Review section

Field	Value
Drug	Aqneursa (levacetylleucine)
Indication reviewed	Ataxia in adults and pediatric patients with ataxia-telangiectasia weighing at least 15 kg
Therapeutic category	Modified amino acids
Manufacturer	IntraBio Inc.
Regulatory status	Approved for this indication September 18, 2026
Data as of	October 2, 2026
Prepared by	To be completed by the reviewing plan
Review status	Draft for pharmacy and therapeutics committee review

Indications

Table 1. FDA-approved indications

Indications	Aqneursa (levacetylleucine)
“treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adults and pediatric patients weighing ≥15 kg”	✓
“treatment of ataxia in adults and pediatric patients with ataxia-telangiectasia (A-T) weighing ≥15 kg”	✓

Weight limit and age range of the indications

“The safety and effectiveness of AQNEURSA for the treatment of ataxia in patients with A-T have been established in 47 pediatric patients weighing ≥ 15 kg in Trial 2” (opens the prescribing information at this quote)
“The safety and effectiveness of AQNEURSA for the treatment of NPC have been established in 23 pediatric patients weighing ≥15 kg in Trial 1.” (opens the prescribing information at this quote)
“The safety and effectiveness of AQNEURSA have not been established in pediatric patients weighing <15 kg.” (opens the prescribing information at this quote)
“NPC and A-T are largely diseases of pediatric and young adult patients. Clinical studies of AQNEURSA did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.” (opens the prescribing information at this quote)

Pharmacokinetics

Table 2. Pharmacokinetic parameters

Generic Name(s)	Bioavailability	Protein Binding	Metabolism	Excretion	Half-Life
Levacetylleucine	Not reported	Not reported	“Levacetylleucine is metabolized into acetate and L-leucine by ubiquitously expressed enzymes, which are used endogenously in catabolic and metabolic pathways.”“Cytochrome P450 enzymes are not involved in the metabolism of levacetylleucine.”	Not reported	“Levacetylleucine estimated half-life is around 1 hour”

How the label reports pharmacokinetic values

“Levacetylleucine pharmacokinetic parameters at steady state are presented as mean (SD) unless otherwise specified.” (opens the prescribing information at this quote)

Exposure, absorption, distribution, and clearance

“Levacetylleucine maximum concentration (Cmax) and area under the curve from time 0 to 24 hours (AUC0-24hrs) were 8.3 (3.3) µg/mL and 33.2 (12.5) h*µg/mL. No levacetylleucine accumulation occurs after repeated administration.” (opens the prescribing information at this quote)
“Levacetylleucine time to Cmax (Tmax) is 1 hour (ranging from 0.5 to 2.5 hours).” (opens the prescribing information at this quote)
“Levacetylleucine apparent (oral) volume of distribution (Vss/F) is 253 (125) L.” (opens the prescribing information at this quote)
“Levacetylleucine estimated half-life is around 1 hour and the apparent (oral) clearance is 139 (59) L/h.” (opens the prescribing information at this quote)

Specific populations and body weight

“No clinically significant differences in pharmacokinetics of levacetylleucine were observed based on age (range 4 to 67 years), gender (female 47%, male 53%), or race/ethnicity (White 92%, Asian 3%, Other or not specified 5%). The effect of renal impairment, hepatic impairment, or pregnancy on levacetylleucine pharmacokinetics is unknown.” (opens the prescribing information at this quote)
“The volume of distribution and clearance of levacetylleucine increases with increasing body weight (21 kg to 109 kg), but these effects on pharmacokinetics are minimized by the recommended weight-based dosing.” (opens the prescribing information at this quote)

Mechanism of action and exposure-response

“The distinct molecular target for levacetylleucine in the treatment of NPC or A-T is unknown.” (opens the prescribing information at this quote)
“Clinical pharmacodynamic studies have not been conducted for levacetylleucine. A relationship was not observed between increasing levacetylleucine exposure and clinical efficacy. The time course of pharmacodynamic response is unknown.” (opens the prescribing information at this quote)

