Onasemnogene Abeparvovec-Xioi side effects: what 2,268 FDA adverse event reports show
Drug class
Adeno-associated virus (aav) vector-based gene therapy
Brand names
Zolgensma
Who reports
2,268 reports · 63% serious · 157 with death outcome · 53% female
Used for
ZOLGENSMA is an adeno-associated virus (AAV) vector-based gene therapy indicated for the treatment of pediatric patients less than 2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene. Limitations of Use The safety and effectiveness of repeat administration of ZOLGENSMA have not been evaluated .
What it is
ZOLGENSMA is a suspension of an adeno-associated viral vector-based gene therapy for intravenous infusion. It is a recombinant self-complementary AAV9 containing a transgene encoding the human survival motor neuron (SMN) protein, under the control of a cytomegalovirus enhancer/chicken-β-actin hybrid promoter.
Boxed warning
SERIOUS LIVER INJURY and ACUTE LIVER FAILURE Cases of acute liver failure with fatal outcomes have been reported. Acute serious liver injury and elevated aminotransferases can also occur with ZOLGENSMA [see Warnings and Precautions ( 5.1 )]. Patients with preexisting liver impairment may be at higher risk [see Warnings and Precautions ( 5.1 )].
Causality screen of the 40 strongest signals
What the badges mean
- Labeled — boxed warning The term (or its clinical synonym) appears in the FDA boxed warning: causality is regulator-recognised and considered serious.
- Labeled adverse reaction The exact term appears in the label's warnings or adverse-reactions sections: a known, expected effect. The FAERS signal confirms the label rather than discovering anything.
- Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
- Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
- Lab value / disease marker A laboratory result, investigation or disease-activity marker (antibody positive, CRP abnormal, swollen joint count) not described in the label. These usually mirror the monitored disease or testing protocol rather than a drug effect; not screened further.
- Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.
Strongest disproportionality signals
Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only and flags pairs whose reports are unusually skewed by sex or come mostly from consumers rather than clinicians. 57 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Liver function test increased | 146 | 63.7 54.4–74.6ROR 68.0 · χ² 8,898 / p <1e-300 | 62.8 EB05 54.7 · IC025 +5.4 3/3 methods agree | Labeled (related wording) related wording | serious PRR 53.3 | no trial data cached |
| Aspartate aminotransferase increased | 353 | 61.9 56.2–68.1ROR 73.1 · χ² 20,992 / p <1e-300 | 61.3 EB05 56.1 · IC025 +5.6 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 53.5 | no trial data cached |
| Blood lactate dehydrogenase increased | 99 | 57.8 47.6–70.1ROR 60.3 · χ² 5,434 / p <1e-300 | 56.8 EB05 48.0 · IC025 +5.2 3/3 methods agree | Lab value / disease marker | serious PRR 55.4 | no trial data cached |
| Thrombotic microangiopathy | 50 | 48.0 36.4–63.1ROR 49.0 · χ² 2,242 / p <1e-300 | 46.9 EB05 37.0 · IC025 +4.6 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 43.7 · ♀ 74% (drug 53%) · 92% clinician | no trial data cached |
| Alanine aminotransferase increased | 315 | 47.6 43.0–52.8ROR 55.2 · χ² 14,307 / p <1e-300 | 47.3 EB05 43.1 · IC025 +5.3 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 39.6 | no trial data cached |
| Transaminases increased | 99 | 41.4 34.1–50.2ROR 43.2 · χ² 3,848 / p <1e-300 | 40.9 EB05 34.6 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | serious PRR 37.8 | no trial data cached |
| Hepatic enzyme increased | 268 | 36.6 32.7–41.0ROR 41.4 · χ² 9,238 / p <1e-300 | 36.4 EB05 32.9 · IC025 +4.9 3/3 methods agree | Labeled (related wording) related wording | serious PRR 27.6 | no trial data cached |
