Arimoclomol Demonstrates Sustained Effect in Niemann-Pick Disease Type C

Arimoclomol is a small molecule designed to amplify and sustain the cellular production of heat shock proteins, particularly HSP70, which targets protein misfolding and improves lysosomal function.

The following article features coverage from the 17th Annual WORLDSymposium meeting. Click here to read more of MPR’s conference coverage.

Arimoclomol provided a sustained clinically meaningful treatment effect over 24 months in patients with Niemann-Pick disease type C, according to results from an extension study presented at the 17th Annual WORLDSymposium.

Arimoclomol is an investigational oral drug candidate that is designed to amplify and sustain the cellular production of heat shock proteins (HSPs). HSPs can rescue defective misfolded proteins, clear protein aggregates, and improve the function of lysosomes.

Findings from a 12-month double-blind (DB), placebo-controlled phase 2/3 study showed a clinically meaningful treatment effect on Niemann-Pick disease type C (NPC) progression with arimoclomol, as well as a tolerable safety profile. To assess its sustained efficacy and safety over 24 months, researchers conducted a 12-month, single-arm, open-label extension (OLE) study in 41 patients (arimoclomol, n=26; placebo, n=15) with NPC.

The OLE phase included patients 4 years of age or older maintained on miglustat and without double functional null mutations. The primary end point was change in disease severity based on 5-domain NPC Clinical Severity Scale (NPCCSS) scores from baseline to month 12 and to month 24 (12 months DB and 12 months OLE).

At 24 months, 34 patients completed the extension phase. Arimoclomol was found to demonstrate sustained benefit on the 5-domain NPCCSS at month 24, with a mean (SD) change from baseline of 2.4 (4.3). A clinically meaningful mean treatment benefit of 1.1 was maintained compared with an estimated natural progression of 3.46 (1.73 per year).

Additionally, a reduction in disease progression on 5-domain NPCCSS was observed when switching to arimoclomol from placebo, resembling disease stabilization. Additional clinical benefits were sustained with arimoclomol at 24 months, including decreased serum cholestane-triol levels, reduced unesterified cholesterol accumulation, and increased HSP70 levels from baseline.

The safety profile of arimoclomol in the extension phase was found to be consistent with results from the double blind study. A similar proportion of treatment-emergent adverse events (TEAEs) occurred at months 0-12 (88.2%) vs months 12-24 (92.3%), with a serious adverse event rate of 14.7% vs 30.8%, respectively.

Based on these results, the researchers concluded that arimoclomol demonstrated a sustained and clinically meaningful treatment effect over 24 months in Niemann-Pick disease type C, with an unchanged safety profile.

Disclosure: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Patterson MC, Mengel E, Da Riol RM, et al. Persistent effect of arimoclomol in patients with Niemann-Pick disease type C: 12-month results from an open-label extension of a pivotal phase 2/3 study. Presented at: 17th Annual WORLDSymposium; February 8-12, 2021. Poster# 191.