Drug interactions

Table 3. Major drug interactions

Generic Name(s)	Interaction	Mechanism
Levacetylleucine	N-acetyl-DL-leucine and N-acetyl-D-leucine	“Avoid concomitant use of AQNEURSA with N-acetyl-DL-leucine and N-acetyl-D-leucine.”“The D-enantiomer, N-acetyl-D-leucine, competes with levacetylleucine for monocarboxylate transporter uptake, which may reduce the levacetylleucine efficacy.”
Levacetylleucine	P-gp transporter substrates	“Monitor more frequently for P-gp substrate related adverse reactions when used concomitantly with AQNEURSA.”“Levacetylleucine inhibits P-gp”“However, the clinical significance of this finding has not been fully characterized.”
Levacetylleucine	CYP450 enzyme substrates and transporter substrates (in vitro)	“Levacetylleucine does not inhibit CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4 and does not induce CYP 1A2, 2B6, or 3A4.”“Levacetylleucine is a substrate of organic anion transporter (OAT)1 and OAT3, but not organic cation transporter (OCT)2, breast cancer resistance protein (BCRP), or P-glycoprotein (P-gp).”“Levacetylleucine inhibits P-gp, BCRP, bile salt export pump (BSEP), OAT1 and OAT3, but does not inhibit organic anion transporting polypeptide (OATP)1B1 and OATP1B3.”

Abbreviations: BCRP=breast cancer resistance protein; BSEP=bile salt export pump; CYP=cytochrome P450; OAT=organic anion transporter; OATP=organic anion transporting polypeptide; OCT=organic cation transporter; P-gp=P-glycoprotein

Adverse drug events

Table 4a. Adverse drug events reported in 5% or more of patients with ataxia-telangiectasia in Treatment Period I of Trial 2

Adverse Event	Aqneursa (N = 36), n (%)	Placebo (N = 37), n (%)
Fall	“2 (6)”	“1 (3)”
Skin laceration	“2 (6)”	“0 (0)”
Urinary tract infection	“2 (6)”	“1(3)”

Table 4b. Adverse drug events reported in 5% or more of patients with Niemann-Pick disease type C in Treatment Period I of Trial 1

Adverse Event	Aqneursa (N = 30), n (%)	Placebo (N = 30), n (%)
Upper respiratory tract infection	“5 (17)”	“1 (3)”
Abdominal pain	“2 (7)”	“0 (0)”
Dysphagia	“2 (7)”	“0 (0)”
Vomiting	“2 (7)”	“0 (0)”

Trials and treatment duration in the safety evaluation

“The safety of AQNEURSA was evaluated in Trial 2, which included a total of 73 patients with ataxia-telangiectasia (A-T) in a placebo-controlled, randomized, crossover trial” (opens the prescribing information at this quote)
“The mean (SD) treatment duration of AQNEURSA was 84.5 (11.2) days (9 min, 97 max); the mean (SD) treatment duration on placebo was 85.5 (3.6) days (77 min, 94 max).” (opens the prescribing information at this quote)
“Table 3 summarizes common adverse reactions that occurred in patients who were treated with AQNEURSA in Treatment Period I of Trial 2.” (opens the prescribing information at this quote)
“The safety of AQNEURSA was evaluated in Trial 1, which included a total of 60 patients with Niemann-Pick disease Type C (NPC), in a placebo-controlled, randomized, crossover trial” (opens the prescribing information at this quote)
“The mean (SD) treatment duration of AQNEURSA was 86.2 (4.7) days (69 min, 97 max); the mean (SD) treatment duration on placebo was 87.3 (4.8) days (78 min, 113 max).” (opens the prescribing information at this quote)
“Table 2 summarizes adverse reactions that occurred in patients who were treated with AQNEURSA in Treatment Period I of Trial 1.” (opens the prescribing information at this quote)

Most common adverse reactions

“In A-T, the most common adverse reactions (incidence ≥5% and greater than placebo) are fall, skin laceration, and urinary tract infection.” (opens the prescribing information at this quote)
“In NPC, the most common adverse reactions (incidence ≥5% and greater than placebo) are abdominal pain, dysphagia, upper respiratory tract infections, and vomiting.” (opens the prescribing information at this quote)

Laboratory findings

“Thrombocytopenia with platelets < 100 10^3 cells/µL was observed in one patient during Trial 2. The patient had thrombocytopenia at baseline, which decreased further during the trial while the patient was receiving placebo.” (opens the prescribing information at this quote)
“Thrombocytopenia with platelets < 100 10^3 cells/µL was observed in four patients during Treatment Period 1 of Trial 1, all of whom were receiving miglustat for 42 days or longer at the time of enrollment. In two of these patients, the thrombocytopenia was present at baseline. In the other two patients, the thrombocytopenia developed during Trial 1.” (opens the prescribing information at this quote)

Rosacea in Trial 1

“One patient experienced an exacerbation of rosacea during Trial 1 that responded to treatment. AQNEURSA was not discontinued.” (opens the prescribing information at this quote)

