Levacetylleucine Receives FDA Approval as Stand-Alone Therapy for Niemann-Pick Disease Type C
The approval marks the only FDA-approved stand-alone therapy for the treatment of Niemann-Pick disease type C (NPC).
The FDA and IntraBio have announced the US regulatory approval of levacetylleucine (Aqneursa; IntraBio) for the treatment of neurological manifestations of Niemann-Pick disease type c (NPC) in adults and pediatric patients that weigh at least 15 kg.1
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Approval of levacetylleucine was based on the randomized, double-blind, placebo-controlled IB1001-301 clinical trial (NCT05163288). The trial evaluated the impact of the therapy on neurological functioning in a cohort of 60 patients, meeting the primary efficacy end point of significantly improved neurological symptoms within 12 weeks.2
“Patients and families in the NPC community have long awaited an effective, FDA-approved treatment, and we are proud to bring hope to those affected by this devastating disease,” Mallory Factor, president and CEO of IntraBio, said in a news release.1
This approval follows the recent clearance of arimoclomol (Miplyffa; Zevra Therapeutics), an oral therapy for the treatment of patients with NPC. FDA approved arimoclomal in combination with miglustat, an enzyme inhibitor. Though this combination was the first FDA-approved NPC treatment, yesterday’s announcement marks the first approval of a stand-alone therapy for NPC.3
FDA investigators assessed the primary outcome using the Scale for the Assessment and Rating of Ataxia, referred to as the functional SARA (fSARA), which assesses factors such as gait, stability, and speech.1
Results from the trial indicated that patients who received levacetylleucine compared with placebo demonstrated a greater improvement in fSARA score. After 12 weeks of receiving levacetylleucine, the mean change from baseline SARA score was -1.97±2.43; for those treated with placebo, the difference was -0.60±2.39 points.4
Investigators determined a mean treatment difference of -0.4 (95% CI: -0.7, -0.2), with a 2-sided p-value of < .001. These results were supported by consistent results that the original SARA indicated.1,4
Critically, levacetylleucine was observed to be well-tolerated in patients throughout the trial. The most common adverse reactions, according to IntraBio, were abdominal pain, upper respiratory tract infections, vomiting, and dysphagia. There were no adverse events (AEs) that led to the premature discontinuation of the trial; though 3 patients each had 1 AE that the investigator assessed to be related to levacetylleucine.4
Some limitations of the trial were reported by the original investigators. They noted that the 12-week duration of the study limited their ability to provide insight into the effect of levacetylleucine on disease progression and AE incidence. Furthermore, some groups of patients were excluded due to the focus on symptomatic end points.4
However, these results confirmed the significant efficacy of levacetylleucine for patients with this rare condition, leading to its regulatory approval. According to Factor, clinical research indicates that levacetylleucine could potentially treat other types of neurodevelopmental and neurodegenerative disorders.1,4
“We will continue to rapidly develop Aqneursa [levacetylleucine] for these additional indications,” Factor said.1
