (intravenous, every 4 weeks), elezanumab 400 mg, or placebo, in addition to standard-of-care disease-modifying therapy. The most common co-treatment was ocrelizumab, which was used by >50% of the patients in each trial. The primary endpoint was the mean Overall Response Score (ORS) at week 52. Prof. Bruce Cree (University of California, CA, USA) presented the results.

Elezanumab 1,800 mg or 400 mg did not improve the ORS at week 52 compared with placebo in patients with relapsing MS or progressive MS. In addition, the key exploratory endpoints –Symbol Digit Modalities Test (SDMT), Low Contrast Visual Acuity (LC-VA), Modified Fatigue Impact Scale (MFIS), and brain and cervical spinal cord MRI– did not demonstrate clinically significant changes following elezanumab therapy. Similarly, other biomarkers, such as daily step count, neurofilament light, or glial fibrillary acidic protein did not display benefits of elezanumab over placebo in these populations. Elezanumab was generally safe and well tolerated and the patient retention was excellent, with 88% of the patients completing treatment with the study drug in each trial. There was no imbalance in treatment emergent adverse events (AEs) across the arms of the trials. The most common AEs were urinary tract infections, falls, infusion-related reactions, fatigue, headache, arthralgia, and muscular weakness.

1. Cree BAC, et al. Safety and Efficacy of Elezanumab in Relapsing and Progressive Forms of Multiple Sclerosis: Results From Two Phase 2 Studies, RADIUS-R and RADIUS-P. OP149, ECTRIMS 2021 Virtual Congress, 13–15 October.
2. Demicheva E, et al. Cell Rep. 2015;10:1887–1898.

 

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Posted on 9 December 20219 December 2021