With a prevalence of 1 in 200,000 in Europe, sporadic inclusion myositis is the most common idiopathic myositis after the age of 50. It is characterised by muscle damage, often asymmetric with amyotrophy, and begins in the quadriceps and/or finger flexors. Muscle biopsy shows two phenomena: inflammation and degeneration with accumulation of various proteins (beta-amyloid, phosphorylated tau, etc.). The pathophysiology of inclusion myositis may involve under-expression of heat-shock proteins (HSPs), which are capable of destroying protein aggregates, repairing abnormally folded proteins and improving the functioning of lysosomes.
Lack of efficacy, even at high doses
Initially developed by the Danish laboratory Orphazyme, arimoclomol amplifies the production of heat shock proteins. It had produced encouraging results in preclinical studies of inclusion myositis, but its efficacy was not confirmed in a small clinical trial (24 participants) which evaluated it at a dose of 300 mg per day. A daily dose four times higher was tested against placebo for 20 months in 150 participants in the United Kingdom and the United States, a new trial which Orphazyme announced had failed in a press release published at the end of March 2021.
The final results were published in October 2023 in The Lancet: arimoclomol did not meet either the primary endpoint (IBMFRS functional score) or the secondary endpoints (manual muscle testing, 6-minute walk, maximum voluntary isometric contraction of the quadriceps, etc.). Nevertheless, the scale of this trial, which was unprecedented in the field of inclusion myositis, enabled the acquisition of data on the course of the disease which will be useful for the design of future trials, particularly with regard to the choice of evaluation criteria and the relevance of setting up sub-groups of participants who are symptomatically homogeneous.
Orphazyme [online] Orphazyme announces topline results from pivotal trial of arimoclomol for Inclusion Body Myositis (IBM) – 29 March 2021 press release [consulted on 6 April 2021]
