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Aqneursa (levacetylleucine)

Ataxia-telangiectasia

Also known as IB1001
Manufacturer
IntraBio
Last updated
206 sources

Product information and disease descriptionProduct descriptionProduct information

Contraindications/Warnings/Precautions/Adverse effects

19 evidence topics · 5 sources

Warnings and precautions
Contraindications

“None.” (opens the prescribing information at this quote)

“There are no contraindications for Aqneursa, although this drug may cause fetal harm based on data from animal studies.” (opens the source at this quote in a new tab)

Warning: embryo-fetal toxicity

“Based on findings from animal reproduction studies, AQNEURSA may cause embryo-fetal harm when administered during pregnancy.” (opens the prescribing information at this quote)

“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.” (opens the prescribing information at this quote)

“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)

Interpretation of adverse reaction rates from clinical trials

“Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.” (opens the prescribing information at this quote)

Adverse reactions in A-T: safety population and exposure in Trial 2

“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)

“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)

Adverse reactions in A-T at an incidence of 5% or more in Treatment Period I of Trial 2
Adverse reactionAQNEURSA, 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)”
Laboratory findings in A-T: thrombocytopenia in Trial 2

“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)

Adverse reactions in NPC: safety population and exposure in Trial 1

“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)

“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)

Adverse reactions in NPC at an incidence of 5% or more in Treatment Period I of Trial 1
Adverse reactionAQNEURSA, 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)”
Rosacea and thrombocytopenia in NPC 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)

“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.” (opens the prescribing information at this quote)

“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)

Safety information in the FDA approval announcement

“The most common adverse reactions in patients with ataxia-telangiectasia were fall, skin laceration, and urinary tract infection.” (opens the source at this quote in a new tab)

Adverse events in the published report of the A-T phase 3 trial

“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.” (opens the source at this quote in a new tab)

Patient counseling

“Advise the patient and/or caregiver to read the FDA-approved patient labeling (Instructions for Use).” (opens the prescribing information at this quote)

“Advise a female of reproductive potential and caregiver to inform their healthcare provider of a known or suspected pregnancy” (opens the prescribing information at this quote)

Nonclinical toxicology: carcinogenesis, mutagenesis, and impairment of fertility

“Animal studies to evaluate the carcinogenic potential of levacetylleucine have not been conducted.” (opens the prescribing information at this quote)

“Levacetylleucine was not mutagenic or clastogenic in a battery of in vitro and in vivo assays including bacterial reverse mutation (Ames), chromosomal aberration (in human lymphocytes) and mouse micronucleus assays.” (opens the prescribing information at this quote)

“Animal studies to evaluate effects of levacetylleucine on fertility have not been conducted.” (opens the prescribing information at this quote)

“No carcinogenicity studies have been conducted. The carcinogenic risk is unknown.” (opens the source at this quote in a new tab)

“No effect on fertility was seen in rats at doses up to 1 000 mg/kg/day (1.5- to 2.3-fold human exposure).” (opens the source at this quote in a new tab)

Carcinogenicity study commitment and repeat-dose toxicology: European assessment

“Consequently, the Applicant committed to realize the 26-week carcinogenicity study in rasH2 mice and submit the results when available. The submission of the final report for this study is due by 30 June 2027 (MEA).” (opens the source at this quote in a new tab)

“GI was the primary target organ identified for levacetylleucine.” (opens the source at this quote in a new tab)

“The renal toxicity found in male rats is specific to the species and is not relevant for the clinical aspect.” (opens the source at this quote in a new tab)

European Union contraindication and hypersensitivity warning

“Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.” (opens the source at this quote in a new tab)

“Although no patient experienced anaphylactic or hypersensitivity reaction during the clinical studies, anaphylactic and hypersensitivity reactions may occur after administration of levacetylleucine. Immediate discontinuation of Aqneursa and necessary emergency treatment is required if such reactions occur.” (opens the source at this quote in a new tab)

“No hypersensitivity reactions have been observed in clinical trials with levacetylleucine to date. Such reactions remain generally plausible also for levacetylleucine, given that NADLL is the racemic mixture of the enantiomer levacetylleucine and with NADLL events of hypersensitivity reactions have been observed in the clinical setting.” (opens the source at this quote in a new tab)

European Union excipient warning: isomalt and hereditary fructose intolerance

“Each sachet contains 642.2 mg isomalt. Patients with rare hereditary problems of fructose intolerance should not take this medicinal product.” (opens the source at this quote in a new tab)

European Union adverse reaction listing and overdose

“The most common adverse reaction, with a frequency of 1.2%, is flatulence.” (opens the source at this quote in a new tab)

“Adverse reactions observed during the placebo-controlled, randomised, crossover clinical study and the open-label, rater-blinded study, including extension phase, in patients with NPC are based on a total of 84 patients with a median treatment duration of 86 days.” (opens the source at this quote in a new tab)

“In case of overdose, symptomatic treatment is recommended.” (opens the source at this quote in a new tab)

Pooled NPC safety database: European assessment

“From the pooling data, the total observation duration was 52.98 patient-years for the levacetylleucine use group” (opens the source at this quote in a new tab)

“The mean levacetylleucine treatment duration was 229.3 days, with a maximum of 938 days.” (opens the source at this quote in a new tab)

“In the pooled safety data, two-third of patients who received levacetylleucine (65,5% n=55/84) experienced adverse events (AEs), corresponding to 241 events” (opens the source at this quote in a new tab)

“Overall, none of the reported SAEs was considered to be treatment-related by the Applicant, and none resulted in withdrawal of study drug treatment.” (opens the source at this quote in a new tab)

“No signs of withdrawal or rebound have been observed in nonclinical or clinical studies with levacetylleucine.” (opens the source at this quote in a new tab)

Liver enzymes and the European risk management plan

“Presently available data cannot allow any liver toxicity potential to be identified.” (opens the source at this quote in a new tab)

“Therefore, in respect to liver enzymes changes and the uncertainties on levacetylleucine causality, the risk of hepatotoxicity has been added as an important potential risk in the list of safety concerns of the RMP.” (opens the source at this quote in a new tab)

“Hepatotoxicity; Carcinogenicity; Developmental toxicity” (opens the source at this quote in a new tab)