FDA Greenlights First Treatment for Niemann-Pick Disease Type C

The Food and Drug Administration (FDA) has approved Miplyffa (arimoclomol; Zevra Therapeutics, Celebration, FL) for use in combination with miglustat for the treatment of neurologic manifestations of Niemann-Pick disease type C (NPC) for adult and pediatric patients aged ≥2 years. Miplyffa is a capsule that is administered orally 3 times daily, and it is the first FDA-approved medication for NPC. In conjunction with the approval, Zevra Therapeutics announced that it has received a rare pediatric disease priority review voucher, enabling the company to receive a priority review for an additional product.

The FDA approval is based on the totality of data from Miplyffa’s New Drug Application, including positive data from a randomized, double-blind, placebo-controlled trial with a population of 50 participants with NPC who were aged 2 to 19 years. Participants were randomly assigned 2:1 to receive either Miplyffa at a weight-assigned dose or placebo 3 times daily. Thirty-nine (78%) participants received miglustat as a background treatment during the 12-month trial, and in these individuals, efficacy of Miplyffa was measured according to restored 4-domain NPC Clinical Severity Scale (R4DNPCCSS).

• The 76% of participants in the treatment group who received Miplyffa in combination with miglustat experienced a 0.2-point decrease in R4DNPCCSS score from baseline through 12 months.
• The 81% of participants in the placebo group who received miglustat alone experienced a 1.9-point decrease in R4DNPCCSS score from baseline through 12 months.

The trial results demonstrate that, compared with placebo, Miplyffa is associated with the halting of disease progression. Additionally, confirmatory evidence, such as data from a 48-month open label extension (OLE) study, suggest that people who receive Miplyffa experience improved disease outcomes compared with a natural history cohort. The most common adverse reactions associated with treatment are upper respiratory tract infection, diarrhea, and decreased weight. Miplyffa’s prescribing information includes precautions for hypersensitivity reactions, embryofetal toxicity, and increased creatinine without affecting glomecular function.

NPC is a rare lysosomal storage disease with a range of clinical manifestations, often presenting in children aged <10 years. The condition is associated with progressive neurologic disease, with symptoms including developmental delays, cognitive decline, tremor, epilepsy, and cerebellar ataxia, among others, with a terminal stage characterized by severe dementia, weakness, and loss of volitional movement. Miplyffa functions by increasing activation of transcription factor EB (TFEB) and transcription factor E3 (TFE3), upregulating the coordinated lysosomal expression and regulation (CLEAR) genes.