EMGALITY 120mg 120mg / ml solution for injection in pre-filled pen medication leaflet

Emgality 120 mg solution for injection in pre-filled pen

Each pre-filled pen contains 120 mg of galcanezumab in 1 mL.

Galcanezumab is a recombinant humanised monoclonal antibody produced in Chinese Hamster Ovarycells.

For the full list of excipients, see section 6.1.

Solution for injection (injection).

The solution is clear and colourless to slightly yellow.

Emgality is indicated for the prophylaxis of migraine in adults who have at least 4 migraine days permonth.

Treatment should be initiated by physicians experienced in the diagnosis and treatment of migraine.

The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a240 mg loading dose as the initial dose.

Patients should be instructed to inject a missed dose as soon as possible and then resume monthlydosing.

The treatment benefit should be assessed within 3 months after initiation of treatment. Any furtherdecision to continue treatment should be taken on an individual patient basis. Evaluation of the need tocontinue treatment is recommended regularly thereafter.

There is limited information in subjects aged ≥ 65 years. No dose adjustment is required as thepharmacokinetics of galcanezumab are not affected by age.

Renal impairment/hepatic impairment

No dose adjustment is required in patients with mild to moderate renal impairment or hepaticimpairment (see section 5.2).

The safety and efficacy of galcanezumab in children aged 6 to 18 years have not yet been established.

No data are available.

There is no relevant use of galcanezumab in children below the age of 6 years for the prevention ofmigraine.

Subcutaneous use.

A patient may self-inject galcanezumab by following the Instructions for Use. Galcanezumab is to beinjected subcutaneously in the abdomen, thigh, back of the upper arm, or in the gluteal region. Aftertraining, patients may self-inject galcanezumab if a healthcare professional determines that it isappropriate. Comprehensive instructions for administration are given in the Package Leaflet.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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

Patients with certain major cardiovascular diseases were excluded from clinical studies (seesection 5.1). No safety data are available in these patients.

Serious hypersensitivity

Serious hypersensitivity reactions including cases of anaphylaxis, angioedema and urticaria have beenreported (see section 4.8). Serious hypersensitivity reactions may occur within 1 day aftergalcanezumab administration, however cases with a delayed onset (ranging from more than 1 day to4 weeks after administration) have been reported. In some cases, hypersensitivity reactions had aprolonged duration. If a serious hypersensitivity reaction occurs, administration of galcanezumabshould be discontinued immediately and appropriate therapy initiated (see section 4.3). Patients shouldbe informed on the possibility of a delayed onset hypersensitivity reaction and instructed to contacttheir physician.

This medicine contains less than 1 mmol sodium (23 mg) per 120 mg dose, that is to say essentially“sodium-free”.

No drug interaction studies were conducted. No pharmacokinetic drug interactions are expected basedon the characteristics of galcanezumab.

There are limited data from the use of galcanezumab in pregnant women. Animal studies do notindicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

Human immunoglobulin (IgG) is known to cross the placental barrier. As a precautionary measure, itis preferable to avoid the use of galcanezumab during pregnancy.

It is unknown whether galcanezumab is excreted in human milk. Human IgG is known to be excretedin breast milk during the first days after birth, which is decreasing to low concentrations soonafterwards; consequently, a risk to breast-fed infants cannot be excluded during this short period.

Afterwards, use of galcanezumab could be considered during breast-feeding only if clinically needed.

The effect of galcanezumab on human fertility has not been evaluated. Fertility studies in animals donot indicate harmful effects with respect to male and female fertility (see section 5.3).

Galcanezumab may have a minor influence on the ability to drive and use machines. Vertigo mayoccur following the administration of galcanezumab (see section 4.8).

Over 2 500 patients were exposed to galcanezumab in migraine prophylaxis studies supporting theinitial registration of galcanezumab. Over 1 400 patients were exposed to galcanezumab during thedouble-blind treatment phase of the placebo-controlled phase 3 studies. 279 patients were exposed for12 months.

The reported adverse drug reactions for 120 mg and 240 mg in the migraine clinical trials were injectionsite pain (10.1 %/11.6 %), injection site reactions (9.9 %/14.5 %), vertigo (0.7 %/1.2 %), constipation(1.0 %/1.5 %), pruritus (0.7 %/1.2 %) and urticaria (0.3 %/0.1 %). Most of the reactions were mild ormoderate in severity. Less than 2.5 % of patients in these studies discontinued due to adverse reactions.

