SMA Research Platform

Evidence graph for Spinal Muscular Atrophy

Biology-first target discovery
Christian Fischer / Bryzant Labs
14,766Targets
453Trials
84Drugs
7Datasets
6,987Sources
64,683Claims
72,052Evidence
29,649Hypotheses
DRUGapprovedgene therapy

onasemnogene abeparvovec

Brand names: Zolgensma

Mechanism

AAV9-mediated gene replacement delivering functional SMN1. Single IV infusion.

Approved indications

type1presymptomatic

Related claims (50)

TypePredicateConfSource
drug efficacyOnasemnogene abeparvovec-xioi (Zolgensma) is a costly drug (clinical trial result)80%37003633
survivalOnasemnogene abeparvovec treatment is associated with an event-free survival of 96.5% (95%CI: 90.76 to 99.54, I2 = 32%, n = 66) in patients with SMA type 1 (clinical trial result).69%38713659
motor functionPatients with ≥four SMN2 gene copies treated with onasemnogene abeparvovec monotherapy demonstrated improvements in motor function (observed in patient cohort).65%39260228
safetyHigh vector dose or supraphysiological levels of SMN may cause adverse events such as liver toxicity associated with onasemnogene abeparvovec.65%38413837
survivalOnasemnogene abeparvovec treatment is associated with a global survival of 97.56% (95%CI: 92.55 to 99.86, I2 = 0%, n = 67) in patients with SMA type 1 (clinical trial result).64%38713659
motor functionOnasemnogene abeparvovec treatment is associated with a CHOP-INTEND score ≥ 40 points proportion of 87.28% (95%CI: 69.81 to 97.83, I2 = 69%, n = 67) in patients with SMA type 1 (clinical trial result).64%38713659
gene expressionIntravenous administration of onasemnogene abeparvovec to SMA model mice resulted in sustained expression of survival motor neuron (SMN) protein (observed in mouse model).59%34980814
drug efficacyAt a list price of $2.125 M, onasemnogene abeparvovec is cost-effective compared to nusinersen for SMA1 patients treated before age 2 years.59%33708361
drug efficacySPR1NT trial results suggested that onasemnogene abeparvovec is effective in treating pre-symptomatic SMA (clinical trial result)59%37731145
drug efficacyOnasemnogene abeparvovec (Zolgensma®) was approved for the treatment of patients with SMA with up to three copies of the SMN2 gene or the clinical presentation of SMA type 1.59%32763124
motor functionIntravenous administration of onasemnogene abeparvovec to SMA model mice resulted in improvement of motor function (observed in mouse model).59%34980814
drug efficacyOnasemnogene abeparvovec, a vector-based gene therapy, is an approved therapeutic drug for SMA treatment that improves motor function.59%35352647
drug efficacyFor patients with three SMN2 copies, onasemnogene abeparvovec (OA) was less costly, with a similar efficacy profile compared with nusinersen (clinical trial result).59%40569556
drug efficacyGreatest improvements were seen in subjects who received onasemnogene abeparvovec treatment within 2 months of birth (clinical trial result)59%38223869
drug efficacyIntrathecal onasemnogene abeparvovec administration, at fixed, low doses, may enable treatment of heavier patients ineligible for weight-based intravenous dosing.59%36911944
motor functionSMA I patients treated with onasemnogene abeparvovec show significant improvement on CHOP-INTEND motor assessment over 24 months.59%41854353
drug efficacyChildren treated with onasemnogene abeparvovec have reduced sleep disordered breathing over time.59%37778092
motor functionStabilisation or improvement in bulbar or respiratory function was observed in 20/21 (95.2%) patients treated with onasemnogene abeparvovec (clinical trial result).59%35170254
drug targetGene therapies such as onasemnogene abeparvovec for spinal muscular atrophy (SMA) utilize adeno-associated virus 9 (AAV9) for targeted gene delivery.59%40018025
survivalOnasemnogene abeparvovec showed the highest survival rate (95% [95% CI: 88, 100]) (clinical trial result).59%39604484
drug efficacyEfficacy data on demonstration of motor milestones suggest that Latin American patients with SMA may benefit from onasemnogene abeparvovec treatment (clinical trial result).59%40778350
drug efficacyOnasemnogene abeparvovec-xioi has shown significant efficacy in improving motor function (clinical trial result).59%40630496
drug efficacyThis case series and accompanying literature review reinforce the efficacy and safety of onasemnogene abeparvovec in the treatment of SMA type 1 (observed in patient cohort).59%40630496
drug efficacyOnasemnogene abeparvovec is indicated for the treatment of paediatric patients with spinal muscular atrophy(SMA) with biallelic mutations in the survival motor neuron 1 (SMN1) gene.59%40329332
