VONVENDI SIDE EFFECTS
- Generic Name: von willebrand factor (recombinant) for injection
- Brand Name: Vonvendi
SIDE EFFECTS
The most common adverse reactions observed in ≥2% of subjects in clinical trials with VONVENDI (n=80) were generalized pruritus, nausea and dizziness.
One subject treated with VONVENDI in the surgery study for perioperative management of bleeding developed proximal deep vein thrombosis postoperatively.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety profile of VONVENDI was evaluated in four prospective, multicenter trials; three were conducted in subjects with VWD (n=80) and one was conducted in subjects with hemophilia A (n=12). The ADR terms listed below (Table 1) were assessed by the sponsor/company as having a plausible causal relationship to the study medication. The adverse reactions taken into consideration were those reported in the three VWD trials.
Table 1. Summary of Adverse Reactions in Patients with von Willebrand Diseasea
| System Organ Class (SOC) | Adverse Reaction | Number of Subjects (%)b (n=80) |
Number of Infusions (%)c (n=476) |
| Cardiac Disorders | Tachycardia | 1 (1.25%) | 1 (0.21%) |
| Gastrointestinal Disorders | Nausea | 3 (3.75%) | 3 (0.63%) |
| General Disorders and Administration Site Conditions | Infusion site paresthesia | 1 (1.25%) | 1 (0.21%) |
| Chest discomfort | 1 (1.25%) | 1 (0.21%) | |
| Skin and Subcutaneous Tissues Disorders | Generalized pruritus | 2 (2.50%) | 2 (0.42%) |
| Vascular Disorder | Hot flush | 1 (1.25%) | 1 (0.21%) |
| Hypertension | 1 (1.25%) | 2 (0.42%) | |
| Deep vein thrombosis | 1 (1.25%) | 2 (0.42%) | |
| Nervous System Disorders | Dizziness | 3 (3.75%) | 3 (0.63%) |
| Dysgeusia | 1 (1.25%) | 1 (0.21%) | |
| Tremor | 1 (1.25%) | 1 (0.21%) | |
| Investigations | Heart rate increase | 1 (1.25%) | 1 (0.21%) |
| Electrocardiogram T wave inversions |
1 (1.25%) | 1 (0.21%) | |
| a This trial was done using ADVATE [Antihemophilic factor (recombinant)], a recombinant factor VIII. b Percentages by subject were calculated using the number of all subjects who had the listed adverse events, including ALL AEs that are related c Total number of unique infusions after which at least one AE was reported of the respective ADR preferred term divided by total number of infusions (N) and multiplied by 100. |
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Immunogenicity
The immunogenicity of VONVENDI was assessed in clinical trials by assessing the development of neutralizing antibodies against VWF and FVIII, as well as binding antibodies against VWF, Furin, Chinese hamster ovary (CHO) protein and mouse IgG. Neutralizing antibodies against either VWF or factor VIII were not observed. One out of 80 subjects who received VONVENDI in the clinical trials developed treatment-emergent binding antibodies against VWF. No binding antibodies against potential impurities such as rFurin, CHO-protein or mouse IgG developed after treatment with VONVENDI.
Two subjects included in Phase 1 study had pre-existing high-titer specific binding antibodies against VWF. The high titer binding anti-VWF antibodies were associated with a significantly decreased VWF:Ag activity post infusion of either plasma derived VWF (pdVWF) or rVWF and consequently, the decreased activity of VWF:RCo, VWF:CB and FVIII:C. This finding indicates the potential clinical significance of pre-existing binding (non-neutralizing) antibodies: VWD patients previously treated with pdVWF concentrates may be at risk to express a pre-existing binding antibody against VWF prior to first exposure to rVWF which could potentially result in a decreased hemostatic response to rVWF. Such patients could be managed clinically by administration of higher doses of rVWF based on the PK data for each individual patient.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, it may be misleading to compare the incidence of antibodies to VONVENDI in the studies described above with the incidence of antibodies in other studies or to other products.
SRC: NLM .