VYEPTI is indicated for the preventive treatment of migraine in adults.
VYEPTI should be prescribed by healthcare professionals experienced in the diagnosis and treatment
of migraine.

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 section 5.1).
The treatment benefit should be assessed 3-6 months after initiation of the treatment. The need for
dose escalation should be assessed within 12 weeks after initiation of the treatment. The decision to
continue with treatment should be made on an individual patient basis, determined prior to each dose.
Special Populations
Elderly (aged 65 years and over)
Insufficient clinical data is available for patients aged 65 and older. Clinical studies with VYEPTI did
not include sufficient number of patients in this age group, to determine whether they respond
differently from younger patients. There is no dose adjustment recommendation available for this
population group.
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.
Effects on laboratory tests
Interference of VYEPTI with laboratory and/or diagnostic tests has not been studied.
Method of administration
Eptinezumab is for intravenous infusion only after dilution.
For instructions on dilution of the medicinal product prior to administration, see section 6.6.
The product 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.
The product contains no preservative and is intended for single use only.
Prior to dilution, the product (solution 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 below. No other IV diluents
or volume 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. To reduce
microbiological hazard, use as soon as practicable after dilution. 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 a 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 each of 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.
The treating Physician should observe or monitor patients during and after the infusion in accordance
with normal clinical practice (see Section 4.4 Special Warnings and Precautions for Use on Serious
Hypersensitivity).
Infuse 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, it is for intravenous infusion only after dilution.
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.
 

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 section 5.1). 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. Angioedema, urticaria, facial flushing, and rash, have occurred
with VYEPTI in clinical studies most hypersensitivity reactions occurred during infusion and were not
serious, but often led to discontinuation or required treatment (see section 4.8). If a serious
hypersensitivity reaction occurs, administration of VYEPTI should be discontinued immediately and
appropriate therapy initiated.
If a serious hypersensitivity reaction occurs with the infusion of VYEPTI, further treatment with
VYEPTI should be discontinued. If the hypersensitivity reaction is less severe, continuation of further
treatment with VYEPTI is up to it is the discretion of the treating physician.

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.

Pregnancy
There are limited data from the use of eptinezumab in pregnant women. In studies in rats and rabbits,
there were no effects on embryofetal development when eptinezumab was dosed throughout the period
of organogenesis at doses up to 150 mg/kg (25 times the MRHD in a 50 kg patient). Human IgG is
known to cross the placental barrier; therefore, eptinezumab may be transmitted from the mother to the
developing foetus.
VYEPTI should not be used by pregnant women unless the expected benefit to the mother justifies the
potential risk to the foetus.
Breastfeeding
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. There were no adverse effects on
female or male fertility in rats treated with dose levels up to 150mg/kg IV weekly (25 times the
MRHD in a 50kg patient) prior to and during mating, continuing in females to the time of
implantation.

VYEPTI is expected to have no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

A total of over 2000 patients (more than 1,600 patient years) have been treated with eptinezumab 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 placebocontrolled

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. Approximately

86% were female, 89% were white, and the mean age was 40.4 years at study entry.

Patients with a history of cardiovascular disease, neurological disease, cerebrovascular disease, morbid

obesity and diabetes were excluded from clinical studies.

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

below). Most hypersensitivity reactions occurred during infusion and were not serious (see section

4.4).

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 below 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).

Table 1: List of Adverse Reactions in Clinical Studies and Post-marketing reports

(PROMISE 1 and PROMISE 2)

System Organ Class             Adverse Reaction Preferred Term                    Frequency Category

Infections and Infestations       Nasopharyngitis                                                         Common

Immune system disorders        Hypersensitivity reactions                                         Common

                                                        Anaphylactic reaction1 Rare

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 nasopharyn-gitits. 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 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.
Immunogenicity
In placebo-controlled pivotal clinical studies, PROMISE 1 and PROMISE 2, the incidence of antieptinezumab
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
any of 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 Pharmacovigilance
and Drug Safety Center (NPC).

- To Report any side effect(s):
 Saudi Arabia:
- The National Pharmacovigilance Center (NPC)
o SFDA Call Center: 19999
o E-mail: npc.drug@sfda.gov.sa
o Website: https://ade.sfda.gov.sa/

 Other GCC states:
- Please contact the relevant competent authority.

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.
 

Pharmacotherapeutic group: Not yet assigned.
ATC code: N02CD05
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 preventing its
activation of the CGRP receptors. Elevated blood concentrations of CGRP have been associated with
migraine.
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). In PROMISE 1 episodic migraine was defined as ≥4 and ≤14
headache days of which at least 4 had to be migraine days in each 28-day period in the 3 months prior
to screening. In PROMISE 2 chronic migraine was defined as ≥ 15 to ≤ 26 headache days, of which ≥
8 were assessed as migraine days. VYEPTI was administered by intravenous infusion every 12 weeks
in both studies. 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. Patients over 75 years and patients with a history of cardiovascular disease,
neurological disease, cerebrovascular disease, and diabetes were excluded.

