With a prevalence of 1 in 200,000 in Europe, inclusion body myositis is the most common idiopathic myositis after the age of 50. It is characterized by an often asymmetric muscle involvement with amyotrophy and begins in the quadriceps and / or flexors of the fingers. Muscle biopsy shows two phenomena: inflammation and degeneration with accumulation of different proteins (beta-amyloid, phosphorylated tau, etc.). The pathophysiology of inclusion body myositis could involve an underexpression of heat-shock proteins (HSPs) which have the capacity to destroy protein aggregates, repair proteins with abnormal folding and improve the functioning of lysosomes.
Lack of efficacy, even at high doses
Developed by the Danish laboratory Orphazyme, arimoclomol enhances the production of heat shock proteins. It had obtained encouraging results in inclusion body myositis in preclinical studies, but its efficacy was not confirmed in a small clinical trial (24 participants) which evaluated it at a dose of 300 mg / day. A four times higher daily dose was tested against placebo for 20 months in 150 participants in the United Kingdom and the United States, a new trial which Orphazyme announced the failure in a press release published at the end of March 2021. Its candidate drug did not meet either the primary endpoint (IBM-FRS functional score) or the secondary endpoints (manual muscle testing, 6 minutes walk test, maximum voluntary isometric quadriceps contraction, etc.). It will no longer be developed in inclusion body myositis but its path continues in amyotrophic lateral sclerosis and in two lysosomal pathologies: Gaucher disease and Niemann-Pick disease.
Orphazyme [online] Orphazyme announces topline results from pivotal trial of arimoclomol for Inclusion Body Myositis (IBM) – 2021/03/29 [accessed 2021/04/06].
