First drug approved against Niemann-Pick disease type C

The FDA on Friday approved arimoclomol (Miplyffa) as the first treatment specifically for the genetic disorder Niemann-Pick disease type C (NPC), an extremely rare and progressive neurodegenerative disease.

Arimoclomol oral capsules are indicated in combination with miglustat, an enzyme inhibitor, for the treatment of neurological manifestations of NPC in adults and children aged 2 years and older.

Approval was based on limited data from a small Phase II/III study in which arimoclomol was associated with slower disease progression on the reassessed 4-domain clinical severity scale for NPC (R4DNPCCSS), with the primary endpoint including the domains of walking, fine motor skills, speaking and swallowing. Study participants had a molecularly confirmed diagnosis of NPC and 78% were receiving background treatment with miglustat.

Over the course of one year of treatment, arimoclomol in combination with miglustat stopped disease progression as measured by R4DNPCCSS, resulting in a 0.2 point reduction from baseline, while miglustat alone resulted in an increase of 1.9 points, drugmaker Zevra Therapeutics said in its press release announcing the approval.

Arimoclomol, in particular, was rejected by the FDA in 2021 but received the support of an advisory committee last August, whose members voted for approval because the need in NPC is great and the evidence is “slightly positive” or “weak.” It is estimated that there are 900 people living with this rare disease in the United States.

NPC is caused by mutations in the NPC1 or NPC2 genes. It is characterized by a person's inability to transport lipids within cells. The abnormal accumulation of lipids damages organs and is often fatal.

“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, director of FDA's Office of Rare Diseases, Pediatrics, Urology and Reproductive Medicine, in a statement. “The first-ever approval of a safe and effective drug option for NPC will undoubtedly meet the essential medical needs of those affected.”

The mechanism of action of arimoclomol is unknown.

The drug's label does not list any contraindications, but warns of hypersensitivity reactions, possible harm to the fetus, and a significant increase in serum creatinine by 10-20%. The most common side effects in studies were upper respiratory tract infections, diarrhea, and weight loss, with rates of 15% or more.

Arimoclomol is administered orally three times daily with or without food, with the dosage (47 mg to 124 mg) depending on the patient's body weight.

Zevra expects the drug to be available within 8 to 12 weeks.