Vyepti

The concentrate for solution for infusion is clear to slightly opalescent, colourless to brownish-yellow.
Each vial contains 100 mg/mL eptinezumab.
Eptinezumab is a humanised monoclonal immunoglobulin G1 (IgG1) antibody.
Excipients/Inactive Ingredients: Sorbitol, L-histidine, L-histidine hydrochloride monohydrate, Polysorbate 80, Water for Injection.

Pharmacotherapeutic group: Analgesics, calcitonin gene-related peptide (CGRP) antagonists. ATC code: N02CD05.
Pharmacology: Pharmacodynamics: Mechanism of action: Eptinezumab is a humanized immunoglobulin G1 (IgG1) antibody that binds to α- and β-forms of human calcitonin gene-related peptide (CGRP) ligand with low picomolar affinity (4 and 3 pM K_D, respectively). This, in combination with the 100% bioavailability following an IV administration, translates into fast blockage of the biological effects of circulating CGRP in humans. As a result, eptinezumab prevents the activation of the CGRP receptors and hence the downstream cascade of physiological events linked to initiation, frequency and severity of migraine attacks.
Eptinezumab is highly selective and does not bind to any of the related neuropeptides amylin, calcitonin, adrenomedullin and intermedin.
Pharmacodynamic effects: Pharmacodynamic activity characterized by inhibition of α-CGRP-mediated neurogenic vasodilation induced by topical capsaicin relative to baseline was evaluated following single or multiple administrations of eptinezumab in human volunteers. Mean neurogenic induced vasodilation was reduced by 41% following intravenous 100 mg eptinezumab administration compared to an increase of 12% for placebo on the day following treatment. For up to 12 weeks, the reduction persisted ranging from 20% to 50% for 100 mg eptinezumab while placebo ranged from a 20% increase to 0.20% reduction during the same period.
Clinical efficacy and safety: VYEPTI was evaluated for the preventive treatment of migraine in two pivotal placebo-controlled studies: PROMISE 1 was conducted in patients with episodic migraine (n=888) and PROMISE 2 in patients with chronic migraine (n=1072). Enrolled patients had a history of migraine (with or without aura) of at least 12 months, according to the International Classification of Headache Disorders (ICHD-II or III) diagnostic criteria.
The long-term safety of VYEPTI following repeated dosing for up to 2 years was further evaluated in patients with chronic migraine in an open-label study, PREVAIL, (n=128).
The efficacy of VYEPTI was also evaluated during a migraine attack occurring in patients who were candidates for preventive treatment of migraine: RELIEF was conducted in patients with migraine as defined by ICHD-3 with ≥4 and ≤15 migraine days per month in the 3 months prior to screening (n=480).
PROMISE 1: Episodic Migraine: PROMISE 1 was a parallel group, double-blind, placebo-controlled global study to evaluate the efficacy and safety of VYEPTI for the preventive treatment of episodic migraine (defined as ≤14 headache days of which at least 4 migraine days during the past 3 months and confirmed during the 28-day screening period) in adults. 665 patients were randomized to placebo (N=222), 100 mg eptinezumab (N=221), or 300 mg eptinezumab (N=222) every 12 weeks for 48 weeks (4 infusions). Patients were allowed concurrent acute migraine or headache medications, including migraine-specific medications (i.e., triptans, ergotamine derivatives), during the study. Regular use (greater than 7 days per month) of other treatments for the prevention of migraine was not allowed.
The primary efficacy endpoint was the change from baseline in mean monthly migraine days (MMD) over Weeks 1-12. The key secondary endpoints included ≥50% and ≥75% migraine responder rates defined as the proportion of patients achieving at least the specified percent reduction in migraine days over Weeks 1-12, ≥75% migraine responder rate over Weeks 1-4, and the percentage of patients with a migraine on the day after the first dosing (Day 1).
Patients had a mean age of 40 years (range: 18 to 71 years), 84% were women, and 84% were white. The mean number of migraine days per month at baseline was 8.6 and the rate of patients with a migraine on a given day was 30.7% during the screening period; both were similar across treatment groups.
The 4-week results over Weeks 1-48, following four quarterly infusions of VYEPTI treatment are presented as changes from baseline in mean MMD (Figure 1). Both VYEPTI 100 mg and 300 mg treatment groups demonstrated statistically significant and clinically meaningful greater improvements from baseline to week 1-12 compared to placebo on mean MMD. For both doses of VYEPTI, a greater mean decrease in MMDs compared to placebo was observed from the first day after administration and was sustained for all timepoints through Week 48. (See Figure 1.)

