FDA approves arimoclomol as first drug to treat Neimann-Pick disease type C

The FDA has approved the first drug to treat Neimann-Pick disease type C (NPC) in adults and children ages 2 and older.¹

According to the federal agency, arimoclomol (Miplyffa; Zevra Therapeutics) in combination with the enzyme inhibitor miglustat has been approved to treat the rare disease, which leads to progressive neurological symptoms and organ dysfunction.¹

“NPC is a serious disease that has a tremendous negative impact on patients and families. Despite extensive research efforts, there are no approved treatments that address the significant needs of patients,” said Janet Maynard, MD, MHS, in an FDA press release.¹

Maynard is director of the Office of Rare Diseases, Pediatrics in the FDA's Center for Drug Evaluation and Research. “The first-ever approval of a safe and effective drug option for NPC will undoubtedly address the essential medical needs of those affected,” Maynard added.¹

NPC is caused by changes in the NPC1 or NPC2 gene that affect the “necessary transport of cholesterol and other lipids within a cell,” the FDA wrote, causing cells to not function properly, ultimately leading to organ damage. Those affected by NPC live about 13 years.¹

Approval was supported by the safety and efficacy of arimoclomol demonstrated in a randomized, double-blind, placebo-controlled 12-month study in patients aged 2 to 19 years with a molecularly confirmed diagnosis of NPC. Fifty patients were randomized 2:1 to receive weight-adjusted arimoclomol (31 to 124 mg) or placebo orally three times daily. Thirty-nine of the 50 patients in the study received miglustat as background treatment.¹

Efficacy was demonstrated using the reassessed 4-domain NPC Clinical Severity Scale (R4DNPCCSS) score in patients using miglustat as baseline treatment. R4DNPCCSS is a measure of disease progression in NPC and takes into account 4 items identified by patients with NPC, their caregivers and physicians as the most relevant. These include walking, speaking, swallowing and fine motor skills. A higher score indicates a more severe disease progression and arimoclomol resulted in a slower disease progression as measured by the R4DNPCCSS score compared to placebo.¹

On September 6, 2024, data on arimoclomol were presented in four poster sessions at the 2024 Annual Symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM).²

In Poster 21260, treatment was evaluated in an additional 12-month placebo-controlled trial (NCT02612129) using the original 5-domain Niemann-Pick Type C Clinical Severity Scale (5DNPCCSS) and the modified 4-domain Niemann-Pick Type C Clinical Severity Scale (4DNPCCSS). A statistically significant treatment effect was demonstrated, as was the pre-specified primary endpoint of 5DNPCCSS, which is a clinically meaningful reduction in disease progression with arimoclomol treatment compared with placebo.²

Poster 21271 presented data from the 12-month double-blind and 48-month open-label extension portion of the study, which assessed walking, speaking, swallowing, and fine motor skills using the 4DNPCCSS.²

“In patients who switched from placebo to arimoclomol at the start of the open-label extension phase, the average annual rate of disease progression decreased from an annual rate of change of 1.9 points during the double-blind phase to a rate of 0.3 during the first 12 months of treatment. It remained numerically lower for the remainder of the study and was comparable between the double-blind phase of the study and the open-label extension phase of the study,” Zevra Therapeutics explained in a poster session summary.²

The prescribing information for arimoclomol includes a warning about hypersensitivity reactions such as hives and angioedema. People who experience these side effects should stop taking arimoclomol. Women who are pregnant or planning to become pregnant should not take arimoclomol.¹

According to the FDA, the most common side effects are upper respiratory infections, diarrhea and weight loss.¹

References:

1. FDA approves first treatment for Niemann-Pick disease type C. FDA. Press release. September 20, 2024. Retrieved September 20, 2024. https://content.govdelivery.com/accounts/USFDA/bulletins/3b708bf

2. Zevra Therapeutics presented new data on arimoclomol and OLPRUVA® (sodium phenylbutyrate) at the Society For The Study Of Inborn Errors Of Metabolism (SSIEM) 2024 Annual Symposium. Zevra Therapeutics. Press release. September 6, 2024. Retrieved September 20, 2024.