Table 1. List of adverse reactions in clinical studies and post-marketing reports

Frequency estimate: 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).

System organ class Very common Common Uncommon Rare

Immune system Anaphylaxisdisorders Angioedema

Ear and labyrinth Vertigodisorders

Gastrointestinal Constipationdisorders

Skin and Pruritus Urticariasubcutaneous Rashtissue disorders

General disorders Injection siteand administration painsite conditions Injection sitereactionsaa Most frequently reported terms (≥ 1 %) were: Injection site reaction, Injection site erythema,

Injection site pruritus, Injection site bruising, Injection site swelling.

Injection site pain or reactions

The majority of reactions related to the injection site were mild to moderate and less than 0.5 % ofpatients exposed to galcanezumab during the phase 3 studies discontinued the treatment due to aninjection site reaction. The majority of injection site reactions were reported within 1 day and onaverage resolved within 5 days. In 86 % of the patients reporting injection site pain, the reactionoccurred within 1 hour of injection and resolved on average in 1 day. One percent of the patientsexposed to galcanezumab during the phase 3 studies experienced severe pain at the injection site.

Urticaria

While urticaria is uncommon, serious cases of urticaria have been reported in galcanezumab clinicalstudies.

In the clinical studies, the incidence of anti-drug antibody development during the double-blindtreatment phase was 4.8 % in patients receiving galcanezumab once monthly (all but one of whom hadin vitro neutralizing activity). With 12 months of treatment, up to 12.5 % of galcanezumab-treatedpatients developed anti-drug antibodies, most of which were of low titre and tested positive forneutralising activity in vitro. However, the presence of anti-drug antibodies did not affect thepharmacokinetics, efficacy, or safety of galcanezumab.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

Doses up to 600 mg have been administered subcutaneously to humans without dose-limiting toxicity.

In case of an overdose, it is recommended that the patient be monitored for any signs or symptoms ofadverse reactions and appropriate symptomatic treatment be instituted immediately.

Pharmacotherapeutic group: analgesics, calcitonin gene-related peptide (CGRP) antagonists, ATCcode: N02CD02

Galcanezumab is a humanised IgG4 monoclonal antibody that binds calcitonin gene-related peptide(CGRP) thus preventing its biological activity. Elevated blood concentrations of CGRP have beenassociated with migraine attacks. Galcanezumab binds to CGRP with high affinity (KD = 31 pM) andhigh specificity (> 10 000-fold vs related peptides adrenomedullin, amylin, calcitonin and intermedin).

The efficacy and safety of galcanezumab has been studied in 3 phase 3, randomized, placebo-controlled, double-blind studies in adult patients (N = 2 886). The 2 episodic migraine studies(EVOLVE-1 and EVOLVE-2) enrolled patients who met International Classification of Headache

Disorders (ICHD) criteria for a diagnosis of migraine with or without aura with 4-14 migraineheadache days per month. The chronic migraine study (REGAIN) enrolled patients who met ICHDcriteria for chronic migraine with ≥ 15 headache days per month, of which at least 8 had the featuresof migraine. Patients with recent acute cardiovascular events (including MI, unstable angina, CABG,stroke, DVT) and/or those deemed to be at serious cardiovascular risk were excluded from thegalcanezumab clinical trials. Patients > 65 years of age were also excluded.

Patients received placebo, galcanezumab 120 mg/month (with an initial loading dose of 240 mg for thefirst month) or galcanezumab 240 mg/month and were allowed to use medication for the acutetreatment of migraine. Across the 3 studies, patients were predominantly female (> 83 %) with a meanage of 41 years, and an average migraine history of 20 to 21 years. Approximately one-third ofpatients across the studies had at least 1 prior failure on a migraine prophylactic treatment for efficacyreasons and approximately 16 % of patients across the studies had at least 2 prior failure on aprophylactic treatment for efficacy reasons.