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At each timepoint, an ANCOVA including treatment and prophylactic medication use as factors and baseline migraine days as a continuous covariate was used to estimate the mean change from baseline.
For both doses of VYEPTI the preventive treatment benefit over placebo was observed as early as Day 1 post-infusion in a prespecified analysis. The percentage of patients with a migraine on the day after dosing were lower for both the 300 and the 100 mg groups relative to placebo (13.9% (p=0.0159) and 14.8% (p=0.0312)), respectively compared to 22.5% on Day 1.
VYEPTI treatment demonstrated statistically significant and clinically meaningful improvements for primary and key secondary efficacy endpoints, as summarized in Table 1. (See Table 1.)

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Additional secondary efficacy endpoints in PROMISE 1 substantiated results from the key efficacy endpoints. In line with the ≥50% and ≥75% migraine responder rates, 100% migraine responder rates (average of 4-week means across Weeks 1-12) were higher for both doses of VYEPTI compared to placebo (100 mg and 300 mg: 11.4% and 16.8% vs placebo: 9.1%).
PROMISE 2: Chronic Migraine: PROMISE 2 was a parallel group, double-blind, placebo-controlled global study to evaluate the efficacy and safety of VYEPTI for the preventive treatment of chronic migraine (defined as ≥15 headache days, of which ≥8 were assessed as migraine days in the 3 months prior to screening and confirmed during the 28-day screening period) in adults. A total of 1,072 patients were randomized and received placebo (N=366), 100 mg eptinezumab (N=356), or 300 mg eptinezumab (N=350) every 12 weeks for 24 weeks (2 infusions). During the study, patients were allowed acute or preventive medication for migraine or headache on an established stable regimen (except for onabotulinumtoxinA). A total of 431 patients (40%) with a dual diagnosis of chronic migraine and medication overuse headache (associated with the overuse of triptans, ergotamine, or combination analgesics >10 days/month, or acetaminophen, acetylsalicylic acid, or non-steroidal anti-inflammatory drugs ≥15 days/month) confirmed during the 28 days screening period were included in the study population. Patients taking opioids or butalbital containing products >4 days/month were excluded.
The primary efficacy endpoint was the change from baseline in mean MMD over Weeks 1-12. The key secondary endpoints included ≥50% and ≥75% migraine responder rates defined as the proportion of patients achieving the specified percent reduction in migraine days over Weeks 1-12, ≥75% migraine responder rate over Weeks 1-4, the percentage of patients with a migraine on the day after dosing, the reduction in migraine prevalence from baseline to Week 4, the change from baseline in the total score on the Headache Impact Test (HIT-6) at Week 12 (300 mg dose only), and the change from baseline in acute monthly migraine medication days, mean over Weeks 1-12 (300 mg dose only). The HIT-6 is a self-administered questionnaire assessing the impact of headache on the functional status of patients with migraine. Interpretation of the impact of migraine on daily function by total score is as follows: 60-78 = Severe; 56-59 = Substantial, 50-55 = Some, and 36-49 = little to none. A clinically meaningful change (i.e response) is defined as a within person decrease from baseline of at least 5 points.
A health-related quality of life secondary endpoint was the Short-Form Health Survey Version 2 (SF-36v2). The SF-36v2 measures functional health and well-being from the patient's point of view. It comprises 36 questions which cover eight domains of health measuring quality of life over the past 4 weeks. The eight sections measured are vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. A clinically meaningful change (i.e. response) is defined as an increase of at least 3 points from baseline.
Patients had a mean age of 41 years (range: 18 to 65 years), 88% were women, and 91% were white. Forty-one percent of patients were taking concomitant preventive medication for migraine. The mean number of migraine days per month at baseline was 16.1 and the rate of patients with a migraine on a given day was 57.6% during the screening period; both were similar across treatment groups.
The monthly results over Weeks 1-24, following repeated VYEPTI infusions every 12 weeks are presented as changes from baseline in mean MMD (Figure 2). Both VYEPTI 100 mg and 300 mg treatment groups demonstrated statistically significant and clinically meaningful greater improvements from baseline to week 1-12 compared to placebo on mean MMD. For both doses of VYEPTI, a greater mean decrease in MMDs compared to placebo was observed from the first day after administration and was sustained for all timepoints through Week 24. (See Figure 2.)

