Condition
Ataxia-telangiectasia is a rare, inherited neurodegenerative disorder caused by mutations in the ATM gene. It primarily affects the nervous system, causing progressive loss of muscle control and coordination (ataxia) that typically begins in early childhood. The disease also causes small dilated blood vessels (telangiectasias), immune deficiencies, and an elevated risk of cancer. There is no cure for ataxia-telangiectasia, and treatment options for the neurological symptoms of the disease have been limited.
Data Supporting Aqneursa
The effectiveness of Aqneursa was evaluated in a randomized, double-blind, placebo-controlled, two-period crossover study (NCT06673056) of 73 patients aged 4 years or older with a confirmed diagnosis of ataxia-telangiectasia. Patients were randomly assigned to receive Aqneursa followed by placebo, or placebo followed by Aqneursa, with each treatment period lasting 12 weeks. Of the 73 patients (26 adults and 47 pediatric patients), 38 were female and 35 were male. The median age at treatment initiation was 13 years (range: 4 to 50 years). A total of 70 patients (96%) completed the study.
Efficacy was assessed using the functional Scale for Assessment and Rating of Ataxia (fSARA), a modified clinical tool evaluating gait, sitting, stance, and speech disturbance, with scores ranging from 0 (best neurological status) to 16 (worst). When patients were taking Aqneursa, they scored better on the fSARA compared to when these patients were taking placebo and showed significant improvement in neurological function.
Safety Information
There are no contraindications for Aqneursa, although this drug may cause fetal harm based on data from animal studies. The most common adverse reactions in patients with ataxia-telangiectasia were fall, skin laceration, and urinary tract infection.
Aqneursa interacts with N-acetyl-DL-leucine and simultaneous use should be avoided. Patients receiving P-glycoprotein (P-gp) substrates should be monitored more frequently for related adverse reactions when used with Aqneursa.
Designation
Aqneursa received Orphan Drug designation and Priority Review for the ataxia-telangiectasia indication. Approval was granted to IntraBio Inc.
https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-therapy-treat-ataxia-patients-ataxia-telangiectasia-rare-genetic-disorder
Martakis K, Bremova-Ertl T, Bolton C, Foltan T, Del Mar Garcia Romero M, Gautschi M, Han V, Hahn A, Kolnikova M, Panagioti O, Perlman S, Prasad M, Schmahmann J, Skorvanek M, Thakur N, Thiel M, Hoche F. Safety and efficacy of levacetylleucine in ataxia-telangiectasia: a phase 3, randomised, double-blind, placebo-controlled crossover trial. Lancet Neurol. 2026 Jul;25(7):633-644. doi: 10.1016/S1474-4422(26)00158-4. PMID: 42309084.
Abstract
Background: Ataxia-telangiectasia is a rare, autosomal recessive neurodegenerative disorder. Levacetylleucine (N-acetyl-L-leucine) has been shown to be efficacious for the treatment of neurological manifestations and to have a disease-modifying effect in lysosomal storage disorders such as Niemann-Pick disease type C. We aimed to assess the safety and efficacy of levacetylleucine for paediatric and adult patients with ataxia-telangiectasia.
Methods: In this phase 3, randomised, double-blind, placebo-controlled crossover trial, participants were enrolled across ten research hospitals in Germany, Slovakia, Spain, Switzerland, the UK, and the USA. Eligible patients aged 4 years or older with genetically confirmed ataxia-telangiectasia were randomly assigned (1:1) using interactive response technology to receive two or three times daily orally administered levacetylleucine or a matching placebo over two consecutive 12-week treatment periods (patients weighing 35 kg or more received 4 g per day of orally administered levacetylleucine or a matching placebo three times per day and patients weighing less than 35 kg received weight-tiered doses two or three times per day based on approximately 0·1 g/kg per day). All participants, investigators, and assessors were blinded to group assignment. The primary outcome was the mean change on the Scale for the Assessment and Rating of Ataxia (SARA), assessed at baseline and at the end of each 12-week treatment period of levacetylleucine or placebo. Safety and efficacy analyses were done in all randomly assigned patients who received at least one dose of study medication, and a linear mixed-effects model was used to account for data missing at random. The trial is registered with ClinicalTrials.gov, NCT06673056, and CTIS, 2024-517706-29; the open-label extension phase is ongoing.
Findings: Between March 18, 2025 and June 30, 2025, 77 participants with a genetically confirmed diagnosis of ataxia-telangiectasia were screened for inclusion. Four patients were excluded (not meeting inclusion criteria) and 73 were enrolled and randomly assigned (36 to levacetylleucine followed by placebo and 37 to placebo followed by levacetylleucine. 73 patients were included in the primary analysis and safety sets. 38 (52%) of 73 patients were female and 35 (48%) were male; 55 (75%) of 73 patients were White. 47 (64%) of 73 were younger than 18 years and 26 (36%) were aged 18 years or older. The mean change in the SARA total score with levacetylleucine was -1·92 (SD 2·81) versus -0·14 (2·38) with placebo (linear mixed model treatment effect -1·88 [SD 0·41], 95% CI -2·70 to -1·06; p<0·0001). 54 adverse events occurred in 29 patients receiving levacetylleucine versus 75 events in 25 patients receiving placebo. No treatment-related serious adverse events or deaths occurred.
Interpretation: Levacetylleucine showed a significant and clinically meaningful improvement in functioning and was safe and well-tolerated, providing a favourable benefit-risk profile for the treatment of ataxia-telangiectasia. An ongoing open-label extension phase of this trial will investigate potential long-term, neuroprotective and disease-modifying effects.
Funding: IntraBio.
No comments:
Post a Comment