Vyepti Adverse Reactions

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 3) 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). (See Table 3.)

Click on icon to see table/diagram/image

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 Precautions). 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 placebo-controlled 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 anti-eptinezumab 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.