WAINZUA 45mg 45mg / 0.8ml solution for injection in pre-filled pen medication leaflet

Wainzua 45 mg solution for injection in pre-filled pen

Each pre-filled pen contains 45 mg eplontersen (as eplontersen sodium) in 0.8 ml of solution.

Each ml contains 56 mg eplontersen (as eplontersen sodium).

For the full list of excipients, see section 6.1.

Solution for injection (injection).

Clear, colourless to yellow solution (pH of approximately 7.4 and osmolality 250 to 330 mOsm/kg).

Wainzua is indicated for the treatment of hereditary transthyretin-mediated amyloidosis (ATTRv) inadult patients with stage 1 or stage 2 polyneuropathy.

Treatment should be prescribed and supervised by a physician experienced in the treatment of patientswith hereditary transthyretin-mediated amyloidosis.

The recommended dose of eplontersen is 45 mg administered monthly.

Vitamin A supplementation at approximately, but not exceeding, 2 500 IU to 3 000 IU vitamin A perday is advised for patients treated with Wainzua (see section 4.4).

Treatment should be initiated as early as possible after symptom onset (see section 5.1).

The decision to continue treatment in those patients whose disease progresses to stage 3polyneuropathy should be taken at the discretion of the physician based on the overall benefit and riskassessment.

If a dose of Wainzua is missed, then the next dose should be administered as soon as possible. Dosingshould be resumed at monthly intervals from the date of the last dose; a double dose should not beadministered.

No dose adjustment is required in elderly patients (≥ 65 years of age) (see section 5.2).

No dose adjustment is necessary in patients with mild to moderate renal impairment (estimatedglomerular filtration rate [eGFR] ≥ 45 to < 90 mL/min/1.73 m2). Eplontersen has not been studied inpatients with eGFR < 45 mL/min/1.73 m2 or end-stage renal disease (see section 5.2) and should onlybe used in these patients if the anticipated clinical benefit outweighs the potential risk.

No dose adjustment is necessary in patients with mild hepatic impairment. Eplontersen has not beenstudied in patients with moderate or severe hepatic impairment and should only be used in thesepatients if the anticipated clinical benefit outweighs the potential risk (see section 5.2).

Patients undergoing liver transplant

The safety and efficacy of Wainzua have not been evaluated in patients undergoing liver transplant.

No data are available.

The safety and efficacy of Wainzua in children and adolescents below 18 years of age have not beenestablished. No data are available (see section 5.1).

Wainzua is for subcutaneous use. Wainzua is a pre-filled pen for single-use only.

The first injection administered by the patient or caregiver should be performed under the guidance ofan appropriately qualified health care professional. Patients and/or caregivers should be trained in thesubcutaneous administration of Wainzua.

The pre-filled pen should be removed from refrigerated storage at least 30 minutes before use andallowed to reach room temperature prior to injection. Other warming methods should not be used.

Inspect solution visually before use. The solution should appear colourless to yellow. Do not use ifcloudiness, particulate matter, or discolouration is observed prior to administration.

If self-administered, Wainzua should be injected in the abdomen or upper thigh region. If a caregiveradministers the injection, the back of the upper arm can also be used.

Wainzua should not be injected into skin that is bruised, tender, red, or hard, into scars or damagedskin, the area around the navel should be avoided.

Comprehensive instructions for administration using the pre-filled pen are provided in the‘Instructions for Use’.

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

Vitamin A deficiency

Based on the mechanism of action, Wainzua is expected to reduce serum vitamin A (retinol) belownormal levels (see section 5.1). Serum vitamin A levels below the lower limit of normal should becorrected and any ocular symptoms or signs related to vitamin A deficiency should be evaluated priorto initiation of treatment with Wainzua.

Patients receiving Wainzua should take oral supplementation of approximately, but not exceeding,2 500 IU (female) to 3 000 IU (male) of vitamin A per day to reduce the potential risk of ocularsymptoms due to vitamin A deficiency. Referral for ophthalmological assessment is recommended ifpatients develop ocular symptoms consistent with vitamin A deficiency, including reduced nightvision or night blindness, persistent dry eyes, eye inflammation, corneal inflammation or ulceration,corneal thickening or corneal perforation.

During the first 60 days of pregnancy, both too high and too low vitamin A levels may be associatedwith an increased risk of foetal malformation. Therefore, pregnancy should be excluded beforetreatment initiation and women of childbearing potential should practise effective contraception (seesection 4.6). If a woman intends to become pregnant, Wainzua and vitamin A supplementation shouldbe discontinued, and serum vitamin A levels should be monitored and have returned to normal beforeconception is attempted.

