FDA approves levacetylleucine as first treatment for ataxia in ataxia-telangiectasia

The FDA has approved levacetylleucine (Aqneursa; IntraBio) to treat ataxia in adults and pediatric patients with ataxia-telangiectasia (A-T) who weigh at least 15 kg. It is the first therapy approved for this inherited neurodegenerative disorder.¹ The approval rests on a 73-patient randomized crossover trial in which patients scored better on a functional ataxia scale during active treatment than during placebo.¹

Franziska Hoche, MD, assistant professor of neurology at Mass General Research Institute and principal investigator, called the trial results a "major scientific and clinical milestone" when topline findings were released in January.²

Levacetylleucine trial design and fSARA results in ataxia-telangiectasia

The trial (NCT06673056) was randomized, double-blind, placebo-controlled, and used a two-period crossover design with 12 weeks per period. It enrolled 73 patients aged 4 years or older with confirmed A-T (26 adults, 47 pediatric patients). Median age at treatment initiation was 13 years (range, 4-50), and 70 patients (96%) completed the study.¹

Efficacy was assessed with the functional Scale for Assessment and Rating of Ataxia (fSARA). This modified tool scores gait, sitting, stance, and speech from 0 (best) to 16 (worst).¹ The FDA reported that patients scored better on levacetylleucine than on placebo but did not publish an effect size.¹ In sponsor-reported topline data using the full SARA, scores improved by 1.92 points with treatment vs 0.14 with placebo (between-group difference, −1.88; P < .001). Secondary end points on the International Cooperative Ataxia Rating Scale and the Investigator's Clinical Global Impression of Improvement also favored treatment.²,³

Levacetylleucine safety, adverse reactions, and drug interactions

There are no contraindications, though animal data suggest the drug may cause fetal harm. The most common adverse reactions in A-T were fall, skin laceration, and urinary tract infection.¹ Concurrent use with N-acetyl-DL-leucine should be avoided, and patients taking P-glycoprotein substrates need closer monitoring for related adverse reactions.¹ The sponsor reported no drug-related serious adverse events.²

Ataxia-telangiectasia disease burden and unmet need

A-T is caused by mutations in the ATM gene. It produces progressive loss of coordination that typically begins in early childhood, along with telangiectasias, immune deficiency, and elevated cancer risk.¹ There is no cure, and options for neurologic symptoms have been limited.¹ Estimated prevalence is roughly 1 in 40,000 to 100,000.⁴ A separate phase 3 trial of dexamethasone sodium phosphate encapsulated in autologous erythrocytes (NEAT) failed to meet its primary and key secondary endpoints earlier this year.⁴

Levacetylleucine background and prior approval in Niemann-Pick disease type C

The FDA approved levacetylleucine in 2024 for neurologic manifestations of Niemann-Pick disease type C (NPC) in patients weighing at least 15 kg.¹ That approval drew on a 12-week crossover trial of 60 patients, with an fSARA treatment difference of −0.4 (95% CI, −0.7 to −0.2; P < .001).³ The A-T indication received Orphan Drug designation and Priority Review.¹ The FDA announcement does not describe the drug's mechanism of action in A-T.

A small phase 2 extension study of 12 patients showed a mean SARA change of −2.25 points at 12 months. Scores rose by a mean of 1.36 points during washout (P = .25).³

References

1. US Food and Drug Administration. FDA approves therapy to treat ataxia in patients with ataxia-telangiectasia, a rare genetic disorder. Published September 18, 2026. Accessed September 18, 2026. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-therapy-treat-ataxia-patients-ataxia-telangiectasia-rare-genetic-disorder

2. IntraBio announces positive pivotal trial results of levacetylleucine for the treatment of ataxia-telangiectasia. News release. IntraBio Inc; January 21, 2026. Accessed September 18, 2026. https://businesswire.com/news/home/20260121091020/en/IntraBio-Announces-Positive-Pivotal-Trial-Results-of-Levacetylleucine-for-the-Treatment-of-Ataxia-Telangiectasia

3. IntraBio Announces Submission of Supplemental New Drug Application for Levacetylleucine for Ataxia-Telangiectasia. News release. IntraBio. March 20, 2026. Accessed Sepember 18, 2026. https://www.businesswire.com/news/home/20260320451208/en/IntraBio-Announces-Submission-of-Supplemental-New-Drug-Application-for-Levacetylleucine-for-Ataxia-Telangiectasia

4. Phase 3 win for modified amino acid in rare ataxia-telangiectasia. Medscape Medical News. May 5, 2026. Accessed September 18, 2026. https://www.medscape.com/viewarticle/phase-3-win-modified-amino-acid-rare-ataxia-telangiectasia-2026a1000e7q