NPC1

Within the span of a week, the FDA gave the green light to another drug for the rare condition Niemann-Pick disease type C in the form of IntraBio’s levacetylleucine. On Friday, the FDA approved Zevra Therapeutics’ Miplyffa for NPC when added to Johnson & Johnson’s enzyme inhibitor Zavesca. Zevra had resubmitted the thrice-daily pill with a reanalysis of its registrational trial after its initial attempt at approval was rejected in 2021. The approval of IntraBio’s levacetylleucine, which will be marketed as Aqneursa, was based on data from a 60-participant Phase 3 trial that showed the treatment achieved a “clinically meaningful” 1.37-point reduction on the Scale for the Assessment and Rating of Ataxia (SARA) score at 12 weeks versus placebo (p<0.001). SARA measures a patient’s level of muscle control when doing activities like walking, sitting and standing in place. Aqneursa, which is a modified amino acid drug, is indicated for both adults and children weighing at least 15 kg. The oral treatment can be taken up to three times per day with dosing dependent on patient weight. The back-to-back authorizations reflect the FDA’s “commitment to support development of new treatments for rare diseases,” Janet Maynard, director of CDER’s Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, said in a Tuesday release. Prior to these approvals, the only options to manage NPC were pain medications, physical therapy and speech therapy, among other strategies. Zavesca, which is approved for certain patients with Gaucher disease in the US, is also an off-label option. Driven by changes in the NPC1 or NPC2 genes, NPC causes poor muscle tone, difficulty coordinating movements and progressive organ damage. There are around 300 to 350 people with the condition in the US, according to William Blair analysts.

iStock, hapabapa IntraBio’s Aqneursa is the second drug within a week approved by the regulator for treating Niemann-Pick disease type C, just days behind Zevra Therapeutics’ Miplyffa. The FDA on Tuesday signed off on IntraBio’s levacetylleucine for the treatment of Niemann-Pick disease type C. The drug, which will now be marketed under the brand name Aqneursa, is indicated to ease neurological symptoms in both adults and children weighing at least 15 kg. Aqneursa was backed by data from a randomized, double-blinded and placebo-controlled crossover study. During the 12-week period that patients were treated with Aqneursa, they showed better functional performance as measured by a score that assesses their gait, sitting, stance and speech. The study also found Aqneursa to be well-tolerated, with common side effects being vomiting, abdominal pain, difficulty swallowing and upper respiratory tract infections. The drug’s label includes a warning for embryo-fetal harm if used during pregnancy, according to the FDA’s announcement. It remains unclear how much Aqneursa will cost or when it will launch. Afflicting approximately one in every 150,000 people , Niemann-Pick disease type C (NPC) is an ultra-rare and neurodegenerative lysosomal storage disease that involves the progressive impairment of patients’ physical and cognitive function. Mutations in the NPC1 and NPC2 genes compromise the body’s otherwise healthy mechanism of clearing cholesterol and other lipids from inside cells, leading to their pathologic build-up in the brain and in other crucial organs. NPC affects patients’ speech, motor and swallowing functions. According to the FDA, patients with NPC typically live only up to around 13 years. Aqneursa’s approval on Tuesday marks the second NPC approval in a week, highlighting the regulator’s “commitment” to supporting the development of innovative therapies for rare diseases, Janet Maynard, director of the FDA’s Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, said in a statement. OnFriday, the regulator greenlit Zevra Therapeutics’ oral drug Miplyffa (arimoclomol), also for the treatment of the neurological manifestations of NPC. Miplyffa is meant to be taken with miglustat and can be administered to adults and children aged two years and older. Like Aqneursa, Miplyffa can be given up to three times per day, with or without food, with the exact dosing schedule depending on the patients’ body weight. Zevra in a conference call on Monday announced that it would price Miplyffa between $40,000 to $106,000 per month, depending on dosage, according to Reuters . The company expects to launch Miplyffa in eight to 12 weeks.

The FDA has approved IntraBio’s Aqneursa (levacetylleucine), for the treatment of neurological symptoms associated with Niemann-Pick disease type C (NPC). NPC is caused by mutations in the NPC1 or NPC2 genes, disrupting cholesterol and lipid transport within cells and leading to organ damage. Most individuals with the disease have a significantly reduced life expectancy, often surviving only about 13 years. The approval marks the second NPC treatment approved by the FDA in a week. Aqneursa’s effectiveness was demonstrated in a 24-week, randomized, double-blind, placebo-controlled study involving 60 patients with confirmed NPC diagnoses. The study used a modified version of the Scale for the Assessment and Rating of Ataxia (SARA) to measure neurological function. Patients treated with Aqneursa for 12 weeks showed significant improvements in their functional SARA scores compared to those on placebo. The drug works by modulating intracellular pathways that are involved in lipid metabolism. Although the precise mechanism of action for treating NPC remains unclear, it is thought to help stabilize neuronal function and improve the transport of cholesterol and other lipids within cells. This transport is disrupted in NPC, leading to lipid accumulation and cell damage. By addressing these imbalances, Aqneursa may help reduce the neurological symptoms associated with the disease, such as motor dysfunction and cognitive decline. Earlier this week, the FDA approved Zevra Therapeutics’ Miplyffa (arimoclomol) for the treatment of NPC. Miplyffa, used in combination withmiglustat, is the first FDA-approved therapy and was cleared after demonstrating modest clinical benefits and a favorable safety profile.