Embryo-fetal toxicity warning

“Based on findings from animal reproduction studies, AQNEURSA may cause embryo-fetal harm when administered during pregnancy. Administration of levacetylleucine to pregnant rats and rabbits during the period of organogenesis caused an increase in embryo-fetal death (post implantation loss/resorption) and skeletal malformations at a dose that was approximately 1.4-fold and 6-fold, respectively, the maximum recommended human dose (MRHD) of 4 g/day of levacetylleucine (based on body surface area).” (opens the prescribing information at this quote)
“The decision to continue or discontinue AQNEURSA treatment during pregnancy should consider the female’s need for AQNEURSA, the potential drug-related risks to the fetus, and the potential adverse outcomes from untreated maternal disease.” (opens the prescribing information at this quote)
“For females of reproductive potential, verify that the patient is not pregnant prior to initiating treatment with AQNEURSA. Advise females of reproductive potential to use effective contraception during treatment with AQNEURSA and for 7 days after the last dose if AQNEURSA is discontinued” (opens the prescribing information at this quote)

Pregnancy and lactation

“In animal reproduction studies, an increase in embryo-fetal death (post implantation loss/resorption), decrease in fetal body weight, and increase in external and skeletal malformations were observed in rats and rabbits when levacetylleucine was administered in pregnant rats and rabbits during the period of organogenesis. These effects were observed in rats and rabbits at the doses that were approximately 1.4-fold and 6-fold, respectively, the maximum recommended human dose (MRHD) in patients taking 4 grams of AQNEURSA per day” (opens the prescribing information at this quote)
“There are no available data on AQNEURSA use in pregnant females to evaluate a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Advise a pregnant female of the potential risk to the fetus.” (opens the prescribing information at this quote)
“The background risk of major birth defects and miscarriage for the indicated population is unknown.” (opens the prescribing information at this quote)
“There are no data on the presence of levacetylleucine or its metabolites in either human or animal milk, the effects on the breastfed infant or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for AQNEURSA and any potential adverse effects on the breastfed infant from levacetylleucine or from the underlying maternal condition.” (opens the prescribing information at this quote)

Dosing and administration

Table 5. Usual dosing regimens

Generic Name	Usual Adult Dose	Usual Pediatric Dose	Availability
Levacetylleucine	“The recommended dosage of AQNEURSA to be administered orally, with or without food, is based on the patient’s actual body weight (kg), as shown in Table 1”Body weight: “15 kg to less than 25 kg”Morning dose: “1 gram”Afternoon dose: “No Dose”Evening dose: “1 gram”Body weight: “25 kg to less than 35 kg”Morning dose: “1 gram”Afternoon dose: “1 gram”Evening dose: “1 gram”Body weight: “35 kg or more”Morning dose: “2 grams”Afternoon dose: “1 gram”Evening dose: “1 gram”“For AQNEURSA doses of 2 grams, prepare two packets individually”	“The safety and effectiveness of AQNEURSA for the treatment of ataxia in patients with A-T have been established in 47 pediatric patients weighing ≥ 15 kg in Trial 2”“The recommended dosage of AQNEURSA to be administered orally, with or without food, is based on the patient’s actual body weight (kg), as shown in Table 1”Body weight: “15 kg to less than 25 kg”Morning dose: “1 gram”Afternoon dose: “No Dose”Evening dose: “1 gram”Body weight: “25 kg to less than 35 kg”Morning dose: “1 gram”Afternoon dose: “1 gram”Evening dose: “1 gram”Body weight: “35 kg or more”Morning dose: “2 grams”Afternoon dose: “1 gram”Evening dose: “1 gram”“The safety and effectiveness of AQNEURSA have not been established in pediatric patients weighing <15 kg.”	“For oral suspension: 1 gram levacetylleucine as white to off-white strawberry flavored granules in a unit-dose packet.”“One AQNEURSA packet contains 1 gram levacetylleucine.”“NDC 83853-101-01: Carton containing 28 unit-dose packets”

See the current prescribing information for full details.