In the event of an unplanned pregnancy, Wainzua should be discontinued. Due to the long half-life ofeplontersen (see section 5.2), a vitamin A deficit may even develop after cessation of treatment. Norecommendation can be given whether to continue or discontinue vitamin A supplementation duringthe first trimester of an unplanned pregnancy. If vitamin A supplementation is continued, the dailydose should not exceed 3 000 IU per day, due to the lack of data supporting higher doses. Thereafter,vitamin A supplementation of 2 500 IU to 3 000 IU per day should be resumed in the second and thirdtrimesters if serum vitamin A levels have not yet returned to normal, because of the increased risk ofvitamin A deficiency in the third trimester.

It is not known whether vitamin A supplementation in pregnancy will be sufficient to preventvitamin A deficiency if the pregnant female continues to receive Wainzua. However, increasingvitamin A supplementation to above 3 000 IU per day during pregnancy is unlikely to correct serumretinol levels due to the mechanism of action of eplontersen and may be harmful to the mother andfoetus.

This medicinal product contains less than 1 mmol sodium (23 mg) per dose of 0.8 ml, that is to sayessentially ‘sodium-free’.

No interaction studies have been performed.

In vitro studies indicate that eplontersen is not a substrate or inhibitor of transporters, does not interactwith highly plasma protein bound medicinal products, and is not an inhibitor or inducer of CYPenzymes.

Wainzua will reduce the plasma levels of vitamin A, which is crucial for normal foetal development. Itis not known whether vitamin A supplementation will be sufficient to reduce the risk to the foetus (seesection 4.4). For this reason, pregnancy should be excluded before initiation of Wainzua therapy andwomen of child-bearing potential should practice effective contraception.

If a woman intends to become pregnant, Wainzua and vitamin A supplementation should bediscontinued, and serum vitamin A levels should be monitored and have returned to normal beforeconception is attempted (see section 4.4). Serum vitamin A levels may remain reduced for more than15 weeks after the last dose of treatment.

There are no data on the use of eplontersen in pregnant women. Animal studies are insufficient withrespect to reproductive toxicity (see section 5.3). Due to the potential teratogenic risk arising fromunbalanced vitamin A levels, Wainzua should not be used during pregnancy and in women ofchildbearing potential not using contraception. In case of pregnancy, close monitoring of the foetusand vitamin A status should be carried out, especially during the first trimester (see section 4.4).

It is unknown whether eplontersen or its metabolites are excreted in human milk. A risk to thebreastfed child cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from

Wainzua therapy, taking into account the benefit of breast feeding for the child and the benefit oftherapy for the woman.

There is no information available on the effects of eplontersen on human fertility. No impact on maleor female fertility was detected in animal studies (see section 5.3).

Eplontersen has no or negligible influence on the ability to drive and use machines.

The most frequent adverse reactions during treatment with eplontersen were vitamin A decreased(97% of patients) and vomiting (9% of patients).

The safety data reflects exposure to Wainzua in 144 patients with polyneuropathy caused by ATTRv(ATTRv-PN) randomised to eplontersen and who received at least one dose of eplontersen. 130patients completed treatment with eplontersen through Week 85. The mean duration of treatment was541 days (range: 57 to 582 days).

Adverse reactions are organised by MedDRA System Organ Class (SOC). Within each SOC, preferredterms are arranged by decreasing frequency and then by decreasing seriousness. Frequencies ofoccurrence of adverse reactions are defined as: 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) and notknown (cannot be estimated from available data).

Table 1: Adverse reactions reported for Wainzua

System organ class Adverse reaction Frequency

Gastrointestinal disorders Vomiting Common

Injection site erythema Common

General disorders and

Injection site pain Commonadministration site conditions

Injection site pruritus Common

Investigations Vitamin A decreased Very common*

* Based on laboratory findings of vitamin A below the lower limit of normal during the study.

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.

There is no specific treatment for an overdose with eplontersen. In the event of an overdose,supportive medical care should be provided.

Pharmacotherapeutic group: Other nervous system drugs, ATC code: N07XX21.

Eplontersen is a N-acetylgalactosamine (GalNAc)-conjugated 2′-O-2-methoxyethyl-modified chimericgapmer antisense oligonucleotide (ASO) with a mixed backbone of phosphorothioate and phosphatediester internucleotide linkages. The GalNAc conjugate enables targeted delivery of the ASO tohepatocytes. The selective binding of eplontersen to the transthyretin (TTR) messenger RNA (mRNA)within the hepatocytes causes the degradation of both mutant and wild type (normal) TTR mRNA.

This prevents the synthesis of TTR protein in the liver, resulting in significant reductions in the levelsof mutated and wild type TTR protein secreted by the liver into the circulation.