In all 3 studies, the overall mean change from baseline in number of monthly Migraine Headache

Days (MHDs) was the primary efficacy measure. Response rate is the mean percentage of patientsmeeting a defined threshold in the reduction of the number of monthly MHDs (≥ 50 %, ≥ 75 % and100 %) across the double-blind treatment period. The impact of migraine on functioning was assessedby the Role Function-Restrictive domain of the Migraine-Specific Quality of Life Questionnaire(MSQ) version 2.1, and by the Migraine Disability Assessment (MIDAS) Questionnaire. The MSQmeasures impact of migraine on work or daily activities, relationships with family and friends, leisuretime, productivity, concentration, energy, and tiredness. Scoring ranges from 0 to 100, with higherscores indicating less impairment , that is, patients experience fewer restrictions on the performance ofday-to-day activities. For the MIDAS, higher scores indicate more disability. The baseline scores ofthe MIDAS reflected severe migraine related disability of patients in EVOLVE-1 and EVOLVE-2(mean of 33.1) and a very severely disabled population (mean of 67.2) in REGAIN.

Episodic migraine

Studies EVOLVE-1 and EVOLVE-2 had a 6 month, double-blind, placebo-controlled treatmentperiod. Completion rate of the double-blind treatment phase for patients who received galcanezumabranged from 82.8 % to 87.7 %.

Both galcanezumab 120 mg and 240 mg treatment groups demonstrated statistically significant andclinically meaningful improvements from baseline compared to placebo on mean change in MHD (see

Table 2). Patients treated with galcanezumab had greater response rates and greater reductions in thenumber of monthly MHDs that acute medication was taken compared with placebo-treated patients.

Galcanezumab-treated patients had a greater improvement in functioning (as measured by the MSQ

Role Function-Restrictive domain score) compared with placebo-treated patients, beginning atmonth 1. More patients treated with galcanezumab achieved clinically significant levels ofimprovement in functioning (responder rate based on MSQ Role Function Restrictive domain)compared with those treated with placebo. Galcanezumab was associated with a statisticallysignificant reduction in disability over placebo.

Compared with placebo-treated patients, patients treated with galcanezumab 120 mg or 240 mg hadsignificantly greater mean decreases from baseline in the number of monthly MHDs at month 1 and atall subsequent months up to month 6 (see Figure 1). Additionally, in month 1, patients treated withgalcanezumab (loading dose of 240 mg) demonstrated significantly fewer weekly MHDs comparedwith placebo-treated patients, at week 1 and each subsequent week.

Figure 1 Reduction in monthly migraine headache days over time in studies EVOLVE-1 and

EVOLVE-2

Table 2. Efficacy and patient reported outcome measures

EVOLVE-1 - Episodic Migraine EVOLVE-2 - Episodic Migraine

Emgality Emgality

Placebo Placebo120 mg 240 mg 120 mg 240 mg

N = 210 N = 208 N = 425 N = 226 N = 220 N = 450

Efficacy Outcomesa

MHD

Baseline 9.21 9.14 9.08 9.07 9.06 9.19

Mean Change -4.73 -4.57 -2.81 -4.29 -4.18 -2.28

Treatment Difference -1.92 -1.76 -2.02 -1.90

CI95 % (-2.48, -1.37) (-2.31, -1.20) (-2.55, -1.48) (-2.44, -1.36)

P-value < .001d < .001d < .001d < .001d≥ 50 % MHD Responders

Percentage, % 62.3 60.9 38.6 59.3 56.5 36.0

P-value < .001d < .001d < .001d < .001d≥ 75 % MHD Responders

Percentage, % 38.8 38.5 19.3 33.5 34.3 17.8

P-value < .001d < .001d < .001d < .001d100 % MHD Responders

Percentage, % 15.6 14.6 6.2 11.5 13.8 5.7

P-value < .001d < .001d < .001d < .001d

MHD with Acute

Medication Use

Baseline 7.42 7.34 7.38 7.47 7.47 7.62

Mean Change -3.96 -3.76 -2.15 -3.67 -3.63 -1.85

Treatment Difference -1.81 -1.61 -1.82 -1.78

CI95 % (-2.28, -1.33) (-2.09, -1.14) (-2.29, -1.36) (-2.25, -1.31)

P-value < .001d < .001d < .001d < .001d

Patient-reported Outcome Measures

MSQ Role Function-

Restrictive Domainb

N 189 184 377 213 210 396

Baseline 51.39 48.76 52.92 52.47 51.71 51.35

Mean Change 32.43 32.09 24.69 28.47 27.04 19.65

Treatment Difference 7.74 7.40 8.82 7.39

CI95 % (5.20, 10.28) (4.83, 9.97) (6.33, 11.31) (4.88, 9.90)

