VYEPTI Concentrate for solution for infusion Ref.[49510] Active ingredients: Eptinezumab

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered medicinal product should be clearly recorded.

Patients with cardiovascular, neurological or psychiatric diseases

Patients with a history of cardiovascular disease (e.g. hypertension, ischemic heart disease) were excluded from clinical studies (see section 5.1). No safety data are available in these patients. Limited safety data are available in patients with cardiovascular risk factors such as diabetes, circulatory diseases and hyperlipidaemia.

Patients with a history of neurological diseases or patients with psychiatric conditions that were uncontrolled and/or untreated were excluded from the clinical studies. Limited safety data are available in these patients.

Serious hypersensitivity

Serious hypersensitivity reactions, including anaphylactic reactions, have been reported and may develop within minutes of the infusion. Most hypersensitivity reactions occurred during infusion and were not serious (see section 4.8). If a serious hypersensitivity reaction occurs, administration of VYEPTI should be discontinued immediately and appropriate therapy initiated. If the hypersensitivity reaction is not serious, continuation of further treatment with VYEPTI is up to the discretion of the treating physician, taking into account the benefit-risk for the individual patient.

Excipients

VYEPTI contains sorbitol (E420). Patients with hereditary fructose intolerance (HFI) must not be given this medicinal product unless strictly necessary. A detailed history with regard to HFI symptoms has to be taken of each patient prior to being given this medicinal product.

Eptinezumab is not metabolized by cytochrome P450 enzymes. Therefore, interactions by eptinezumab with concomitant medications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are considered unlikely.

Pregnancy

There is limited data from the use of eptinezumab in pregnant women. Animal studies with eptinezumab do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). Human IgG is known to cross the placental barrier; therefore, eptinezumab may be transmitted from the mother to the developing fetus.

As a precautionary measure, it is preferable to avoid the use of VYEPTI during pregnancy.

Breast-feeding

There are no data on the presence of eptinezumab in human milk, the effects on the breastfed infant, or the effects on milk production. Human IgG is known to be excreted in breast milk during the first few days after birth, which is decreasing to low concentrations soon afterward; consequently, a risk to the breast-fed infant cannot be excluded during this short period. Afterwards, use of eptinezumab could be considered during breast-feeding only if clinically needed.

Fertility

The effect of eptinezumab on human fertility has not been evaluated. Animal studies with eptinezumab showed no impact on female and male fertility (see section 5.3).

VYEPTI has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

Over 2000 patients have been treated with VYEPTI in clinical studies, Of these, approximately 1000 patients were exposed for 48 weeks (four doses). the most common adverse reactions were nasopharyngitis and hypersensitivity. Most hypersensitivity reactions occurred during infusion and were not serious. Infusion site related adverse events occurred infrequently and in similar proportions of VYEPTI and placebo patients (<2%) with no apparent relationship to VYEPTI dose. The most frequently occurring infusion-site related adverse event was infusion site extravasation, which occurred in <1% of VYEPTI and placebo patients.

Tabulated list of adverse reactions

Adverse reactions from clinical trials and post-marketing experience (table 1) are classified by MedDRA system organ classification and frequency. Frequencies have been evaluated according to the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).

Table 1. List of Adverse Reactions:

¹ Not reported in PROMISE 1 and PROMISE 2, but reported in other studies and in the post-marketing setting.

Description of selected adverse reactions

Nasopharyngitis

Approximately 8% of patients on 300 mg, 6% of patients on 100 mg and 6% of patients on placebo in PROMISE 1 and PROMISE 2 experienced nasopharyngitis. Nasopharyngitis was most frequent after the first dose of VYEPTI at any dose. The incidence decreased notably with subsequent doses and remained fairly steady thereafter.

Hypersensitivity reactions

Serious hypersensitivity reactions, including anaphylactic reactions, have been reported and may develop within minutes of the infusion (see section 4.4). The reported anaphylactic reactions have included symptoms of hypotension and respiratory difficulties, and have led to discontinuation of VYEPTI. Other hypersensitivity reactions, including angioedema, urticaria, flushing, rash and pruritus, were reported in approximately 4% of patients on 300 mg, 3% of patients on 100 mg and 1% of patients on placebo in PROMISE 1 and PROMISE 2

Fatigue

Approximately 3% of patients on eptinezumab and 2% of patients on placebo in the placebocontrolled clinical trials experienced fatigue. Fatigue was most frequent on the day of the first infusion. Following the first week and with subsequent infusions, fatigue was reported in lower incidences and the incidences were comparable to placebo.

Immunogenicity

In the clinical studies, PROMISE 1 (up to 56 weeks) and PROMISE 2 (up to 32 weeks), the incidence of anti-eptinezumab antibodies across both studies was 18% (105/579) and 20% (115/574) in patients receiving 100 mg and 300 mg every 12 weeks, respectively. In both studies, the incidence of antieptinezumab antibodies peaked at week 24 and thereafter showed a steady decline even after subsequent dosing every 12 weeks. The incidence of neutralizing antibodies across both studies was 8.3% (48/579) and 6.1% (35/574) for the 100 mg and 300 mg treatment groups, respectively.

In an open-label study, PREVAIL (up to 96 weeks of treatment with 300 mg VYEPTI every 12 weeks), 18% (23/128) of patients developed anti-eptinezumab antibodies with an overall incidence of neutralizing antibodies of 7% (9/128). 5.3% patients were ADA positive at week 48, 4% were ADA positive at week 72, and all patients, except one patient lost to follow up, were ADA negative at week 104 (the last assessment in the study).

In the clinical studies, eptinezumab trough plasma concentrations appeared lower in patients who developed anti-eptinezumab antibodies. There was no evidence of impact of anti-eptinezumab antibody development on efficacy or safety in the clinical studies.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products, except those mentioned in section 6.6.