A recent paper published in Molecular Genetics and Metabolism presented safety and efficacy outcomes from the 48-month open-label extension of the NPC-002 study of arimoclomol in patients with Niemann-Pick type C (NPC).
NPC is a complex lipid storage disease caused by genetic changes in the NPC1 gene. It is characterized by the accumulation of unesterified cholesterol in the late endosomal/lysosomal compartment. Symptoms may include lack of muscle coordination, brain degeneration, learning problems, loss of muscle tone, increased sensitivity to touch, spasticity, feeding and swallowing difficulties, slurred speech, and an enlarged liver and spleen.
The NPC-002 clinical trial (NCT02612129) study was a phase 2/3, prospective, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of arimoclomol as an add-on therapy. Arimoclomol is an orally delivered heat-shock protein co-inducer. Its exact mechanism of action is unknown but evidence shows its ability to help clear lipid build-up in cells, improving lysosomal function.
A total of 41 patients entered the open-label extension and 29 completed the 48 months. During this period, mean 5-domain NPC Clinical Severity Scale (5DNPCCSS) and rescored 4-domain NPCCSS (R4DNPCCSS) scores increased by 3.2 and 2.7, respectively.
Among patients switching from placebo to arimoclomol after the double-blind phase, mean annual change in 5DNPCCSS decreased from 2 to 0.1 in the first year of receiving arimoclomol and mean annual change in R4DNPCCSS decreased from 1.9 to 0.2, indicating slowing of disease progression.
Annual scores for both endpoints remained numerically smaller throughout the open-label extension than during the double-blind phase. The score pattern in the subgroup of patients who received miglustat as part of standard care regimen in addition to arimoclomol was similar to that observed in the total population. 17-domain NPC Clinical Severity Scale and NPC clinical database score results further supported sustained efficacy of arimoclomol. Arimoclomol was also well-tolerated, with no new safety concerns identified.
To learn more about NPC and other rare lysosomal conditions, visit https://checkrare.com/diseases/lysosomal-storage-disorders/
