Arimoclomol Becomes First FDA Approved Treatment for Neimann-Pick Disease Type C

Arimoclomol (Miplyffa; Zevra Therapeutics), an oral medication, was approved by the FDA today for the treatment of Niemann-Pick disease, type C (NPC), according to a news release from the agency.¹

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In combination with miglustat, an enzyme inhibitor, arimoclomol is approved to treat the neurological symptoms associated with NPC in adults and children aged 2 years or older. This is the first FDA-approved treatment for NPC, a rare genetic disease that can cause organ dysfunction.¹

“NPC is a serious disease that leads to enormous adverse impacts on patients and families. Despite extensive research efforts, there have not been approved treatments to meet the significant needs of patients,” Janet Maynard, MD, MHS, director in the FDA’s Center for Drug Evaluation and Research, said in a news release. “The first-ever approval of a safe and effective drug option for NPC will undoubtedly support the essential medical needs of those suffering.”¹

Individuals that are affected by NPC, on average, live for about 13 years following diagnosis. The disease is caused by variations in either the NPC1 or NPC2 gene; these changes affect the required transportation of cholesterol and other types of lipids inside a cell. When these changes occur, cells don’t function normally, ultimately causing organ damage throughout the body.¹

NPC is a type of lipid storage disease, which are a group of inherited metabolic disorders where harmful levels of lipids build up in cells and tissues throughout the body. In patients with NPC, they are unable to properly break down cholesterol and other lipids.²

The effectiveness of arimoclomol was examined in a randomized, double-blind, placebo-controlled, 12-month trial. Enrolled patients were aged 2 to 19 years and had a molecularly confirmed diagnosis of NPC. In total, 50 patients were randomized to receive either weight-adjusted arimoclomol or placebo orally 3 times per day. Additionally, 39 patients among these 50 received background treatment of miglustat.¹

Investigators evaluated the efficacy of the treatment using the rescored 4-domain NPC Clinical Severity score (R4DNPCCSS) in the patients utilizing miglustat background therapy. This score is a measure of disease progression that analyzes 4 factors that patients with NPC, their physicians, and their caregivers have deemed most important: ambulation, speech, fine motor skills, and swallowing.¹

A higher score given to a patient represented more severe disease. Critically, when compared with placebo, arimoclomol demonstrated slower disease progression in patients with NPC as measured by the R4DNPCCSS score, according to the news release. Furthermore, over the course of 2 years, adults in the study generally had stable disease control.^1,3

The long-term positive results, from the arimoclomol expanded access program (NCT04316637), were announced at the Society for Inherited Metabolic Disorders 45th Annual Meeting in April 2024.⁴

Important prescribing information is listed for arimoclomol. Most importantly, the drug contains a warning for hypersensitivity reactions to patients, including hives and swelling under the skin. Other common side effects of arimoclomol include diarrhea, decreased weight, and upper respiratory tract infection.¹

Arimoclomol’s effectiveness and product application was the first to be discussed at the inaugural meeting of the Genetic Metabolic Diseases Advisory Committee in August 2024.¹

REFERENCES

1. FDA. FDA approves first treatment for Niemann-Pick disease, type C. News Release. Released September 20, 2024. Accessed September 20, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-niemann-pick-disease-type-c?utm_medium=email&utm_source=govdelivery

2. National Institute of Neurological Disorders and Stroke. Lipid storage diseases. National Institute of Health. Last updated August 2, 2024. Accessed online September 20, 2024. https://www.ninds.nih.gov/health-information/disorders/lipid-storage-diseases

3. Zevra Therapeutics. Zevra Therapeutics presents new data on the long-term safety and efficacy of arimoclomol as a treatment for Niemann-Pick disease type C at the SMD 45th annual meeting. News Release. Released April 15, 2024. Accessed September 20, 2024. https://investors.zevra.com/news-releases/news-release-details/zevra-therapeutics-presents-new-data-long-term-safety-and

4. ClinicalTrials.gov. Early access program with arimoclomol in US patients with NPC. National Library of Medicine. Last updated August 16, 2024. Accessed September 20, 2024.