Aqneursa

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder caused by mutations in the ATM gene. It causes progressive loss of muscle control and coordination (ataxia) that typically begins in early childhood, small dilated blood vessels (telangiectasias), immune deficiencies, and an elevated risk of cancer. A 2022 systematic review found no population-based prevalence study, and published estimates differ by source. GeneReviews gives an estimated prevalence of 1 to 9 per 100,000 and a reported incidence between 1 in 300,000 and 1 in 40,000. MedlinePlus Genetics gives 1 in 40,000 to 100,000 people worldwide. A European Respiratory Society statement gives 1 per 150,000 in Europe and 3 per million in the United Kingdom, and the Ataxia-Telangiectasia Society estimates approximately 170 cases in the United Kingdom and Ireland, a prevalence of approximately 1 in 400,000. IntraBio stated 1 in 40,000, 1 in 40,000 to 100,000, and approximately 1 in 70,000 in three releases during 2026. In the United States, approximately 350 children are known to the A-T Children's Project, and Quince Therapeutics, the developer of another investigational A-T treatment, cites approximately 4,600 diagnosed people from IQVIA claims data.

In classic A-T, ataxia first appears in the toddler years and most children use a wheelchair from about age 10 years. In a cohort of 57 individuals with variant A-T, 42 used a wheelchair, first obtained at a median age of 20 years. Median survival was 25 years in a prospective U.S. cohort and 19 years in a retrospective U.S. cohort. The Kaplan-Meier 20-year survival rate was 53.4% in a French cohort of 240 individuals and 52.6% in a Latin American cohort of 218 individuals. Chronic lung disease and cancer each account for about one-third of deaths, and GeneReviews states that most individuals with classic A-T do not live longer than age 30 years.

Before September 2026, no treatment was approved for A-T in any country. Published guidance recommends symptomatic and supportive care from a multidisciplinary team that includes neurology, pulmonology, immunology, rehabilitation medicine, nutrition, and physical, occupational, and speech-language therapy, and states that no treatment is known to slow or stop the neurological decline. A 2026 systematic review of 13 studies with 314 participants concluded that no intervention had demonstrated sustained efficacy in adequately powered controlled trials.

• Design: IB1001-303 (NCT06673056, Trial 2 in the prescribing information) was a phase 3, randomized, double-blind, placebo-controlled, two-period crossover trial at ten research hospitals in Germany, Slovakia, Spain, Switzerland, the United Kingdom, and the United States. It randomized 73 participants aged 4 to 50 years (47 pediatric and 26 adult) with genetically confirmed A-T and a SARA score of 7 to 34 to levacetylleucine followed by placebo (36 participants) or placebo followed by levacetylleucine (37 participants), with 12 weeks of each treatment at 2 g, 3 g, or 4 g per day by body weight. Seventy participants (96%) completed the study. The crossover was immediate, with no washout between the periods; the protocol states that its analysis method does not require a washout, and the publication describes the placebo period that followed levacetylleucine as having served as a washout.
• Efficacy in the U.S. prescribing information: the primary efficacy outcome was the functional SARA (fSARA), which rescores the gait, sitting, stance, and speech disturbance domains of the SARA to a total of 0 to 16, with higher scores indicating worse neurological status. The least squares mean fSARA total score was 7.2 on levacetylleucine and 7.8 on placebo, a treatment effect of -0.6 (95% CI -0.9 to -0.2; two-sided p = 0.0013).
• Efficacy in the publication: the protocol primary endpoint was the SARA total score, on which the maximum is 40. The mean change was -1.92 (SD 2.81) on levacetylleucine and -0.14 (SD 2.38) on placebo, a linear mixed model treatment effect of -1.88 (95% CI -2.70 to -1.06; p<0.0001). Treatment effects on secondary endpoints were -2.84 (95% CI -4.87 to -0.81) on the ICARS and 0.01 (95% CI -0.06 to 0.07) on the SCAFI; no adjustment for multiple comparisons was prespecified, and the publication states that no definite conclusions can be drawn from the secondary endpoints. Participants assigned to levacetylleucine first had a mean SARA increase of 1.81 (SD 3.12) during the placebo period that followed.
• Safety: in the prescribing information, the adverse reactions in Treatment Period I with an incidence of at least 5% and greater than placebo were fall (2 of 36 participants, 6%, on levacetylleucine and 1 of 37, 3%, on placebo), skin laceration (2 of 36, 6%, and 0 of 37), and urinary tract infection (2 of 36, 6%, and 1 of 37, 3%). The publication reports 54 adverse events in 29 participants on levacetylleucine and 75 adverse events in 25 participants on placebo, no treatment-related serious adverse events or deaths, and three withdrawals after serious adverse events assessed as unrelated to treatment (acute T-cell leukemia, diffuse large B-cell lymphoma, and a lower respiratory tract infection). The label lists no contraindications and one warning, embryo-fetal toxicity: in pregnant rats and rabbits, levacetylleucine during organogenesis increased embryo-fetal death and skeletal malformations at approximately 1.4-fold and 6-fold, respectively, the maximum recommended human dose of 4 g per day. The label directs verification that a female of reproductive potential is not pregnant before initiation and advises effective contraception during treatment and for 7 days after the last dose.
• Earlier trials of N-acetyl-L-leucine in A-T: a randomized, double-blind, placebo-controlled crossover trial at Ghaem Hospital in Mashhad randomized 16 participants (mean age 9.8 years) to 1 to 4 g per day or placebo for 6 weeks each, separated by a 4-week washout, and found no significant effect on the SARA or on the SCAFI components (p > 0.05). The sponsor's open-label, rater-blinded phase 2 trial IB1001-203 planned approximately 39 participants and was terminated after 17 were enrolled. Its primary endpoint, the Clinical Impression of Change in Severity during treatment minus that during washout, had a mean of 0.16 (SD 1.65) in 16 participants, and the registry posts no statistical test.