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At each timepoint, an ANCOVA including treatment as a factor and baseline migraine days as a continuous covariate was used to estimate the mean change from baseline.
A preventive treatment benefit over placebo for both doses of VYEPTI was observed as early as Day 1 post-infusion in a prespecified analysis. There was a statistically significant lower frequency in day 1 migraine for both the 300 and 100 mg groups compared to placebo (27.8% [p< 0.0001] and 28.6% [p<0.0001]), respectively, compared to 42.3%, on Day 1.
Eptinezumab treatment demonstrated statistically significant and clinically meaningful improvements for key efficacy endpoints as summarized in Table 2. (See Table 2.)

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Additional secondary efficacy endpoints in PROMISE 2 substantiated results from the key efficacy endpoints. In line with the ≥50% and ≥75% migraine responder rates, 100% migraine responder rates (average of 4-week means across Weeks 1-12) were higher for both doses of VYEPTI compared to placebo (100 mg and 300 mg: 10.8% [0.8; 9.1] and 15.1% [6.2; 15.5] vs placebo: 5.1%).
In the 431 (40%) patients from PROMISE 2 diagnosed with medication overuse headache, the difference in the reduction of mean monthly migraine headache days observed between VYEPTI and placebo was -3.0 days and -3.2 for 100 mg and 300 mg, respectively.
RELIEF: Initiation of preventive treatment during a migraine attack: RELIEF was a randomized, parallel group, double-blind, placebo-controlled study to evaluate the efficacy of VYEPTI when initiated during a migraine attack occurring in patients who were candidates for preventive treatment of migraine as defined by ICHD-3 with ≥4 and ≤15 migraine days per month in the 3 months prior to screening. A total of 480 patients were randomized to receive a single infusion of either VYEPTI 100 mg or placebo in a 1:1 ratio. Treatment was initiated within 1 to 6 hours on the onset of a qualifying migraine attack.
During the study, patients were allowed rescue medication, defined as any medication to treat migraine or migraine associated symptoms, any time after 2 hours post-start of VYEPTI infusion. During the study, patients were allowed to use preventive medication for migraine or headache on an established stable regimen. Other anti-CGRP treatments were prohibited during the study.
The co-primary endpoints were time to headache pain freedom and time to absence of most bothersome symptom (selected among nausea, photophobia and phonophobia). The key secondary endpoints included headache pain freedom at 2 hours after the start of infusion and absence of most bothersome symptom at 2 hours after the start of infusion.
Patients had a mean age of 44 years (range: 18 to 75 years), 84% were women, and 86% were white. 16.4% of patients were taking concomitant preventive medication for migraine.
VYEPTI treatment demonstrated statistically significant and clinically meaningful improvements for primary and key secondary efficacy endpoints, as summarized in Table 3. (See Table 3.)