P-value < .001d < .001d < .001d < .001d

MSQ Role Function

Restrictive Domain

Respondersc

N 189 184 377 213 210 396

Percentage, % 63.5 69.6 47.2 58.2 60.0 43.4

P-value < .001f < .001f < .001f < .001f

MIDAS Total Scoree

N 177 170 345 202 194 374

Baseline 32.93 36.09 31.84 30.87 32.75 34.25

Mean Change -21.16 -20.06 -14.87 -21.17 -20.24 -12.02

Treatment Difference -6.29 -5.19 -9.15 -8.22

CI95% (-9.45, -3.13) (-8.39, -1.98) (-12.61, -5.69) (-11.71, -4.72)

P-value < .001f .002f < .001f < .001f

N = number of patients; CI95 % = 95 % confidence interval.aEfficacy outcomes were evaluated across Months 1-6.bEvaluated across Months 4-6.cDefined as those with an improvement of ≥ 25 points for Episodic Migraine at Months 4-6 average.

dStatistically significant after adjustment for multiple comparisons.eEvaluated at Month 6.fNot adjusted for multiple comparisons.

In pooled data from studies EVOLVE-1 and EVOLVE-2, in patients who failed one or moreprophylactic treatments for efficacy reasons, the treatment difference for the reduction of meanmonthly MHDs observed between galcanezumab 120 mg and placebo was -2.69 days (p < 0.001) andbetween galcanezumab 240 mg and placebo -2.78 days (p < 0.001). In patients failing two or moreprophylactic treatments, the treatment difference was -2.64 days (p < 0.001) between 120 mg andplacebo and -3.04 days (p < 0.001) between 240 mg and placebo.

Chronic migraine

Study REGAIN had a 3 month, double-blind, placebo-controlled treatment period followed by a9 month open-label extension. Approximately 15 % of the patients continued concurrent treatmentwith topiramate or propranolol as allowed by the protocol for prophylaxis of migraine. Completionrate of the double-blind treatment phase for patients who received galcanezumab was 95.3 %.

Both galcanezumab 120 mg and 240 mg treatment groups demonstrated statistically significant andclinically meaningful improvements from baseline compared to placebo on mean change in MHD (see

Table 3). Patients treated with galcanezumab had greater response rates and greater reductions in thenumber of monthly MHDs that acute medication was taken compared with placebo-treated patients.

Galcanezumab-treated patients had a greater improvement in functioning (as measured by the MSQ

Role Function-Restrictive domain score) compared with placebo-treated patients, beginning atmonth 1. More patients treated with galcanezumab achieved clinically significant levels ofimprovement in functioning (responder rate based on MSQ Role Function Restrictive domain)compared with those treated with placebo. The 120 mg dose was associated with a statisticallysignificant reduction in disability over placebo.

Compared with placebo-treated patients, patients treated with galcanezumab 120 mg or 240 mg hadsignificantly greater mean decreases from baseline in the number of monthly MHDs at the first monthand at all subsequent months up to month 3 (see Figure 2). Additionally, in month 1, patients treatedwith galcanezumab (loading dose of 240 mg) demonstrated significantly fewer weekly MHDscompared with placebo-treated patients, at week 1 and each subsequent week.

Figure 2 Reduction in monthly migraine headache days over time in study REGAIN

Table 3. Efficacy and patient reported outcome measures

REGAIN - Chronic Migraine

Emgality

Placebo120 mg 240 mg

N = 273 N = 274 N = 538

Efficacy Outcomesa

MHD

Baseline 19.36 19.17 19.55

Mean Change -4.83 -4.62 -2.74

Treatment Difference -2.09 -1.88

CI95 % (-2.92, -1.26) (-2.71, -1.05)

P-value < .001c < .001c≥ 50 % MHD Responders

Percentage, % 27.6 27.5 15.4

P-value < .001c < .001c≥ 75 % MHD Responders

Percentage, % 7.0 8.8 4.5

P-value .031d < .001c100 % MHD Responders

Percentage, % 0.7 1.3 0.5

P-value > .05d > .05d

MHD with Acute Medication Use

Baseline 15.12 14.49 15.51

Mean Change -4.74 -4.25 -2.23

Treatment Difference -2.51 -2.01

CI95 % (-3.27, -1.76) (-2.77, -1.26)

P-value < .001d < .001 c

Patient-reported Outcome Measuresb

MSQ Role Function-Restrictive Domain

N 252 253 494

Baseline 39.29 38.93 38.37

Mean Change 21.81 23.05 16.76

Treatment Difference 5.06 6.29

CI95 % (2.12, 7.99) (3.03, 9.55)