In the clinical study in patients with ATTRv-PN receiving eplontersen, a decrease in serum TTRconcentrations was observed at the first assessment (Week 5) and TTR concentrations continued todecrease through Week 35. A sustained reduction of TTR concentration was observed throughout theduration of the treatment (85 weeks). Mean (SD) for serum TTR percent reduction from baseline was82.1% (11.7) at Week 35, 83.0% (10.4) at Week 65 and 81.8% (13.4) at Week 85 when treated witheplontersen. Similar reduction from baseline in serum TTR concentrations was observed regardless ofsex, race, age, region, body weight, cardiomyopathy status, previous treatment, Val30Met mutationstatus, disease stage, and familial amyloid cardiomyopathy clinical diagnosis at baseline.

TTR is a carrier protein for retinol binding protein 4, which is the principal carrier of vitamin A(retinol). Therefore, a reduction in plasma TTR is expected to result in the reduction of plasma retinollevels to below the lower limit of normal.

The efficacy and safety of eplontersen was evaluated in a randomised, multicentre, open-label, trial(NEURO-TTRansform) that included a total of 168 adult patients with ATTRv-PN. Patients wererandomised in a 6:1 ratio to receive subcutaneous injection of eplontersen 45 mg every 4 weeks(N=144) or inotersen 284 mg weekly (N=24) as a reference group. Of the 144 patients randomised toeplontersen, 140 (97.2 %) patients completed treatment through Week 35, 135 (93.8%) completedtreatment through Week 65.

An external placebo control consisted of a placebo cohort of patients from the inotersen pivotal study(NEURO-TTR): randomised, double-blind, placebo-controlled, multicentre clinical trial in adultpatients with ATTRv-PN. That cohort received subcutaneous injections of placebo once weekly. Bothstudies employed identical eligibility criteria.

The characteristics of the eplontersen and external placebo groups were generally similar, andpotential imbalances in key baseline characteristics (Val30Met mutation status, disease stage, andprevious treatment) were accounted for in the prespecified statistical analysis.

Of the 144 patients randomised to eplontersen, the median patient age at baseline was 51.5 years(range 24 to 82), 30.6% were ≥ 65 years old, and 69.4% of patients were male. Twenty (20) different

TTR variants were represented: Val30Met (59.0%), Phe64Leu (3.5%), Leu58His (2.8%), Thr60Ala(2.8%), Val122Ile (2.8%), Ser77Tyr (2.1%), Ser50Arg (1.4%), Thr49Ala (0.7%), Glu89Gln (0.7%),and Other (24.3%, includes Ala97Ser (15%)). At baseline, 79.9% of patients had stage 1 disease(unimpaired ambulation; mild sensory, motor, and autonomic neuropathy in the lower limbs), 20.1%had stage 2 disease (assistance with ambulation required; moderate impairment of the lower limbs,upper limbs, and trunk), and there were no patients with stage 3 disease. 69.4% of patients had priortreatment with either tafamidis or diflunisal.

At Week 66 analysis, the co-primary endpoints included percent change from baseline in serum TTRconcentration at Week 65, change from baseline in mNIS+7 score and change from baseline in

Norfolk QoL-DN total score at Week 66, all when eplontersen was compared to placebo.

The mNIS+7 is an objective assessment of neuropathy and comprises the NIS and Modified +7composite scores. In the version of the mNIS+7 used in the trial, the NIS objectively measures deficitsin cranial nerve function, muscle strength, reflexes, and sensations, and the Modified +7 assesses heartrate response to deep breathing, quantitative sensory testing (touch-pressure and heat-pain), andperipheral nerve electrophysiology. The validated version of the mNIS+7 score used in the trial had arange of -22.3 to 346.3 points, with higher scores representing a greater severity of disease.

The Norfolk QoL-DN scale is a patient-reported assessment that evaluates the subjective experience ofneuropathy in the following domains: physical functioning/large fibre neuropathy, activities of dailyliving, symptoms, small fibre neuropathy, and autonomic neuropathy. The version of the Norfolk

QoL-DN that was used in the trial had a range from -4 to 136 points, with higher scores representinggreater impairment.

Other secondary endpoints were formally tested hierarchically at Week 66 analysis and includedchange from baseline in neuropathy symptoms and change score, in the physical component summaryscore of short form 36-item health survey (version 2), in polyneuropathy disability score and innutritional status (modified body mass index).

Treatment with eplontersen in NEURO-TTRansform study demonstrated statistically significantimprovements in all endpoints at both Week 35 and Week 66 (see Table 2) compared to the externalplacebo group (all p < 0.0001).

