Persistent Effect of Arimoclomol in Patients with Niemann-Pick Disease Type C: 24-Month Results from an Open-Label Extension of a Pivotal Phase 2/3 Study

Background/Purpose: Niemann-Pick disease type C (NPC), a rare, progressive neurodegenerative disease, has considerable unmet need. The 12-month, double-blind (DB), placebo-controlled, Phase 2/3 NPC-002 study suggested a clinically meaningful effect of arimoclomol on NPC progression. We present interim results of a 24-month open-label extension (OLE), providing efficacy and safety data for arimoclomol up to Month 36 (M36).

Methods: All OLE patients received arimoclomol; routine clinical care, including miglustat, was maintained. The primary endpoint was change in disease severity based on 5-domain NPC Clinical Severity Scale (5D-NPCCSS) scores from baseline to months 18, 24, 30, and 36. Subgroups comprised participants aged ≥4 years, treated with miglustat and without double functional null mutations.

Results: Forty-one participants entered the OLE (arimoclomol, n = 26; placebo, n = 15); 33 completed at month 36. At month 36, sustained benefit of arimoclomol was observed on the 5D-NPCCSS, with a mean (SD) change from baseline of 3.5 (5.6) for the arimoclomol-arimoclomol group (3 years’ arimoclomol treatment; DB and OLE) and 0.9 (2.1) for the placebo-arimoclomol group (2 years’ arimoclomol treatment; OLE only). In comparison, NPC progression (SE) with only standard of care was 5.2 (1.41) after 3 years and 3.5 (0.94) after 2 years, as estimated by extrapolation from NPC-001 observational and NPC-002 placebo data. A consistent benefit of sustained arimoclomol treatment was observed across subgroups at M36. The proportion of adverse events at M12–24 (87.8%) and M24–36 (82.9%) were similar to the DB phase (88.2%).

Conclusion: Arimoclomol provided sustained treatment effect over 36 months; it was well tolerated, with a consistent safety profile.