Vyepti Adverse Reactions

Summary of the safety profile: A total of over 2000 patients (more than 1,600 patient years) have been treated with VYEPTI in clinical studies. Of these, approximately 1,500 patients were exposed to 100 mg or 300 mg. Across all doses, 1872 patients were exposed for at least 24 weeks (two doses), 991 patients were exposed for 48 weeks (four doses), and 101 patients were exposed for up to two years (eight doses). In the placebo-controlled clinical studies (PROMISE 1 and PROMISE 2), 1372 patients received at least one dose of VYEPTI (including 579 patients receiving at least one dose of VYEPTI 100 mg and 574 patients receiving at least one dose of VYEPTI 300 mg), and 588 patients received placebo.
The most common adverse reactions in the placebo-controlled clinical studies (PROMISE 1 and PROMISE 2) for the preventive treatment of migraine were nasopharyngitis and hypersensitivity (see as follows). 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 in PROMISE 1 and PROMISE 2.
Tabulated list of adverse reactions: The table presented as follows is according to the MedDRA system organ classification. 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 4.)

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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 eptinezumab at any dose. The incidence decreased with subsequent doses and remained fairly steady thereafter.
Hypersensitivity and infusion related 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.
Other symptoms reported in association with eptinezumab infusion include respiratory symptoms (nasal congestion, rhinorrhea, throat irritation, cough, sneezing, dyspnea) and fatigue. Most of these events were non-serious and transient in nature.
Immunogenicity: In placebo-controlled pivotal clinical studies, PROMISE 1 and PROMISE 2, 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 dosing, 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 antibodies with neutralizing potential across both studies was 8.3% (48/579) and 6.1% (35/574) for the 100 mg and 300 mg treatment groups, respectively.
A long-term open label repeat dose study, PREVAIL, in 128 patients with chronic migraine consisted of a primary and secondary treatment phase in which up to eight IV infusions of VYEPTI 300 mg were administered over an 84-week period (one infusion every 12 weeks). Overall 119 patients completed the primary treatment phase (4 infusions, from baseline up to 48 weeks) and 101 patients completed the secondary treatment phase (8 infusions; from baseline up to 96 weeks). Anti-drug antibodies (ADA) developed in 18% (23/128) of patients with an overall incidence of antibodies with neutralizing potential 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).
There was no evidence of impact of anti-eptinezumab antibody development on efficacy or safety in the clinical studies.