P-value < .001d < .001c

MSQ Role Function Restrictive Domain

Responders

N 252 253 494

Percentage, % 64.3 64.8 54.1

P-value .003e .002e

MIDAS Total Score

N 254 258 504

Baseline 62.46 69.17 68.66

Mean Change -20.27 -17.02 -11.53

Treatment Difference -8.74 -5.49

CI95 % (-16.39, -1.08) (-13.10, 2.12)

P-value .025e > .05e

N = number of patients; CI95 % = 95 % confidence interval.aEfficacy outcomes were evaluated across Months 1-3.bPatient-reported outcomes were evaluated at Month 3. MSQ role function restrictive domain responders weredefined as those with an improvement of ≥ 17.14 points for Chronic Migraine at Month 3.cStatistically significant after adjustment for multiple comparisons.dNot statistically significant after adjustment for multiple comparisons.eNot adjusted for multiple comparisons.

In patients who failed one or more prophylactic treatments for efficacy reasons, the treatmentdifference for the reduction of mean monthly MHDs observed between galcanezumab 120 mg andplacebo was -3.54 days (p < 0.001) and between galcanezumab 240 mg and placebo -1.37 days(p < 0.05). In patients failing two or more prophylactic treatments, the treatment differencewas -4.48 days (p < 0.001) between 120 mg and placebo and -1.86 days (p < 0.01) between 240 mgand placebo.

Sixty-four percent of the patients had acute headache medication overuse at baseline. In these patients,the treatment difference observed between galcanezumab 120 mg and placebo and betweengalcanezumab 240 mg and placebo for the reduction of MHDs in these patients wasrespectively -2.53 days (p < 0.001) and -2.26 days (p < 0.001).

Long term efficacy

Efficacy was sustained for up to 1 year in an open-label study in which patients with either episodic orchronic migraine (with an average baseline of 10.6 monthly MHDs) received galcanezumab120 mg/month (with an initial loading dose of 240 mg for the first month) or galcanezumab240 mg/month. 77.8 % of patients completed the treatment period. The overall mean reduction frombaseline in the number of monthly MHDs averaged over the treatment phase was 5.6 days for the120 mg dose group and 6.5 days for the 240 mg dose group. Over 72 % of patients completing thestudy reported a 50 % reduction in MHDs at month 12. In pooled data from studies EVOLVE-1 and

EVOLVE-2, more than 19 % of the patients treated with galcanezumab maintained a ≥ 50 % responsefrom Month 1 to Month 6 versus 8 % of the patients on placebo (p < 0.001).

Phase 3 study in a population with previous failure to 2 to 4 migraine preventive medicationcategories

Study CONQUER, in episodic and chronic migraine patients that experienced previous failures to 2 to4 prophylactic medication categories in the past 10 years, supports the main findings of the previousmigraine efficacy studies, i.e. galcanezumab treatment led to a mean reduction in monthly migraineheadache days (4.1 days compared to 1.0 days in the placebo group; p<.0001). Mean reduction inmonthly migraine headache days was also observed within the subpopulations of episodic migraine(2.9 days for galcanezumab compared with 0.3 days for placebo; p<.0001) and chronic migraine(5.9 days for galcanezumab compared with 2.2 days for placebo; p<.0001).

The European Medicines Agency has deferred the obligation to submit the results of studies withgalcanezumab in one or more subsets of the paediatric population in the prophylaxis of migraineheadaches (see section 4.2 for information on paediatric use).

Based on a population pharmacokinetic (PK) analysis, following a loading dose of 240 mg themaximum serum concentration (Cmax) of galcanezumab was approximately 30 μg/mL(27 % coefficient of variation, (CV)) and the time to Cmax was 5 days postdose.

Monthly doses of 120 mg or 240 mg achieved a steady-state Cmax (Cmax, ss) of approximately 28 μg/mL(35 % CV) or 54 μg/mL (31 % CV), respectively. The galcanezumab Cmax, ss at monthly doses of120 mg is achieved after the 240 mg loading dose.

Injection site location (abdomen, thigh, buttocks and arm) did not significantly influence theabsorption of galcanezumab.

Based on a population PK analysis, the apparent volume of distribution of galcanezumab was 7.3 L.

