Real-World Outcomes of Arimoclomol in Patients With Niemann Pick Type C скачать в хорошем качестве

Real-World Outcomes of Arimoclomol in Patients With Niemann Pick Type C

Caroline Hastings, MD, Pediatric Hematology Oncology, Professor of Pediatrics at the University of California, San Francisco, discusses real-world outcomes of arimoclomol in patients with Niemann Pick type C (NPC). NPC is a complex lysosomal storage disorder mainly 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. Arimoclomol is a heat-shock protein co-inducer designed to increase the activation of the transcription factors EB (TFEB) and E3 (TFE3) resulting in the upregulation of Coordinated Lysosomal Expression And Regulation (CLEAR) genes. The treatment has also been shown to reduce unesterified cholesterol in the lysosomes of human NPC fibroblasts. Arimoclomol was approved by the US Food and Drug Administration (FDA) for the treatment of NPC in September 2024. An early access program (EAP) was launched in the US to provide arimoclomol to patients with NPC who were not eligible for or able to participate in clinical trials or who stopped receiving treatment from the open-label extension study. A total of 14 sites enrolled 111 participants into the EAP, where 109 were treated with arimoclomol and consented to real-world data collection. There were 71 participants who also received miglustat and 38 received arimoclomol only. At commercialization, 81 participants opted for commercially available arimoclomol. Reasons for discontinuation were death not related to treatment with arimoclomol in 11.0% of participants, adverse events in 4.6% of participants, withdrawal of consent in 2.8% and treatment initiation with another investigational treatment for NPC in 1.8% of participants. A total of 248 adverse events were reported, with 241 being treatment-emergent. 36 participants experienced 95 serious adverse events, however, none were related to treatment. 12.8% of participants experienced 17 adverse events related to arimoclomol; 9 of which were resolved, 3 resolving, 4 not resolving, and 1 unknown. A total of five participants withdrew due to adverse events. No new safety signals were identified. In terms of efficacy, data demonstrated stability of the 5DNPCCSS and R4DNPCCSS, reinforcing the impact of arimoclomol treatment as mean annual disease progression in natural history studies increased 1.5 points on the 5DNPCCSS in pediatric patients; annual disease progression in the EAP remained below the 1-point or greater threshold that defines a clinically meaningful increase in disability and loss of complex function. Chapters: Introduction 00:00 NPC Overview 00:35 Current Management 2:14 Real-World Outcomes of Arimoclomol 3:59 Take Home Message 6:32