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The safety profile observed in RELIEF is consistent with the safety profile observed in the two pivotal placebo-controlled studies with VYEPTI (PROMISE 1 and 2).
PREVAIL: Long-term study: VYEPTI 300 mg was administered every 12 weeks by IV infusion in patients with chronic migraine in an open-label study for up to 2 years, with the primary objective of further evaluating the long-term safety following repeated doses of VYEPTI. Secondary objectives included characterization of the PK and immunogenicity profiles for VYEPTI (Adverse Reactions) and evaluation of the therapeutic effect of VYEPTI on several patient reported outcomes relating to quality of life and headache impact including the Headache Impact Test (HIT-6). Patients had a mean age of 41.5 years (range: 18 to 65 years), 85% were women, and 95% were white. Thirty-six percent of patients were taking concomitant preventive medication for migraine. The mean number of migraine days per 28-day period in the 3 months preceding screening was 14.1 days. There were 128 enrolled and treated patients in this study. In total, 100 patients (78.1%) completed the study (Week 104). Overall, the results of this open-label clinical study demonstrated that VYEPTI 300 mg administered by IV infusions every 12 weeks for the preventive treatment of migraine was associated with a sustained and clinically meaningful therapeutic effect, demonstrated by reductions in headache impact, improvements in measures of health-related quality of life, and overall improvement in global impressions of change in migraine over 2 years of treatment in adults with chronic migraine. The safety profile was consistent with the safety profiles observed in randomized, placebo-controlled studies with VYEPTI.
Headache impact and health related Quality of Life: The impact of migraine headache was assessed via Headache Impact Test (HIT-6) and Short Form health survey (SF-36v2), respectively, in PROMISE-2 and PREVAIL.
In PROMISE-2, at baseline patients were severely impacted, with a mean total score of 65. At week 12, patients treated with eptinezumab showed a statistically significant improvement in the HIT-6 total score versus placebo compared to baseline. The change from baseline to week 12 in the VYEPTI treatment groups was clinically meaningful: the mean change from baseline to week 12 was -6.2 (p=0.0010) for eptinezumab 100 mg, -7.3 (p<0.0001) for 300 mg, and -4.5 for placebo. The improvements were sustained over the entire treatment period and up to the safety follow-up, 20 weeks after the last infusion administration.
In the long-term study, PREVAIL, at baseline patients were severely impacted with a mean total HIT-6 of 65. The mean change from baseline through week 104 was -9.7 (p<0.0001).
In PROMISE-2, patients treated with VYEPTI showed a significant and clinically meaningful improvement in physical (PCS) and mental (MCS) component summary scores of the SF-36v2 from baseline to Week 12 compared to placebo. The mean change from baseline to week 12 in MCS was 2.78 for 100 mg (p = 0.0009), 2.78 for 300 mg (p = 0.0010), and 0.93 for placebo. The mean change from baseline to week 12 in PCS was 3.79 for 100 mg (p= 0.07), 4.86 for 300 mg (p < 0.0001), and 3.03 for placebo.
In the long-term study, PREVAIL, patients treated with VYEPTI showed clinically meaningful improvements in the physical and mental component summary scores of the SF-36v2: the mean change from baseline in MCS (baseline 51.3) was 3 (p=0.0045), and in PCS (baseline 46.7) was 4.3 (p<0.0001).
Improvement in health-related quality of life and physical function was maintained in both studies through the entire study duration of 24 weeks and 104 weeks, respectively.
Pharmacokinetics: As eptinezumab is administered intravenously, it is 100% bioavailable. Eptinezumab exhibits linear pharmacokinetics and exposure increases proportionally with doses from 1 to 1000 mg. Steady-state is attained after the first-dose during a once every 12 weeks dosing schedule. Median time to maximum concentration (C_max) is 30 minutes (end-of-infusion), and the average terminal elimination half-life is 27 days. The mean accumulation ratios based on C_max and AUC_0-tau are 1.08 and 1.15, respectively.
Absorption: VYEPTI is administered by intravenous infusion which bypasses extravascular absorption and is 100% bioavailable. Median time to peak concentration was attained at the end of infusion (30 minutes).
Distribution: The central volume of distribution (Vc) for eptinezumab was approximately 3.7 liters.
Biotransformation: Eptinezumab is expected to be degraded by proteolytic enzymes into small peptides and amino acids.
Elimination: Eptinezumab apparent clearance was 0.15 L/day, and the terminal elimination half-life was approximately 27 days.
Special populations: The pharmacokinetics of eptinezumab were not affected by age, gender, or race based on population pharmacokinetics. Therefore, no dose adjustment is needed.
A population pharmacokinetic analysis including 2123 subjects explored the effect of age, gender, ethnicity and body weight on the pharmacokinetics of eptinezumab. Relative to a 70 kg subject, steady state exposure of eptinezumab in a 190 kg subject was up to 52% lower, whereas is would be up to 50% higher in a 39 kg subject. However, from the exposure-response evaluation, there was no effect of body weight on the clinical outcome. No dose adjustment is needed based on body weight.
Renal or Hepatic Impairment: No dedicated hepatic or renal impairment studies were conducted to assess the effects of hepatic and renal impairment upon the pharmacokinetics of eptinezumab. Population pharmacokinetic analysis of integrated data from the VYEPTI clinical studies did not reveal any differences in patients with renal or hepatic impairment that would require dose adjustment.
Toxicology: Preclinical safety data: Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated-dose toxicity, juvenile toxicity, or toxicity to reproduction and development.
Safety pharmacology and general toxicology: Safety pharmacology and general toxicity assessments after intravenous (IV) administration of eptinezumab once every 2 weeks for 6 months in cynomolgus monkeys identified the no-observed-adverse-effect-level (NOAEL) as the highest dose tested (150 mg/kg/dose). This supports a 103-fold or 123-fold safety margin, respectively, by Cmax or AUC for the highest dose (300 mg) administered by IV infusion every 12 weeks in humans.
Genotoxicity and Carcinogenesis: As eptinezumab is unlikely to interact directly with DNA or other chromosomal material, evaluations for potential genotoxicity were considered unnecessary and not performed.
As no carcinogenicity risk has been identified by extensive evaluation of the literature related to inhibition of CGRP and as no eptinezumab-related proliferative findings were observed in long term studies in monkeys, carcinogenicity testing was considered unnecessary and not performed.
Reproductive and Developmental Toxicology: Eptinezumab administered by weekly IV at doses of 0, 75 or 150 mg/kg/dose showed no adverse effects on male or female fertility (rats), embryofetal development (rats and rabbits), postnatal survival, growth, or development during the pre- and postweaning period, including behavioral or reproductive performance (rats).
For all studies, the NOAEL was the highest dose tested (150 mg/kg) which is 35-fold higher than the highest recommended human dose, based on body weight.

