FDA Approves Levacetylleucine for Niemann-Pick Disease Type C

Credit: US Food and Drug Administration

The US Food and Drug Administration (FDA) has approved IntraBio’s levacetylleucine (Aqneursa) for the treatment of neurological symptoms associated with Niemann-Pick disease type C (NPC) in adults and pediatric patients weighing ≥15 kg.¹

Announced on September 24, 2024, the treatment marked the second approval for NPC for the agency in a week, following approval of Zevra Therapeutics’ arimoclomol (Miplyffa).² In their announcement, IntraBio indicated levacetylleucine is the only FDA-approved stand-alone therapy for the treatment of NPC.¹

“The FDA approval of [levacetylleucine] marks a significant breakthrough for those living with NPC,” said Laurie Turner, family services manager at the National Niemann-Pick Disease Foundation.¹ “For too long, our community has been without an approved therapy for the treatment of NPC. Today we celebrate this tremendous milestone for individuals and families living with NPC.”

A rare, inherited disease, NPC occurs in approximately 1 in 100,000 live births. The disease results in progressive neurological symptoms and organ dysfunction, severely impacting functional abilities and reducing quality of life.³ Treatment approaches have traditionally been unable to address the devastating effects of NPC on a patient’s daily life.

Approval of levacetylleucine was awarded based on results from the multinational, randomized, double-blind, placebo-controlled, pivotal IB1001-301 clinical trial.¹ The trial evaluated the effect of levacetylleucine on neurological symptoms and functioning in pediatric (≥4 years) and adult patients (n = 60), with a confirmed diagnosis of NPC.

According to results published in the New England Journal of Medicine, IB1001-301 met its primary efficacy and all secondary endpoints in patients treated with levacetylleucine. Levacetylleucine significantly improved neurological signs and symptoms, with functional benefits important to daily life achieved within 12 weeks.

The primary outcome assessed by the FDA was a functional version of the Scale for the Assessment and Rating of Ataxia (fSARA), evaluating the original scale's gait, sitting, stance, and speech disturbance domains with scoring modifcations. Patients who received levacetylleucine achieved a greater improvement in fSARA score, with a mean treatment difference of –0.4 (95% CI, –0.7 to –0.2; two-sided P-value <.001) versus placebo.

According to safety data in IB1001-301, levacetylleucine remained tolerable, with the most common adverse reactions (incidence ≥5%) being abdominal pain, dysphagia, upper respiratory tract infections, and vomiting.

Prescribing information indicated levacetylleucine should be taken orally up to three times per day, with or without food, with recommended doses varying depending on the individual's body weight.⁴ The FDA previously granted Aqneursa Priority Review, Fast Track, Orphan Drug and Rare Pediatric Disease designations to levacetylleucine for this application.

“Today's action further underscores the agency's commitment to support development of new treatments for rare diseases," said Janet Maynard, MD, director of the Office of Rare Diseases, Pediatrics, Urologic, and Reproductive Medicine, in the FDA's Center for Drug Evaluation and Research.⁴ "This approval again demonstrates the FDA's commitment to work with the scientific community to overcome the unique challenges that may arise with rare disease drug development."

References

1. _{Intrabio announces U.S. FDA approval of Aqneursa for the treatment of Niemann-Pick Disease Type C. IntraBio. September 25, 2024. Accessed September 25, 2024. https://intrabio.com/news/intrabio-announces-u-s-fda-approval-of-aqneursa-for-the-treatment-of-niemann-pick-disease-type-c/.}
2. _{Iapoce C. FDA approves Arimoclomol, first drug for Niemann-Pick disease, type C. HCP Live. September 20, 2024. Accessed September 25, 2024. https://www.hcplive.com/view/fda-approves-arimoclomol-first-drug-for-niemann-pick-disease-type-c.}
3. _{Bianconi SE, Hammond DI, Farhat NY, et al. Evaluation of age of death in Niemann-Pick disease, type C: Utility of disease support group websites to understand natural history. Mol Genet Metab. 2019;126(4):466-469. doi:10.1016/j.ymgme.2019.02.004}
4. _{Commissioner O of the. FDA approves new drug to treat Niemann-Pick disease, type C. U.S. Food and Drug Administration. September 24, 2024. Accessed September 25, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treat-niemann-pick-disease-type-c.}