Adverse event profile of ibalizumab based on Phase I through Phase III clinical trial data and real-world use experience.
| Category | Event/finding | Notes and clinical context |
|---|---|---|
| Common TEAEs (mild-to-moderate) | Diarrhoea (24%), headache (22%), nausea (16%), cough (16%), rash (16%), fatigue (6%) | All were mild to moderate in severity. Discontinuation attributable to adverse effects was rare. |
| Serious adverse events (SAEs) | Immune reconstitution inflammatory syndrome (IRIS), pyrexia, septic shock, altered mental status, pulmonary hypertension, progressive multifocal leukoencephalopathy, cytomegalovirus viraemia | Most SAEs reflect complications of advanced immunodeficiency rather than direct drug toxicity; direct causal attribution to ibalizumab not established. |
| Resistance | Loss of N-linked glycosylation in the V5 loop of gp120 | Emerges rapidly (1–2 weeks) with monotherapy; also documented after a single missed infusion at 2,000 mg every-4-week dosing; substantially mitigated by concurrent optimised background regimen (OBR). |
| Immunological safety | No MHC class II interference; no direct CD4-mediated immune impairment | Mechanistically superior to domain 1-targeting CD4 antibodies; preserves physiological T-helper cell function. |
| Infusion-related events | Injection-site and infusion-related reactions | Infrequent, generally self-limiting; relevant to intravenous route of administration. |
| Pregnancy (animal data) | Reversible neonatal lymphopenia in cynomolgus monkeys [enhanced pre- and postnatal development (ePPND) study]; no structural teratogenicity identified | No human reproductive data; manufacturer-mandated pregnancy registry active; effective contraception recommended during treatment. |
| Breastfeeding | Expected low transfer to breast milk (MW ~150,000 Da); probable significant GI degradation in nursing infant | Caution advised, particularly for neonates and preterm infants; human lactation data absent. |