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 in adults. A total of
665 patients were randomized and received 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 to use
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 subjects 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 female, 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 sustained for all timepoints through to Week 48.

Figure 1 Mean Changes from Baseline in Mean Monthly Migraine Days over Time in
PROMISE 1 – Weeks 1-48

The daily results over the first week after the initial infusion of VYEPTI treatment are presented as
percentages of subjects with a migraine (Figure 2). For both doses of VYEPTI the preventive
treatment benefit over placebo was observed as early as Day 1 post-infusion.

Figure 2: Percentages of Subjects with a Migraine from Day -1 (Day Prior to Infusion) to
Day 7 in PROMISE 1 – Days 1-7

VYEPTI treatment demonstrated statistically significant and clinically meaningful improvements for
primary and key secondary efficacy endpoints, as summarized in Table 2.

Table 2: Primary and Key Secondary Efficacy Endpoint Results in PROMISE 1 (Episodic
Migraine)

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 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 to use acute or preventive medication for migraine or headache on an established stable
regimen (except for onabotulinumtoxinA). Patients 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 antiinflammatory
drugs ≥ 15 days/month) 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 subjects 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.
Patients had a mean age of 41 years (range: 18 to 65 years), 88% were female, 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 two quarterly infusions of VYEPTI treatment are
presented as changes from baseline in mean MMD (Figure 3). 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 sustained for all timepoints through to Week 24.

Eptinezumab treatment demonstrated statistically significant and clinically meaningful improvements
for key efficacy endpoints as summarized in Table 3.

a A baseline was the average over the 28-day screening period prior to receiving treatment
b Migraine prevalence: The average percent of subjects with a migraine on any given day during
baseline and the equivalent average rates over weeks 1, 2, 3, and 4
c The endpoint for the 100 mg dose was not a pre-specified key secondary endpoint.
Subjects with medication overuse headache (MOH), other than those taking opioids or butalbital > 4
days/month, were enrolled in PROMISE 2: at baseline, 40.2% of the patients had MOH. In subjects
with chronic migraine, similar reductions in MMD (Mean for Weeks 1-12) were observed in subjects
with and without MOH at baseline. The mean change from baseline in MMD (Weeks 1-12) for the
subjects with MOH was for 300 mg: -8.6, 100 mg: -8.4, placebo: -5.4 and for subjects without MOH
was 300 mg: -8.1, 100 mg: -7.4, placebo: -6.1. The mean difference to placebo in change from
baseline in MMD (Weeks 1-12) for the subjects with MOH was (300 mg: -3.2 [95% CI: -4.75; -1.70],
100 mg: -3.0 [-4.52; -1.49]) and for subjects without MOH was (300 mg: -2.4 [-3.59; -1.12], 100 mg: -
1.5 [-2.70; -0.31]).
In the 431 (40%) patients from PROMISE 2 diagnosed with medication overuse headache, the
difference in the reduction of mean monthly migraine headache days (MMD) observed between
VYEPTI® and placebo was -3.0 [95% CI: -4.52; -1.49] days and 3.2 [95% CI: 4.75; -1.70] for 100
mg and 300 mg, respectively.
PREVAIL: Long-term study
VYEPTI 300 mg was administered every 12 weeks by IV infusion for up to 96 weeks in 128 subjects
with chronic migraine. The primary objective was to evaluate the long-term safety following repeated
doses of VYEPTI. Secondary objectives included characterization of the PK and immunogenicity
profiles for VYEPTI (section 4.8) and evaluation of the therapeutic effect of VYEPTI on several
patient reported outcomes relating to migraine and quality of life including the Headache Impact Test
(HIT-6). Subjects had a mean age of 41.5 years (range: 18 to 65 years), 85% were female, and 95%
were white and 36% took 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.
In total, 100 patients (78.1%) completed the study (Week 104). The safety profile was consistent with
the safety profiles observed in randomized, placebo-controlled studies and a sustained effect on
patient-relevant outcomes was observed for up to 96 weeks.
 

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 (Cmax) is 30 minutes (end-of-infusion), and the
average terminal elimination half-life is 27 days. The mean accumulation ratios based on Cmax and
AUC0-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 based on either age, sex or race.
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.
 

Genotoxicity and Carcinogenesis
The genotoxic potential of eptinezumab has not been evaluated; however, monoclonal antibodies are
not expected to alter DNA or chromosomes.Carcinogenicity studies have not been conducted with
eptinezumab, as eptinezumab is a monoclonal antibody.

Sorbitol
L-histidine
L-histidine hydrochloride monohydrate
Polysorbate 80
Water for injection

 

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products.
No other medications should be administered through the infusion set or mixed with VYEPTI, see
Section 4.2 Dose and method of administration.

Store in a refrigerator (2 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.

 

Type I glass vial with chlorobutyl rubber stopper. The vial stopper is not made with natural rubber
latex.
Each Carton contains one vial.

N.A