VYEPTI is indicated for the preventive treatment of migraine in adults who have at least 4 migraine days per month.

As for other infusion treatments, VYEPTI treatment should be initiated and supervised by a healthcare professional.
Posology: The recommended dose is 100 mg administered by intravenous infusion every 12 weeks. Some patients may benefit from a dosage of 300 mg administered by intravenous infusion every 12 weeks (see Pharmacology: Pharmacodynamics under Actions).
Special Populations: Elderly (aged 65 years and over): Although patients aged up to 75 years were included in one study, the clinical study program of VYEPTI did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.
No dose adjustment is required in elderly patients as the pharmacokinetics of Vyepti are not affected by age (see Pharmacology: Pharmacokinetics under Actions).
Renal impairment/hepatic impairment: No dose adjustment is required in patients with renal impairment or hepatic impairment (see Pharmacology: Pharmacokinetics under Actions).
Paediatric population: The safety and efficacy of eptinezumab in children below the age of 18 years has not yet been established. Currently no data are available.
Method of administration: Eptinezumab is for intravenous infusion only after dilution.
For instructions on dilution of the medicinal product prior to administration, see Special precautions for disposal and other handling under Cautions for Usage.

There has been no experience of overdose with VYEPTI. Doses up to 1000 mg have been administered intravenously to humans without tolerability issues or clinically significant adverse reactions.
In the event of an overdose, the patient should be treated symptomatically, and supportive measures instituted as required.

Hypersensitivity to the active substance or to any of the excipients listed in Description.

Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Cardiovascular risk: Patients with a history of cardiovascular disease (e.g. hypertension, ischemic heart disease) were excluded from clinical studies (see Pharmacology: Pharmacodynamics under Actions). No 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 Adverse Reactions). If a serious hypersensitivity reaction occurs, administration of VYEPTI should be discontinued immediately and appropriate therapy initiated.
Effects on ability to drive and use machines: VYEPTI is expected to have no or negligible influence on the ability to drive and use machines.

