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Aqneursa (levacetylleucine)

Ataxia-telangiectasia

Also known as IB1001
Manufacturer
IntraBio
Last updated
206 sources

Product information and disease descriptionPlace of product in therapyApproaches to treatment

Expected outcomes of therapy

12 evidence topics · 9 sources

Functional SARA after 12 weeks: prescribing information

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

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

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

“Results on the fSARA were supported by consistent results demonstrated on the original SARA.” (opens the prescribing information at this quote)

SARA total score after 12 weeks: trial publication

“The mean change in the SARA score following 12 weeks of treatment was –1·92 (SD 2·81) with levacetylleucine treatment and –0·14 (2·38) with placebo (linear mixed model treatment effect –1·88, SD 0·41; 95% CI –2·70 to –1·06; p<0·0001; table 2).” (opens the source at this quote in a new tab)

Change from baseline on each scale after 12 weeks: trial publication
EndpointLevacetylleucine, mean change (SD)Placebo, mean change (SD)Treatment effect (95% CI)
SARA“−1·92 (2·81)”“−0·14 (2·38)”“−1·88 (−2·70 to −1·06)”
FDA functional SARA“−0·65 (1·16)”“−0·10 (1·02)”“−0·57 (−0·92 to −0·23)”
SCAFI“0·06 (0·28)”“0·04 (0·24)”“0·01 (−0·06 to 0·07)”
ICARS“−4·22 (7·77)”“−1·69 (6·09)”“−2·84 (−4·87 to −0·81)”
Investigator's Clinical Global Impression of Improvement“−0·6 (0·8)”“−0·2 (0·6)”“−0·4 (−0·7 to −0·02)”
Loss of effect after crossover to placebo

“By contrast, patients who received levacetylleucine followed by placebo (n=35) had an increase in SARA score of 1·81 (SD 3·12) during period 2 on placebo, which effectively served as a washout from levacetylleucine, reflecting a deterioration in neurological signs and symptoms when treatment with levacetylleucine was stopped.” (opens the source at this quote in a new tab)

“For patients randomly assigned to sequence 1 (levacetylleucine to placebo), the improvements of levacetylleucine treatment observed in period 1 were lost in period 2 (consistent with the drug's pharmacological and pharmacokinetic action), as patients worsened and returned to their baseline status.” (opens the source at this quote in a new tab)

Participant and caregiver exit interviews

“57 (81%) of 70 exit interviews completed by participants or caregivers reported improvement in patients’ neurological signs and symptoms during the study while on levacetylleucine.” (opens the source at this quote in a new tab)

Time to effect

“Results from the study showed AQNEURSA significantly improved signs and symptoms of ataxia and demonstrated functional benefits important to everyday life that were evident within 12 weeks.” (opens the source at this quote in a new tab)

“The time course of pharmacodynamic response is unknown.” (opens the prescribing information at this quote)

Minimal clinically important difference on SARA: thresholds cited in the trial publication

“for which a 1-point change has been validated as representing a clinically meaningful change in functioning (gain or loss of complex function which is relevant to the patient's everyday life)” (opens the source at this quote in a new tab)

“A sample size of 46 patients was estimated to provide 80% power, at a one-sided significance level of 5%, to detect a true mean difference between groups in the SARA scores of 1·0” (opens the source at this quote in a new tab)

“Multiple studies have investigated a minimally clinically important difference on the SARA scale, ranging from 1 to 1·5 points” (opens the source at this quote in a new tab)

“the mean change on levacetylleucine and the treatment effect with levacetylleucine versus placebo are larger than all reported thresholds” (opens the source at this quote in a new tab)

Minimal clinically important difference on SARA: lysosomal storage disorder trial cohorts

“We analyzed data from three clinical trial cohorts (IB1001-201, IB1001-202, and IB1001-301) of patients with Niemann–Pick disease type C (NPC) and GM2 Gangliosidoses (Tay–Sachs and Sandhoff disease) comprising 122 patients and 703 visits.” (opens the source at this quote in a new tab)

“For the CGI-I responses and change in SARA scores, Area Under the Curve (AUC) values were 0.82, 0.71, and 0.77 for the Investigator’s, Caregiver’s, and Patient’s CGI-I respectively, indicating strong agreement.” (opens the source at this quote in a new tab)

“A 1-point change represents a clinically meaningful transition reflecting the gain or loss of complex function.” (opens the source at this quote in a new tab)

Minimal clinically important difference on SARA: cerebellar ataxia exercise trial

“Sixty‐two individuals with cerebellar ataxias participated in a home‐exercise clinical trial.” (opens the source at this quote in a new tab)

“The MCID for SARA using anchor‐based method was 1.75. The distribution‐based method and distribution‐based mapping identified a median MCID score of 1.23.” (opens the source at this quote in a new tab)

“Synthesizing the methods, we recommend an MCID of 1.5 for SARA, which is slightly higher that what is currently used in clinical trials.” (opens the source at this quote in a new tab)

Meaningful change on the functional SARA: clinician interviews in spinocerebellar ataxia

“For the total f-SARA score, all 8 HCPs regarded minimum meaningful improvements or worsening as a 1- to 2-point change” (opens the source at this quote in a new tab)

Minimal clinically important difference established in ataxia-telangiectasia

No evidence found.

Annual SARA progression in adults with ataxia-telangiectasia

“We analysed longitudinal Scale for the Assessment and Rating of Ataxia (SARA) data from the largest published adult AT cohort to date (n = 82, age > 16 years).” (opens the source at this quote in a new tab)

“Neurological impairment progressed with a mean SARA increase of 0.38 points/year.” (opens the source at this quote in a new tab)

Durability beyond 12 weeks and effects on other disease features

“First, the study was designed to investigate the symptomatic effects of levacetylleucine; data from the ongoing extension phase will provide further insights into its impact on ataxia-telangiectasia disease progression and continued data on the long-term safety of levacetylleucine for ataxia-telangiectasia.” (opens the source at this quote in a new tab)

“Finally, the study duration was not long enough to investigate the effects of levacetylleucine on other key features of ataxia-telangiectasia, such as immunological defects and oncological risks.” (opens the source at this quote in a new tab)

“An ongoing open-label extension phase of this trial will investigate potential long-term, neuroprotective and disease-modifying effects.” (opens the source at this quote in a new tab)

“Patients who have participated in the study may be offered the opportunity to roll over into an Extension Phase, which is planned to allow patients to have further access to IB1001.” (opens the source at this quote in a new tab)