Recommended dosage by body weight

Patient's Body Weight	Morning Dose	Afternoon Dose	Evening Dose
“15 kg to less than 25 kg”	“1 gram”	“No Dose”	“1 gram”
“25 kg to less than 35 kg”	“1 gram”	“1 gram”	“1 gram”
“35 kg or more”	“2 grams”	“1 gram”	“1 gram”

Pregnancy status before initiation and contraception

“For females of reproductive potential, verify that the patient is not pregnant” (opens the prescribing information at this quote)
“For a female of reproductive potential, verify that the patient is not pregnant prior to initiating treatment with AQNEURSA.” (opens the prescribing information at this quote)
“Advise a female of reproductive potential to use effective contraception during treatment and for 7 days after the last dose if AQNEURSA is discontinued.” (opens the prescribing information at this quote)

Missed dose

“If a dose of AQNEURSA is missed, skip the missed dose and take the next dose at the scheduled time. Do not take 2 doses at the same time to make up for a missed dose.” (opens the prescribing information at this quote)

Preparation and oral administration

“For oral administration, administer AQNEURSA as follows:” (opens the prescribing information at this quote)
“1. Obtain the required number of AQNEURSA packets for the prescribed dose (one or two packets).” (opens the prescribing information at this quote)
“2. Open and empty the entire contents of one AQNEURSA packet into a container with 40 mL of water, orange juice, almond milk, or yogurt. Do not use hot liquid.” (opens the prescribing information at this quote)
“3. Stir to form a suspension.” (opens the prescribing information at this quote)
“4. Swallow the suspension immediately (within 30 minutes).” (opens the prescribing information at this quote)
“5. For doses requiring two AQNEURSA packets, repeat steps 2 to 4.” (opens the prescribing information at this quote)
“6. Discard unused AQNEURSA suspension if not administered within 30 minutes.” (opens the prescribing information at this quote)

Gastrostomy tube administration

“For patients who have a G-tube (French size 12 or larger) in place, administer AQNEURSA as follows:” (opens the prescribing information at this quote)
“1. Prepare AQNEURSA suspension immediately before administration via gastrostomy tube.” (opens the prescribing information at this quote)
“2. Obtain the required number of AQNEURSA packets for the prescribed dose (one or two packets).” (opens the prescribing information at this quote)
“3. Open and empty the entire contents of one AQNEURSA packet into a container with 40 mL of water ONLY. Do not use hot liquid.” (opens the prescribing information at this quote)
“4. Stir to form a suspension.” (opens the prescribing information at this quote)
“5. Draw up the suspension into a catheter tip syringe.” (opens the prescribing information at this quote)
“6. Administer the suspension immediately through the G-tube.” (opens the prescribing information at this quote)
“7. Flush any residual suspension in the catheter tip syringe with an additional 20 mL of water.” (opens the prescribing information at this quote)
“8. Flush the G-tube again, as needed, until no residual suspension is left in the syringe or feeding tube.” (opens the prescribing information at this quote)
“9. For doses requiring two AQNEURSA packets, repeat steps 3 to 8.” (opens the prescribing information at this quote)
“10. Discard unused AQNEURSA suspension if not administered immediately.” (opens the prescribing information at this quote)

How supplied and storage

“AQNEURSA (levacetylleucine) for oral suspension is supplied as white to off-white granules in a unit-dose multi-layer aluminum/polyethylene packet. Each packet contains 1.7 gram white to off-white granules, equivalent to 1 gram levacetylleucine.” (opens the prescribing information at this quote)
“Each packet of AQNEURSA granules contains 1 gram levacetylleucine and the inactive ingredients hypromellose, isomalt and strawberry flavor.” (opens the prescribing information at this quote)
“Store AQNEURSA at room temperature between 20°C to 25°C (68°F to 77°F); excursion permitted between 15°C to 30°C (59°F to 86°F)” (opens the prescribing information at this quote)