| Atelectasis | 37 | 35.4 25.7–48.8ROR 36.0 · χ² 1,199 / p 5e-263 | 34.7 EB05 26.3 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious PRR 32.7 | no trial data cached |
| Aspiration | 31 | 26.5 18.7–37.6ROR 26.9 · χ² 734 / p 5e-162 | 26.1 EB05 19.2 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious PRR 24.9 | no trial data cached |
| Platelet count increased | 36 | 25.5 18.5–35.3ROR 25.9 · χ² 823 / p 3e-181 | 25.2 EB05 19.0 · IC025 +3.7 3/3 methods agree | Lab value / disease marker | serious PRR 23.1 | no trial data cached |
| Body temperature increased | 51 | 23.1 17.6–30.3ROR 23.6 · χ² 1,054 / p 2e-231 | 22.9 EB05 18.1 · IC025 +3.8 3/3 methods agree | Lab value / disease marker | serious PRR 21.4 · 71% consumer | no trial data cached |
| Salivary hypersecretion | 23 | 21.3 14.2–32.0ROR 21.5 · χ² 425 / p 1e-94 | 20.9 EB05 14.6 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 24.2 | no trial data cached |
| Hypotonia | 21 | 19.4 12.7–29.7ROR 19.6 · χ² 348 / p 7e-78 | 19.0 EB05 12.9 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious PRR 17.4 | no trial data cached |
| Blood test abnormal | 28 | 18.5 12.8–26.7ROR 18.7 · χ² 445 / p 5e-99 | 18.2 EB05 13.1 · IC025 +3.2 3/3 methods agree | Reporting / coding artifact | serious PRR 25.9 · 96% consumer | no trial data cached |
| Proteinuria | 34 | 16.7 12.0–23.3ROR 16.9 · χ² 486 / p 6e-108 | 16.5 EB05 12.2 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 17.1 · 94% clinician | no trial data cached |
| Hepatic cytolysis | 22 | 16.7 11.0–25.3ROR 16.8 · χ² 308 / p 3e-69 | 16.2 EB05 11.0 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 15.2 · 95% clinician | no trial data cached |
| Secretion discharge | 22 | 16.5 10.9–25.0ROR 16.6 · χ² 304 / p 2e-68 | 16.1 EB05 10.9 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 21.4 | no trial data cached |
| Gamma-glutamyltransferase increased | 39 | 16.3 11.9–22.2ROR 16.5 · χ² 544 / p 1e-120 | 16.1 EB05 12.2 · IC025 +3.2 3/3 methods agree | Lab value / disease marker | serious PRR 14.7 | no trial data cached |
| Thrombocytopenia (low platelets) | 196 | 16.3 14.2–18.6ROR 17.7 · χ² 2,805 / p <1e-300 | 16.2 EB05 14.4 · IC025 +3.7 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 15.0 | no trial data cached |
| Tachypnoea | 23 | 15.7 10.5–23.6ROR 15.9 · χ² 302 / p 6e-68 | 15.3 EB05 10.4 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 14.8 | no trial data cached |
| Hepatomegaly | 16 | 15.0 9.2–24.5ROR 15.1 · χ² 195 / p 1e-44 | 14.2 EB05 8.6 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 14.9 | no trial data cached |
| Platelet count decreased | 168 | 14.6 12.6–16.9ROR 15.7 · χ² 2,123 / p <1e-300 | 14.5 EB05 12.8 · IC025 +3.6 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 13.1 | no trial data cached |
| Respiratory disorder | 47 | 14.5 10.9–19.3ROR 14.8 · χ² 577 / p 7e-128 | 14.3 EB05 11.1 · IC025 +3.2 3/3 methods agree | Labeled (related wording) related wording | serious PRR 15.0 | no trial data cached |
| Respiratory distress | 43 | 14.4 10.7–19.4ROR 14.7 · χ² 523 / p 4e-116 | 14.2 EB05 10.8 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious PRR 13.4 | no trial data cached |
| Neutrophil count increased | 16 | 14.4 8.8–23.5ROR 14.5 · χ² 186 / p 1e-42 | 13.5 EB05 8.2 · IC025 +2.5 3/3 methods agree | Lab value / disease marker | serious PRR 13.6 | no trial data cached |
| Pyrexia (fever) | 534 | 14.3 13.3–15.4ROR 18.4 · χ² 6,682 / p <1e-300 | 14.2 EB05 13.3 · IC025 +3.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 12.2 | no trial data cached |
| Respiratory tract infection | 38 | 13.5 9.9–18.6ROR 13.8 · χ² 429 / p 1e-95 | 13.2 EB05 9.9 · IC025 +3.0 3/3 methods agree | Labeled (related wording) related wording | serious PRR 15.2 | no trial data cached |
| Motor dysfunction | 14 | 12.8 7.6–21.6ROR 12.9 · χ² 141 / p 9e-33 | 11.5 EB05 6.6 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious PRR 12.7 | no trial data cached |
