Source: European Medicines Agency (EU) Revision Year: 2025 Publisher: InflaRx GmbH, Winzerlaer Strasse 2, 07745 Jena, Germany
Pharmacotherapeutic group: Immunosuppressants, complement inhibitors
ATC code: L04AJ10
Vilobelimab is a chimeric human/mouse monoclonal IgG4 antibody that is a specific inhibitor of the soluble human complement component C5a.
The reduction of C5a plasma concentrations in response to vilobelimab treatment has been evaluated in the PANAMO phase III study. In general, baseline C5a levels were elevated in these patients compared to mean values found in healthy individuals and treatment with vilobelimab reduced the mean baseline C5a levels.
The efficacy of vilobelimab has been studied in the PANAMO phase III, double-blind, randomised, placebo-controlled, multinational, multicentre trial, evaluating vilobelimab for the treatment of COVID-19 in adult (≥18 years) patients requiring invasive mechanical ventilation (IMV) (with or without extracorporeal membrane oxygenation (ECMO)). A total of 369 patients were randomised in the study: 178 patients in the VILO group and 191 patients in the Placebo group. Efficacy analyses were based on 368 patients, 177 in the vilobelimab group and 191 in the placebo group. The mean age of participation was 56 years (range: 22 to 81 years) and 68.5% were male. Common co-existing medical conditions included hypertension (46.2%), obesity (40.8%) and diabetes (29.6%) in the overall study population. Corticosteroids and antithrombotic agents were used concomitantly in 96.7% and 98.4% of patients respectively. All patients were mechanically ventilated and three patients in each arm were on ECMO. Additional demographics and baseline characteristics of patients in the PANAMO phase III trial are provided in Table 2.
Table 2. Demographics and baseline characteristics of patients in the PANAMO phase III trial:
| Vilobelimab + SoC1 (N=177) | Placebo + SoC (N=191) | |
|---|---|---|
| Age Group, n (%) | ||
| 18–39 years | 22 (12.4%) | 30 (15.7%) |
| 40–65 years | 102 (57.6%) | 103 (53.9%) |
| >65 years | 53 (29.9%) | 58 (30.4%) |
| WHO 8-point ordinal scale score2 | ||
| 6 – Intubation and mechanical ventilation | 72 (40.7%) | 59 (30.9%) |
| 7 – Ventilation + additional organ support (vasopressors, renal replacement therapy, ECMO) | 105 (59.3%) | 132 (69.1%) |
| Prior and concomitant medications | ||
| Dexamethasone or systemic corticosteroid | 176 (99.4%) | 188 (98.4%) |
| Baricitinib | 6 (3.4%) | 6 (3.1%) |
| Tocilizumab | 30 (16.9%) | 31 (16.2%) |
| Remdesivir | 10 (5.6%) | 11 (5.8%) |
SoC = standard of care.
1 A total of 369 patients were randomised in the trial (178 to vilobelimab and 191 to placebo), but one patient in the vilobelimab group was randomised in error and not included in the efficacy analyses.
2 World Health Organization 8-point ordinal scale
The primary endpoint in the study was 28-day all-cause mortality. Mortality through Day 28 in the PANAMO phase III trial are provided in Table 3.
Table 3. Mortality through Day 28 in the PANAMO phase III trial:
| Vilobelimab + SoC (N=177) | Placebo + SoC (N=191) | |
|---|---|---|
| Number of Deaths | 54 | 77 |
| Percentage with Death1 | 31.7% | 41.6% |
| Day 28 Mortality site-stratified pre-specified analysis | ||
| Hazard Ratio2 (95% CI) | 0.73 (0.50, 1.06) | |
SoC = standard of care; CI = confidence interval.
1 Results from Kaplan-Meier estimates. Percentages will not be proportional to the number of deaths divided by the total number of patients due to missing values (8 patients missing mortality status in vilobelimab + SoC and 9 in placebo + SoC).
2 Results from Cox proportional hazards regression with treatment and age as covariates.
The European Medicines Agency has deferred the obligation to submit the results of studies with Gohibic in one or more subsets of the paediatric population in treatment of COVID-19 (see section 4.2 for information on paediatric use).
This medicinal product has been authorised under ‘exceptional circumstances’. This means that due to the rarity of the disease it has not been possible to obtain complete information on this medicinal product.
The European Medicines Agency will review any new information which may become available every year and this SmPC will be updated as necessary.
The PK of vilobelimab has not been extensively studied in COVID-19 patients. In the PANAMO phase III trial (n=81 patients), mean vilobelimab plasma trough concentrations on Day 8 ranged from 21,800 to 303,000 ng/mL (147 to 2,040 nM) with a geometric mean of 138,000 ng/mL (929 nM).
Mean (s.d.) volume of distribution after a single 4 mg/kg dose to healthy volunteers was 0.0833 (0.0136) L/kg.
No data are available on the metabolism of vilobelimab in humans. Vilobelimab is a monoclonal antibody and expected to be degraded into small peptides and amino acids via non-specific catabolic pathways in the same manner as endogenous IgG.
In healthy volunteers, target mediated disposition was apparent as mean vilobelimab clearance decreased with dose from 0.06 mL/min/kg after administration of 0.02 mg/kg to 0.02 and 0.01 mL/min/kg after administration of 2 mg/kg and 4 mg/kg, respectively. Mean terminal half-life (t1/2) was found to be 101.3 hours and 94.9 hours after single vilobelimab doses of 2 mg/kg and 4 mg/kg, respectively.
The pharmacokinetics of vilobelimab in paediatric COVID-19 patients has not been studied.
The pharmacokinetics of vilobelimab in patients with renal impairment has not been formally studied. In general, due to its high molecular weight vilobelimab is not expected to undergo significant renal elimination.
The pharmacokinetics of vilobelimab in patients with hepatic impairment has not been studied. Vilobelimab is degraded by widely distributed proteolytic enzymes, not restricted to hepatic tissue, therefore changes in hepatic function are not expected to have any effect on elimination.
There were no adverse effects associated with vilobelimab in conventional repeated dose and pre- and postnatal developmental toxicity studies in Cynomolgus monkeys. Pharmacokinetic data in humans are insufficient to estimate the safety margins provided by these studies.
No specific studies were conducted to evaluate potential effects of vilobelimab on fertility. There were no adverse effects on male or female reproductive parameters or organs in monkeys treated for 13-weeks or 26-weeks, respectively.
Carcinogenesis and mutagenesis studies with vilobelimab have not been conducted.
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