drug efficacyOnasemnogene abeparvovec provides evidence for sustained clinical durability of the therapeutic dose (clinical trial result).59%33999158
survivalAll children with three SMN2 copies treated with onasemnogene abeparvovec before symptom onset survived without permanent ventilation at 14 months (clinical trial result)59%35715567
motor functionAt 6 months post-dose, 91.5% of infants treated with onasemnogene abeparvovec achieved a clinically significant ≥ 4-point improvement in CHOP INTEND score from baseline (clinical trial result).59%40622452
gene expressionOnasemnogene abeparvovec delivers a functional transgene to restore SMN protein expression.59%35437095
drug efficacyOnasemnogene abeparvovec was efficacious in improving motor functioning in children with SMA (clinical trial result).59%38450080
drug efficacyYounger patients demonstrated superior therapeutic efficacy post-onasemnogene abeparvovec administration (clinical trial result)59%41283841
drug efficacyThe treatment of SMA with nusinersen, onasemnogene abeparvovec, and risdiplam changes the disease phenotype with changes in motor function far exceeding any improvement in respiratory and nutritional function (clinical trial result).59%38905882
drug efficacyPatients receiving onasemnogene abeparvovec as switch therapy after prior treatment show slower motor improvement compared to monotherapy.59%41854353
drug efficacyTherapy with onasemnogene abeparvovec led to an improvement in the clinical picture of the treated subjects (clinical trial result)59%38223869
drug efficacyOnasemnogene Abeparvovec is a potent treatment for SMA leading to significant motor function improvements (observed in patient cohort).59%36855136
drug efficacyNusinersen and onasemnogene abeparvovec treatment is associated with modest motor improvements in a patient with spinal muscular atrophy type 0 (clinical trial result)59%32515646
drug efficacyOnly transitory improvement in functional outcomes was observed after Onasemnogene abeparvovec treatment (observed in patient cohort).59%39111255
motor functionBetter progress in motor function was observed in individuals who received Onasemnogene abeparvovec-xioi (OA) earlier and who were presymptomatic (clinical trial result).59%37149951
motor functionRapid and clinically significant improvements in motor function were observed for onasemnogene abeparvovec-treated patients with symptomatic SMA type 1 (clinical trial result).59%40622452
drug efficacyThe limited dose of onasemnogene abeparvovec did not lead to marked clinical improvement (clinical trial result).59%40705999
drug efficacyThe 2nd-generation vector showed better safety and improved efficacy in SMA mouse model in a head-to-head comparison between the second-generation vector and a benchmark vector, identical in design to onasemnogene abeparvovec.59%38413838
safetyDiverging patterns in adverse reaction reporting suggest a stabilizing safety profile for nusinersen and potential emerging safety signals for risdiplam and onasemnogene abeparvovec.59%41149786
drug efficacyOnasemnogene abeparvovec-xioi has shown significant efficacy in improving survival rates (clinical trial result).59%40630496
biomarkerSMN2 copy number is a predictor of motor improvement in SMA I patients treated with onasemnogene abeparvovec.59%41854353
drug efficacyTherapeutic plasma exchange and rituximab successfully reduced the AAV Ab titers to the range of eligibility for onasemnogene abeparvovec (clinical trial result).59%40705999
motor function16/21 (76%) children gained at least one WHO motor milestone following treatment with onasemnogene abeparvovec (clinical trial result).59%35170254
safetySix (18%) had adverse events that were considered serious and related to onasemnogene abeparvovec (clinical trial result).59%34536405
drug targetNusinersen, onasemnogene abeparvovec-xioi, and risdiplam all target upregulation of SMN protein.59%35942665
drug targetOnasemnogene abeparvovec-xioi is a treatment for SMA targeting SMN1 gene replacement.59%33003005
drug efficacyNusinersen and onasemnogene abeparvovec treatment is associated with a 30-point improvement in CHOP-INTEND score (clinical trial result)59%32515646
motor functionTreatment with onasemnogene abeparvovec has led to rapid motor function improvement, often within one month of dosing (clinical trial result).59%34980814

Off-Target Findings (0)

No Boltz-2 / Chai-1 off-target panel claims recorded for this drug.

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