| Acute respiratory failure | 25 | 12.1 8.2–17.9ROR 12.2 · χ² 243 / p 4e-55 | 11.4 EB05 7.8 · IC025 +2.6 3/3 methods agree | Labeled (related wording) related wording | serious PRR 11.1 | no trial data cached |
| Pneumonia aspiration | 32 | 11.9 8.4–16.8ROR 12.0 · χ² 308 / p 3e-69 | 11.4 EB05 8.2 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious PRR 10.9 | no trial data cached |
| Pneumothorax | 19 | 11.1 7.1–17.4ROR 11.2 · χ² 164 / p 6e-38 | 10.1 EB05 6.4 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 10.2 | no trial data cached |
| Oxygen saturation decreased | 66 | 10.9 8.6–13.9ROR 11.2 · χ² 587 / p 5e-130 | 10.7 EB05 8.6 · IC025 +2.9 3/3 methods agree | Lab value / disease marker | serious PRR 9.5 | no trial data cached |
| Blood bilirubin increased | 32 | 10.9 7.7–15.4ROR 11.1 · χ² 279 / p 6e-63 | 10.4 EB05 7.4 · IC025 +2.7 3/3 methods agree | Lab value / disease marker | serious PRR 11.5 | no trial data cached |
| Petechiae | 12 | 10.7 6.1–18.8ROR 10.7 · χ² 96 / p 7e-23 | 8.9 EB05 5.0 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 10.8 | no trial data cached |
| Vomiting | 500 | 9.9 9.1–10.7ROR 12.4 · χ² 4,063 / p <1e-300 | 9.8 EB05 9.1 · IC025 +3.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 8.5 | no trial data cached |
| Blood creatine phosphokinase increased | 31 | 9.8 6.9–13.9ROR 9.9 · χ² 237 / p 1e-53 | 9.1 EB05 6.6 · IC025 +2.5 3/3 methods agree | Lab value / disease marker | serious PRR 9.4 | no trial data cached |
| Cyanosis (blue skin from low oxygen) | 16 | 9.4 5.8–15.3ROR 9.5 · χ² 112 / p 2e-26 | 8.1 EB05 5.0 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 9.1 | no trial data cached |
| White blood cell count increased | 39 | 9.4 6.9–12.8ROR 9.5 · χ² 284 / p 6e-64 | 8.8 EB05 6.6 · IC025 +2.5 3/3 methods agree | Lab value / disease marker | serious PRR 9.5 | no trial data cached |
| Hepatic function abnormal | 37 | 9.2 6.7–12.7ROR 9.4 · χ² 264 / p 1e-59 | 8.7 EB05 6.4 · IC025 +2.5 3/3 methods agree | Labeled (related wording) related wording | serious PRR 8.6 · 95% clinician | no trial data cached |
| Red blood cell sedimentation rate increased | 11 | 9.2 5.1–16.6ROR 9.2 · χ² 72 / p 1e-17 | 7.3 EB05 4.1 · IC025 +1.7 3/3 methods agree | Lab value / disease marker | serious PRR 9.5 | no trial data cached |
Trial evidence (ClinicalTrials.gov)
Most frequently reported reactions
By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Pyrexia (fever) | 534 | 14.3 13.3–15.4ROR 18.4 · χ² 6,682 / p <1e-300 | 14.2 EB05 13.3 · IC025 +3.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 12.2 | no trial data cached |
| Vomiting | 500 | 9.9 9.1–10.7ROR 12.4 · χ² 4,063 / p <1e-300 | 9.8 EB05 9.1 · IC025 +3.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 8.5 | no trial data cached |
| Aspartate aminotransferase increased | 353 | 61.9 56.2–68.1ROR 73.1 · χ² 20,992 / p <1e-300 | 61.3 EB05 56.1 · IC025 +5.6 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 53.5 | no trial data cached |
| Alanine aminotransferase increased | 315 | 47.6 43.0–52.8ROR 55.2 · χ² 14,307 / p <1e-300 | 47.3 EB05 43.1 · IC025 +5.3 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 39.6 | no trial data cached |
| Hepatic enzyme increased | 268 | 36.6 32.7–41.0ROR 41.4 · χ² 9,238 / p <1e-300 | 36.4 EB05 32.9 · IC025 +4.9 3/3 methods agree | Labeled (related wording) related wording | serious PRR 27.6 | no trial data cached |
| Thrombocytopenia (low platelets) | 196 | 16.3 14.2–18.6ROR 17.7 · χ² 2,805 / p <1e-300 | 16.2 EB05 14.4 · IC025 +3.7 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 15.0 | no trial data cached |
| Platelet count decreased | 168 | 14.6 12.6–16.9ROR 15.7 · χ² 2,123 / p <1e-300 | 14.5 EB05 12.8 · IC025 +3.6 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 13.1 | no trial data cached |
| Liver function test increased | 146 | 63.7 54.4–74.6ROR 68.0 · χ² 8,898 / p <1e-300 | 62.8 EB05 54.7 · IC025 +5.4 3/3 methods agree | Labeled (related wording) related wording | serious PRR 53.3 | no trial data cached |