No published budget impact model, cost-effectiveness analysis, or health technology assessment of levacetylleucine in A-T has been identified, and no source states a wholesale acquisition cost (WAC) announced with the A-T approval of 18 September 2026. The prices identified are for the 1 gram packet introduced in September 2024. IntraBio reported to California a WAC of $13,450 per carton of 28 packets at introduction on 24 September 2024. An Oklahoma Medicaid review dated February 2025 listed $480.36 per packet, $57,643.20 per 30 days, and $691,718.40 per year at the maximum labeled dose of 4 g per day. Federal prices per carton of 28 packets that started on 1 January 2026 are $13,339.54 on the Federal Supply Schedule and $10,206.02 for the Big Four, and the New York Medicaid list effective 29 September 2026 carries a maximum reimbursable amount of $555.7142800 per packet. A September 2026 news report states a cost of $15,000 every one to two weeks.

The labeled dose is 2 g per day at 15 kg to less than 25 kg, 3 g per day at 25 kg to less than 35 kg, and 4 g per day at 35 kg or more. In the pivotal trial, 18 of 73 participants (25%), 17 (23%), and 38 (52%) were in those weight bands. For the eligible population, IntraBio states that A-T affects an estimated 1 in 40,000 people, and Quince Therapeutics cites approximately 4,600 diagnosed people with A-T in the United States from IQVIA claims data; IntraBio estimated 200 people in the United States with Niemann-Pick disease type C (NPC) in its California filing for the 2024 introduction. National Medicaid data for the first quarter of 2026, which precedes the A-T approval, record 7,728 units and $4,017,756.66 reimbursed under fee-for-service and 6,076 units and $3,160,527.34 under managed care. An Oregon Medicaid evaluation in NPC dated December 2025 listed levacetylleucine among medications proposed for a carve-out of products with an estimated acquisition cost of more than $500,000 per member over 12 months.

The FDA approved levacetylleucine on 18 September 2026 for ataxia in adults and pediatric patients with A-T weighing at least 15 kg and describes it as the first treatment approved for ataxia in A-T. The evidence is one randomized, double-blind, placebo-controlled crossover trial of 73 participants with 12 weeks of each treatment. The prescribing information reports a treatment effect of -0.6 (95% CI -0.9 to -0.2) on the 16-point fSARA, and the publication reports a treatment effect of -1.88 (95% CI -2.70 to -1.06) on the 40-point SARA, the protocol primary endpoint. The prescribing information gives no numerical SARA result and states that the fSARA results were supported by consistent results on the original SARA. Adverse reactions with an incidence of at least 5% and greater than placebo were fall, skin laceration, and urinary tract infection; the label has no contraindications and one warning, embryo-fetal toxicity.

The controlled comparison covers 12 weeks of treatment. Participants who crossed from levacetylleucine to placebo had a mean SARA increase of 1.81 points over the following 12 weeks, and efficacy and safety beyond 12 weeks depend on the open-label extension phase, which was ongoing at publication. Eligibility required an age of 4 years or older and a SARA score of 7 to 34, and 55 of 73 participants (75%) were White. The investigators state that the study was too short to investigate effects on immunological defects and oncological risks. An earlier randomized crossover trial in 16 participants found no significant effect of N-acetyl-L-leucine on the SARA, and the phase 2 trial IB1001-203 was terminated after 17 of approximately 39 planned participants were enrolled. No cost-effectiveness analysis, budget impact model, or health technology assessment in A-T has been published, and no source states a WAC announced with the A-T approval; the WAC reported at the 2024 introduction was $13,450 per carton of 28 packets, and a 2025 state Medicaid review listed $691,718.40 per year at 4 g per day.