Effectiveness

Table 6. Comparative clinical trials

Study and Drug Regimen	Study Design and Demographics	Study Size and Duration	End Points	Results
Trial 2 (NCT06673056): “Treatment Sequence 1 (N=36): AQNEURSA in Treatment Period I, followed by immediate crossover to placebo in Treatment Period II”“Treatment Sequence 2 (N=37): placebo in Treatment Period I, followed by immediate crossover to AQNEURSA in Treatment Period II.”“AQNEURSA and placebo were administered orally with or without food for 12 weeks in each period. Patients weighing ≥35 kg received 4 gram per day (as 2 gram morning dose, 1 gram afternoon dose, and 1 gram evening dose). The AQNEURSA dosage in patients weighing under 35 kg was based on patient’s body weight”	“a randomized, double-blind, placebo-controlled, two-period crossover study that evaluated the efficacy of AQNEURSA in 73 patients (Trial 2; NCT06673056)”“To be eligible for the study, patients had to be aged 4 years or older with a confirmed diagnosis of A-T. Patients were required to have at least mild ataxia at baseline. Ataxia may be comprised of multiple signs and symptoms, including gait ataxia, truncal ataxia, oculomotor ataxia, and difficulties with balance, speech, and hand coordination.”“Patients were assessed over a 2-week baseline period. Patients were then randomized in a 1:1 ratio to one of the two treatment sequences:”“Of the 73 randomized 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). 75% of the patients were White, 6% Asian, 1% Native Hawaiian or other Pacific Islander, 12% Not Reported, and 6% Other.”	“evaluated the efficacy of AQNEURSA in 73 patients”“Seventy patients (96%) completed the study and received both placebo and AQNEURSA.”“12 weeks in each period”“The fSARA score was assessed at baseline, 6 weeks, 12 weeks (the end of Period I), 18 weeks, and 24 weeks (the end of Period II).”	“Efficacy was demonstrated using a modified version of the SARA, referred to as the functional SARA (fSARA)”“The SARA is a clinical assessment tool that assesses gait, stability, speech, and upper and lower limb coordination across 8 individual domains. The fSARA consists only of gait, sitting, stance, and speech disturbance domains of the original SARA with modifications to the scoring responses. Each domain was rescored from 0 to 4, where 0 is the best neurological status and 4 the worst, with a total score ranging from 0 to 16.”	“The Least Squares Mean fSARA total score was 7.2 when patients were treated with AQNEURSA and 7.8 when patients were treated with placebo. The Least Squares treatment effect for the fSARA total score was -0.6 (95% CI: -0.9, -0.2)”Least squares mean fSARA score (SE), Aqneursa: “7.2 (0.1)”Least squares mean fSARA score (SE), placebo: “7.8 (0.1)”Treatment difference (95% CI): “-0.6 (-0.9, -0.2)”“Two-sided p-value = 0.0013”Treatment Sequence 1 (Aqneursa then placebo), fSARA total score, baseline (N = 36), mean (SD): “7.3 (2.6)”Period I (N = 34), mean (SD): “6.6 (2.8)”Period II (N = 35), mean (SD): “7.0 (3.1)”Treatment Sequence 2 (placebo then Aqneursa), fSARA total score, baseline (N = 37), mean (SD): “8.5 (2.5)”Period I (N = 37), mean (SD): “8.5 (2.6)”Period II (N = 35), mean (SD): “7.8 (2.7)”“Two patients did not have an assessment at the end of Period I (week 12).”“One patient did not have an assessment at the end of Period II (week 24).”“Two patients did not have an assessment at the end of Period II (week 24).”“Patients who received AQNEURSA in Period I followed by placebo in Period II (Treatment Sequence 1) showed a greater improvement in the fSARA score while receiving AQNEURSA in Period I with a mean change from baseline of -0.7 (SD 1.0), compared to Period II with a mean change from baseline of -0.2 (1.1). Patients who received placebo in Period I followed by AQNEURSA in Period II (Treatment Sequence 2) had a mean change of 0.0 (0.9) in Period I but experienced greater improvement in the fSARA score while receiving AQNEURSA in Period II with a mean change of -0.6 (1.3).”“Results on the fSARA were supported by consistent results demonstrated on the original SARA.”

Abbreviations: A-T=ataxia-telangiectasia; CI=confidence interval; fSARA=functional Scale for Assessment and Rating of Ataxia; SARA=Scale for Assessment and Rating of Ataxia; SD=standard deviation; SE=standard error

Protocol primary endpoint (SARA total score), for which the prescribing information reports no value

“Scale for the Assessment and Rating of Ataxia” (opens the source at this quote in a new tab)
“The Scale for Assessment and Rating of Ataxia has 8 items that are related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements, and heel-shin test. The range is 0-40 points, with a lower score representing neurological improvement and a higher score representing neurological worsening.” (opens the source at this quote in a new tab)
“End of Period I (week 12) vs. End of Period 2 (week 24)” (opens the source at this quote in a new tab)

“The primary endpoint of the trial evaluated the effect of treatment with levacetylleucine on the Scale for the Assessment and Rating of Ataxia (SARA) compared to placebo after 12 weeks of treatment. Treatment with levacetylleucine demonstrated a statistically significant and clinically meaningful -1.88 point improvement of the SARA score compared to placebo (-1.92 on levacetylleucine vs -0.14 on placebo, p<0.001).” (opens the source at this quote in a new tab)