The approval follows phase 3 data that showed significant improvements in neurological symptoms and functional benefit over 12 weeks in patients with Niemann-Pick disease type C.
Mallory Factor
(Credit: IntraBio)
According to a new company announcement, the FDA has approved IntraBio’s levacetylleucine, an agent that ameliorates lysosomal and metabolic dysfunction, as a stand-alone treatment of neurological manifestations in Niemann-Pick disease type C (NPC) among adults and pediatric patients weighing at least 15 kg.1,2 Marketed as Aqneursa, the treatment becomes the second FDA-approved therapy indicated for NPC following the recently authorized arimoclomol (Miplyffa; Zevra Therapeutics).
The approval was based on data from the phase 3 double-blind, placebo-controlled, crossover trial IB1001-301 trial (NCT05163288), which investigated levacetylleucine among 60 patients aged between 5 years and 67 years of age with NPC over 12 weeks. In the trial, levacetylleucine met its primary efficacy end point, measured by the functional version of the Scale for the Assessment and Rating of Ataxia (fSARA), and all secondary end points. Published in the New England Journal of Medicine, patients who received levacetylleucine showed a greater improvement in fSARA score with a mean treatment difference of -0.4 (95% CI, -0.7to -0.2; P <.001) compared with placebo.3
"IntraBio has been dedicated to bringing novel treatments to patients with extremely high unmet medical needs like NPC, and today we celebrate a major milestone in this tremendous effort,” Mallory Factor, president and chief executive officer at IntraBio, said in a statement.1 “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. We remain committed to ensuring that all patients who can benefit from this novel treatment will have the opportunity to do so. Based on our clinical research, we believe that Aqneursa may hold potential for treating other rare and common neurodegenerative and neurodevelopmental disorders, and we will continue to rapidly develop Aqneursa for these additional indications.”
Conducted by lead author Tatiana Bremova-Ertl, MD, PhD, head of the neurometabolic outpatient clinic at Insel Gruppe, and colleagues, patients 4 years of age or older with NPC were randomly assigned in a 1:1 ratio to levacetylleucine for 12 weeks followed by placebo for 12 weeks or placebo for 12 weeks followed by levacetylleucine for 12 weeks. The participants were administered the agent or matching placebo orally 2 to 3 times per day: those who were 4 to 12 years of age received weight-based doses (2 to 4 g per day) and patients 13 years of age or older received a dose of 4 g per day. The primary end point of the study was the total score on the fSARA and the secondary end points included scores on the Clinical Global Impression of Improvement (CGI-I), the Spinocerebellar Ataxia Functional Index (SCAFI), and the Modified Disability Rating Scale (mDRS). In addition, crossover data from 2 of the 12-week periods in each group were included in the comparisons of levacetylleucine with the placebo.
“The FDA approval of Aqneursa marks a significant breakthrough for those living with Niemann-Pick disease type C," Laurie Turner, the family services manager at the National Niemann-Pick Disease Foundation, said in a statement.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. We are immensely thankful for the dedication to innovative research that has led to this approval, and we are ready to help families embark on this new chapter of treatment.”
In addition to positive results on the primary outcome, investigators observed mean differences of −0.6 points (95% CI, −1.1 to −0.1) in the changes of scores for the investigator-rated CGI-I; −0.7 points (95% CI, −1.2 to −0.2) for the caregiver-rated CGI-I; −0.5 points (95% CI, −1.1 to 0.1) for the patient-rated CGI-I. Additionally, authors noted mean differences of −0.029 points (95% CI, −0.048 to −0.010) in the changes in scores for the mDRS (mean baseline scores before receipt of the first dose of levacetylleucine, 0.477 [±0.124]; before receipt of the first dose of placebo, 0.475 [±0.142]); and 0.07 (95% CI, −0.0 to 0.15) for the SCAFI (mean baseline scores before receipt of the first dose of levacetylleucine, −0.39 [±1.04]; before receipt of the first dose of placebo, 0.35 [±1.02]).
In total, 79 adverse events (AEs) occurred for those on levacetylleucine (patients, n = 36), and 75 events occurred with placebo (patients, n = 30). Only 3 patients had 1 transient AE each related to levacetylleucine as assessed by the investigator. These included anal incontinence, restless legs, and rosacea. Investigators reported a 5% higher incidence of upper respiratory tract infection in the patients who received levacetylleucine (10%) compared with placebo (5%). Additionally, the patients who received levacetylleucine (7%) had an 8% lower incidence of falls in comparison with those who received placebo (15%). Notably, epilepsy occurred only once in a patient that received levacetylleucine. Overall, authors noted no serious AEs occurred related to levacetylleucine or placebo. One death was reported because of aspiration pneumonia after a preplanned placement of a percutaneous endoscopic gastrostomy tube, which was not related to the treatment in the trial.
“This is the second treatment the FDA has approved for NPC within the span of a week. Today’s action further underscores the agency’s commitment to support development of new treatments for rare diseases,” Janet Maynard, MD, MHS., director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, in the FDA’s Center for Drug Evaluation and Research, said in a statement.2 “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.”
