IntraBio Submits Supplemental New Drug Application for Levacetylleucine to Treat Ataxia-Telangiectasia

IntraBio has announced the submission of a supplemental new drug application (sNDA) to the FDA for levacetylleucine (Aqneursa), a therapy currently approved for neurological manifestations of Niemann-Pick disease type C (NPC). The application seeks to expand its use as a potential treatment for patients with ataxia-telangiectasia (A-T) and marks the first regulatory submission seeking approval of a therapy specifically for the rare neurodegenerative disorder.¹

The sNDA submission is supported by data from the pivotal phase 3 IB1001-303 trial (NCT06673056), a randomized, placebo-controlled, double-blind crossover phase study in which levacetylleucine met its primary end point in pediatric and adult patients with A-T. At 12 weeks, findings showed that treatment with the agent was associated with statistically significant improvement on the change in Scale for the Assessment and Rating of Ataxia (SARA) score, the primary end point, compared with placebo (−1.92 vs −0.14; between-group difference, −1.88; P <.001).²

Phase 3 Secondary Results

The phase 3 study also met its secondary end points, with levacetylleucine-treated patients demonstrating statistically significant improvements on the International Cooperative Ataxia Rating Scale (mean change, −4.22 vs −1.69; P = .003) and the Investigator’s Clinical Global Impression of Improvement (mean change, −0.6 vs −0.2; P = .02) compared with placebo. In addition, the company noted that levacetylleucine was generally well tolerated, and no drug-related serious adverse events were reported, which was consistent with its previously established safety profile.

“This is a breakthrough for patients and families affected by Ataxia-Telangiectasia,” principal investigator Franziska Hoche, MD, assistant professor of neurology at Mass General Research Institute, said in a prior statement.² “A-T is a rare and devastating disorder with no approved treatments. The results from the IB1001-303 trial, demonstrating levacetylleucine significantly improved patients’ neurological symptoms and everyday function, represent a major scientific and clinical milestone, and provide compelling evidence that levacetylleucine has a meaningful impact on A-T patients’ lives.”

Phase 2 Study Findings

Additional context for the phase 3 evaluation of levacetylleucine was enhanced by late-breaking data presented at the 2025 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held October 5-9, in Honolulu, Hawaii, from an extension of the phase 2 IB1001-203 trial (NCT03759678).³ The phase 2 study enrolled patients aged 6 years or older with A-T, and participants who completed the initial trial were eligible to continue treatment in an extension phase. The extension cohort included 12 patients aged 6 to 36 years who remained on levacetylleucine following completion of the parent study.

In the extension phase, the primary end point was change in SARA score from baseline to the end of the first year of levacetylleucine treatment. Exploratory end points included changes in SARA score during a washout period and changes from baseline through the end of the second year of continued treatment.

After 12 months of therapy, the mean change from baseline in SARA score was −2.25 points (SD, 3.16; 95% CI, −4.25 to −0.25; P = .031). During the subsequent washout period, participants (n = 11) experienced a mean increase of 1.36 points in SARA score (SD, 2.04; 95% CI, 0–2.73; P = .25). Seven patients completed an additional year of treatment following washout, with a mean SARA change of −0.33 points compared with the start of the extension phase.

READ MORE: Phase 3 NEAT Trial of EryDex in Ataxia-Telangiectasia Misses Primary and Key Secondary End Points

Previous Approval in NPC

In September 2024, the FDA approved levacetylleucine as a stand-alone treatment for neurological manifestations in NPC among adults and pediatric patients weighing at least 15 kg, marking the second FDA-approved therapy for the condition following arimoclomol (Miplyffa; Zevra Therapeutics). This approval was supported by data from the 12-week phase 3 IB1001-301 trial (NCT05163288), a double-blind, placebo-controlled crossover study involving 60 patients aged 5 to 67 years.⁴

In the phase 3 IB1001-301 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. 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.

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.

Phase 3 Safety Results in NPC

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.

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REFERENCES
1. IntraBio Announces Submission of Supplemental New Drug Application for Levacetylleucine for Ataxia-Telangiectasia. News release. IntraBio. March 20, 2026. Accessed March 20, 2026. https://www.businesswire.com/news/home/20260320451208/en/IntraBio-Announces-Submission-of-Supplemental-New-Drug-Application-for-Levacetylleucine-for-Ataxia-Telangiectasia
2. IntraBio Announces Positive Pivotal Trial Results of Levacetylleucine for the Treatment of Ataxia-Telangiectasia. News release. IntraBio. January 21, 2026. Accessed March 20, 2026. https://www.businesswire.com/news/home/20260121091020/en/IntraBio-Announces-Positive-Pivotal-Trial-Results-of-Levacetylleucine-for-the-Treatment-of-Ataxia-Telangiectasia
3. Patterson M, Zanrucha B, Raymond J, et al. N-acetyl-L-leucine: Findings from the Extension Phase of a Phase II Clinical Trial in Ataxia-Telangiectasia. Presented at: 2025 MDS Congress; October 5-9; Honolulu, Hawaii. LBA-4.
4. IntraBio Announces U.S. FDA Approval of AQNEURSA for the Treatment of Niemann-Pick Disease Type C. News Release. IntraBio. September 25, 2024. Accessed March 20, 2026. https://www.businesswire.com/news/home/20240925347296/en/IntraBio-Announces-U.S.-FDA-Approval-of-AQNEURSA-for-the-Treatment-of-Niemann-Pick-Disease-Type-C