As a humanised IgG4 monoclonal antibody, galcanezumab is expected to be degraded into smallpeptides and amino acids via catabolic pathways in the same manner as endogenous IgG.

Based on a population PK analysis, the apparent clearance of galcanezumab was approximately0.008 L/hour and the half life of galcanezumab was 27 days.

Galcanezumab exposure increases proportionally with dose.

Based on a population PK analysis that included doses ranging from 5 - 300 mg, the rate ofabsorption, apparent clearance and apparent volume of distribution was independent of dose.

No dose adjustment is needed on the basis of age (18 to 65 years), sex, weight, race or ethnicity asthere was no clinically meaningful effect of these factors on the apparent clearance or apparent volumeof distribution of galcanezumab.

Specific clinical pharmacology studies to evaluate the effects of renal impairment and hepaticimpairment on the PK of galcanezumab have not been conducted. Renal elimination of IgGmonoclonal antibody is low. Similarly, IgG monoclonal antibodies are mainly eliminated viaintracellular catabolism and hepatic impairment is not expected to influence the clearance ofgalcanezumab. Based on a population PK analysis, bilirubin concentration or Cockcroft-Gaultcreatinine clearance (range: 24 to 308 mL/min) did not significantly influence the apparent clearanceof galcanezumab.

Non-clinical data revealed no special hazards for humans based on repeat-dose toxicity studiesconducted in rats and cynomolgus monkeys and safety pharmacology evaluations conducted incynomolgus monkeys at exposures approximately 10 to 80 times higher than clinical exposures inpatients receiving 240 mg.

Nonclinical studies have not been conducted to evaluate the carcinogenic or mutagenic potential ofgalcanezumab. There is no evidence to suggest that chronic treatment with galcanezumab wouldincrease the risk of carcinogenesis based on data from pharmacology and chronic toxicology studieswith galcanezumab, as well as an assessment of the literature regarding CGRP.

No effects on fertility parameters such as oestrous cycle, sperm analysis, or mating and reproductiveperformance were observed in rats that were administered galcanezumab (exposures approximately 4to 20 times the human exposure at 240 mg). In male fertility study, right testis weight wassignificantly reduced at exposures to 4 times the human exposure at 240 mg.

At Gestational Day 20, an increase in the number of foetuses and litters with short ribs and a decreasein the mean number of ossified caudal vertebrae occurred in the rat embryo-foetal toxicitydevelopment study at an exposure approximately 20 times the human exposure at 240 mg. Thesefindings were noted at no maternal toxicity and were considered to be related to galcanezumab butnon-adverse.

At Gestational Day 29, in rabbit embryo-foetal development toxicity study skull anomaly was found inone male foetus from mother treated with galcanezumab at an exposure approximately 33 times thehuman exposure at 240 mg.

In a juvenile toxicology study in which rats were administered galcanezumab twice weekly from

Postnatal Day 21 through 90, systemic effects were limited to reversible, minimal, nonadversedecreases in total bone mineral content and bone mineral density at exposures approximately 50 timesthe human exposure at 240 mg.

L-histidine

L-histidine hydrochloride monohydrate

Polysorbate 80

Sodium chloride

Water for injections

Not applicable.

2 years

Store in a refrigerator (2 ºC - 8 ºC).

Do not freeze.

Store in the original package in order to protect from light.

Emgality may be stored unrefrigerated for up to 7 days when stored at temperatures up to 30 °C. Ifthese conditions are exceeded, the pre-filled pen must be discarded.

Type I clear glass syringe. The syringe is encased in a disposable, single-dose pen. Packs of 1, 2 or3 pre-filled pens. Not all pack sizes may be marketed.

The instructions for using the pen included with the Package Leaflet, must be followed carefully. Thepre-filled pen is for total use only.

The pre-filled pen should be inspected visually prior to administration. Emgality should not be used ifthe solution is cloudy, discoloured or contains particles, or if any part of the device appears to bedamaged.

Do not shake.

Any unused medicinal product or waste material should be disposed of in accordance with localrequirements.

Eli Lilly Nederland B.V., Orteliuslaan 1000, 3528 BD Utrecht, The Netherlands

EU/1/18/1330/001

EU/1/18/1330/002

EU/1/18/1330/005

Date of first authorisation: 14 November 2018

Date of latest renewal: 01 September 2023

Detailed information on this medicinal product is available on the website of the European Medicines

Agency https://www.ema.europa.eu.