| Transaminases increased | 99 | 41.4 34.1–50.2ROR 43.2 · χ² 3,848 / p <1e-300 | 40.9 EB05 34.6 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | serious PRR 37.8 | no trial data cached |
| Blood lactate dehydrogenase increased | 99 | 57.8 47.6–70.1ROR 60.3 · χ² 5,434 / p <1e-300 | 56.8 EB05 48.0 · IC025 +5.2 3/3 methods agree | Lab value / disease marker | serious PRR 55.4 | no trial data cached |
| Dysphagia (difficulty swallowing) | 67 | 6.5 5.2–8.3ROR 6.7 · χ² 311 / p 8e-70 | 6.3 EB05 5.1 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 6.1 | no trial data cached |
| Oxygen saturation decreased | 66 | 10.9 8.6–13.9ROR 11.2 · χ² 587 / p 5e-130 | 10.7 EB05 8.6 · IC025 +2.9 3/3 methods agree | Lab value / disease marker | serious PRR 9.5 | no trial data cached |
| Tachycardia (fast heart rate) | 57 | 5.9 4.6–7.7ROR 6.1 · χ² 230 / p 3e-52 | 5.7 EB05 4.5 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 5.8 | no trial data cached |
| Irritability | 57 | 8.8 6.8–11.3ROR 9.0 · χ² 385 / p 6e-86 | 8.4 EB05 6.6 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 7.0 | no trial data cached |
| Body temperature increased | 51 | 23.1 17.6–30.3ROR 23.6 · χ² 1,054 / p 2e-231 | 22.9 EB05 18.1 · IC025 +3.8 3/3 methods agree | Lab value / disease marker | serious PRR 21.4 · 71% consumer | no trial data cached |
Unlabeled candidate signals
These flagged terms were not found in the FDA label text and do not match an artifact pattern. They are the pairs that would merit a structured assessment (temporality, dose-response, biological plausibility, consistency across databases, trial or cohort evidence). The screen has not done that; string-matching misses label wording, and a strong PRR can still be stimulated reporting, co-medication, or the disease itself.
- Transaminases increased — n=99, PRR 41.4
- Atelectasis — n=37, PRR 35.4
- Aspiration — n=31, PRR 26.5
- Salivary hypersecretion — n=23, PRR 21.3
- Hypotonia — n=21, PRR 19.4
- Proteinuria — n=34, PRR 16.7
- Hepatic cytolysis — n=22, PRR 16.7
- Secretion discharge — n=22, PRR 16.5
- Tachypnoea — n=23, PRR 15.7
- Respiratory distress — n=43, PRR 14.4
Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.
Common questions
What are the most reported side effects of Onasemnogene Abeparvovec-Xioi?
In FDA FAERS, the most frequently co-reported reaction terms for Onasemnogene Abeparvovec-Xioi are pyrexia, vomiting, aspartate aminotransferase increased, alanine aminotransferase increased, hepatic enzyme increased, thrombocytopenia. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.
Does Onasemnogene Abeparvovec-Xioi have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: SERIOUS LIVER INJURY and ACUTE LIVER FAILURE Cases of acute liver failure with fatal outcomes have been reported. Acute serious liver injury and elevated aminotransferases can also occur with ZOLGENSMA [see Warnings and Precautions ( 5.1 )]. Patients with preexisting liver impairment may be at higher risk [see Warnings and Precautions ( 5.1 )].
Do FAERS signals prove that Onasemnogene Abeparvovec-Xioi causes these side effects?
No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.
Sources & methods
- FDA label via openFDA (set ID 68cd4f06-70e1-40d8-bedb-609ec0afa471, effective 20260616; matched on
openfda.generic_name.exact:"ONASEMNOGENE ABEPARVOVEC-XIOI") - Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
- FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA
count=aggregation, fieldpatient.drug.openfda.generic_name.exact, 97 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction - Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
- Seriousness and sex counts from openFDA
count=serious,patient.patientsex,seriousnessdeath
Page generated 2026-10-08. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.