Pregnancy: There are 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 Pharmacology: Toxicology: Preclinical safety data under Actions). Human IgG is known to cross the placental barrier; therefore, eptinezumab may be transmitted from the mother to the developing fetus.
VYEPTI should not be used by pregnant women unless the expected benefit to the mother justifies the potential risk to the fetus.
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; therefore, eptinezumab may be transmitted from the mother to the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for VYEPTI and any potential effects on the breastfed infant.
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 Pharmacology: Toxicology: Preclinical safety data under Actions).

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.

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.
In healthy subjects, co-administration of a single dose of 300 mg eptinezumab administered as an intravenous infusion (over a period of 1 hour ± 15 min) with a single dose of 6 mg sumatriptan administered subcutaneously did not alter the pharmacokinetics of eptinezumab or sumatriptan.
Interactions with other drugs have not been studied.

Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products, except those mentioned in Special precautions for disposal and other handling as follows.
Special precautions for disposal and other handling: VYEPTI requires dilution prior to administration. The dilution should be prepared by a healthcare professional using aseptic technique to ensure the sterility of the prepared solution for infusion.
VYEPTI contains no preservative and is intended for single use only and any unused product should be disposed.
Prior to dilution, VYEPTI (concentrate in the vials) should be inspected visually; do not use if the solution contains visible particulate matter or is cloudy or discoloured (other than clear to slightly opalescent, colourless to brownish-yellow).
For both the 100 mg and the 300 mg dose, a 100 mL bag of 0.9% Sodium Chloride for Injection should be used to prepare the VYEPTI solution for infusion as described as follows. No other IV diluents or volumes may be used to prepare the VYEPTI solution for infusion.
Gently invert the VYEPTI solution for infusion to mix completely. Do not shake.
Following dilution, VYEPTI solution for infusion must be infused within 8 hours. During this time, VYEPTI solution for infusion may be stored at room temperature or refrigerated at 2 to 8°C. If stored at 2 to 8°C, allow the VYEPTI solution for infusion to warm to room temperature prior to infusion. DO NOT FREEZE.
100 mg dose: To prepare the VYEPTI solution for infusion, withdraw 1.0 mL of VYEPTI from one single-use vial using a sterile needle and syringe. Inject the 1.0 mL (100 mg) content into a 100 mL bag of 0.9% Sodium Chloride for Injection.
300 mg dose: To prepare the VYEPTI solution for infusion, withdraw 1.0 mL of VYEPTI from 3 single-use vials using a sterile needle and syringe. Inject the resulting 3.0 mL (300 mg) content into a 100 mL bag of 0.9% Sodium Chloride for Injection.
Infusion administration instructions: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if the liquid contains visible particulate matter or is cloudy or discolored.
Infuse VYEPTI 100 mg or 300 mg as prescribed, following dilution of the vial content in a 100 mL bag of 0.9% Sodium Chloride for Injection, over approximately 30 minutes. Use an intravenous infusion set with a 0.2 or 0.22 μm in-line or add-on filter. After the infusion is complete, flush the line with 20 mL of 0.9% Sodium Chloride for Injection.
Do not administer VYEPTI as a bolus injection.
No other medications should be administered through the infusion set or mixed with VYEPTI.
Any unused medicinal product or waste material should be disposed in accordance with local requirements.

Store in a refrigerator (2°C to 8°C).
Keep the vial in the outer carton in order to protect from light.
Do not freeze or shake.
Following dilution, the VYEPTI solution for infusion (VYEPTI and 0.9% Sodium Chloride for Injection) may be stored at room temperature or refrigerated at 2 to 8°C.
Shelf life: 36 months.
Following dilution, the VYEPTI solution for infusion (VYEPTI and 0.9% Sodium Chloride for Injection) must be infused within 8 hours (see Special precautions for disposal and other handling under Cautions for Usage).

Antimigraine Preparations

N02CD05 - eptinezumab ; Belongs to the class of calcitonin gene-related peptide (CGRP) antagonists preparations. Used to relieve migraine.

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