Arimoclomol in infants with Niemann-Pick disease type C: Results from the phase 2/3 open-label pediatric substudy

Background: Arimoclomol has been approved in the US for the treatment of Niemann-Pick disease type C (NPC) in patients aged ≥2 years, in combination with miglustat. This multicenter, open-label substudy of the phase 2/3 NPC-002 trial (NCT02612129) evaluated the safety, pharmacokinetics (PK) and impact on clinical status outcomes of arimoclomol in infants with NPC 6-<24 months of age. Methods: Infants with NPC aged 6-<24 months received arimoclomol in addition to their standard of care management for up to 36 months. The dosing regimen used for patients <24 months differed from the regimen recommended in the FDA label. The primary endpoint was safety and tolerability of arimoclomol; secondary endpoints were changes in clinical status (physical examination and Bayley III developmental scores), biomarkers, and PK. Results: Five patients (three females, two males; aged 14-23 months at screening) were enrolled; four remained in the study >12 months; arimoclomol exposure ranged from 72 to 1109 days. All patients received concomitant miglustat. Across 108 reported adverse events (AEs), most were considered mild or moderate in severity and non-serious. A total of 15 serious AEs were reported for two patients. Two AEs in one patient (elevated alanine/aspartate aminotransferases) were considered probably related to arimoclomol and resolved within 51 days; the patient was withdrawn from the substudy. No clinically significant changes were observed in hematology, kidney ultrasound imaging, or vital signs. Mean arimoclomol exposure over the first 8 h post-dose (1378.3-2988 h∙μg/L) was comparable to levels in NPC patients aged 2-19 years. Changes in Bayley III scores and biomarkers varied between individuals. Conclusion: Arimoclomol was well tolerated in infants initiating treatment before 2 years of age, with no new safety signals. PK profiles support the dosing regimen used. These findings suggest that early initiation of arimoclomol could be considered for the 6-24-month population. Further investigation in larger cohorts is warranted to elucidate the impact of arimoclomol in NPC patients under 2 years of age.