Table 2: Summary of clinical efficacy results from NEURO-TTRansform Study

Mean (SD) LSM Change/Percent Change Eplontersen-from Baseline, (Estimate SE) Placebo*

Analysis/[95% CI] Difference in p-value

Endpoint

LSM

Placebo* Eplontersen Placebo* Eplontersen[95% CI]

Safety analysis N = 60 N = 144 N = 60 N = 144set

Serum TTR, g/L 1

Baseline 0.15 (0.04) 0.23 (0.08)

Week 35 -14.7% (2.2) -81.3% (1.8) -66.6% p < 0.0001[-18.96, -10.44] [-84.83, -77.71] [-71.61, -61.53]

Week 65 0.14 (0.04) 0.04 (0.02) -10.2% (2.2) -80.2% (1.8) -70.1% p < 0.0001[-14.43, -5.87] [-83.75, -76.72] [-75.02, -65.15]mNIS+7composite score 1

Baseline 74.1 (39.0) 79.8 (42.3)

Week 35 9.9 (1.9) 1.1 (1.8) -8.8 p = 0.0001[6.29, 13.56] [-2.47, 4.77] [-13.21, -4.34]

Week 66 96.6 (50.2) 79.7 (44.9) 26.3 (2.6) 3.2 (2.5) -23.1 p < 0.0001[21.32, 31.38] [-1.75, 8.18] [-29.26, -17.01]

Norfolk QOL-DNtotal score 1

Baseline 48.6 (27.0) 43.3 (26.2)

Week 35 8.4 (2.1) -2.8 (2.1) -11.3 p < 0.0001[4.30, 12.58] [-6.87, 1.19] [-16.26, -6.30]

Week 66 58.9 (32.0) 35.6 (26.3) 13.7 (2.4) -5.5 (2.4) -19.3 p < 0. 0001[8.92, 18.50] [-10.19, -0.91] [-24.99, -13.53]

Full analysis set N = 59 N = 141 N = 59 N = 141

Neuropathysymptom and 8.2 -0.0 -8.2p < 0.0001change score, [6.24, 10.12] [-1.92, 1.86] [-10.65, -5.76]

Week 66 2

Physicalcomponent score

- 4.46 0.85 5.31of short form 36 p < 0.0001[-6.139, -2.770] [-0.711, 2.412] [3.195, 7.416]item healthsurvey, Week 65 2

Modified body -90.8

- 8.1 82.7mass index, [-112.84, p < 0.0001[-28.55, 12.42] [54.64, 110.76]

Week 65 2 -68.69]

* External placebo group from another randomised controlled trial (NEURO-TTR).1 Based on an ANCOVA with a reference-based multiple imputation approach for missing data, adjusted bypropensity score weights with fixed categorical effects for treatment, time, treatment-by-time interaction,disease stage, Val30M mutation, previous treatment, fixed covariates for the baseline value and the baseline-by-time interaction. In the reference-based imputation approach, missing data in the placebo group and missingdata in eplontersen treatment group while on treatment, is imputed under a within treatment arm missing atrandom assumption. For a patient in eplontersen treatment group who discontinued, missing data were imputedbased on the placebo group.2 Based on a MMRM adjusted by propensity score weights with fixed categorical effects for treatment, time,treatment-by-time interaction, disease stage, Val30M mutation, previous treatment, fixed covariates for thebaseline value and the baseline-by-time interaction.

ANCOVA = analysis of covariance; CI = confidence interval; LSM = least squares mean; MMRM = mixedeffects model with repeated measures; mNIS+7 = modified neuropathy impairment score +7; N = number ofparticipants in group; Norfolk QoL-DN = Norfolk quality of life - diabetic neuropathy questionnaire;

SD = standard deviation; SE = standard error; TTR = transthyretin.

The secondary endpoint of change from baseline in PND score at Week 65 was statistically significantin favor of eplontersen (p= 0.02). More patients in the eplontersen group experienced improvementfrom baseline in PND score than in the external placebo group (5.7% vs 3.4%) and fewer patients inthe eplontersen group experienced a worsening from baseline than in the external placebo group(12.8% vs. 22.0%).

Patients receiving eplontersen experienced similar improvements relative to placebo in the reductionof serum TTR concentration, mNIS+7 composite and Norfolk QoL-DN total scores across allsubgroups including age, sex, race, region, Val30Met mutation status, cardiomyopathy status, familialamyloid cardiomyopathy clinical diagnosis at baseline and disease stage.

Through the end of treatment with eplontersen at Week 85, reduction of TTR concentration and theobserved effect in mNIS+7 composite score were sustained, and the mean Norfolk QoL-DN totalscore remained stable.

In the clinical study in patients with ATTRv-PN, after an 84-week treatment period (median treatmentduration of 561 days (80 weeks), range: 57 to 582 days), 58 patients (40.3%) developedtreatment-emergent anti-drug antibodies (ADAs). ADA to eplontersen tended to be persistent with alate onset (median onset 223 days) and low titer (median peak titer 200). In the patients who testedpositive for anti-eplontersen antibodies, there was no clinically meaningful impact on the efficacy,safety, pharmacokinetics, or pharmacodynamics of eplontersen.

The European Medicines Agency has waived the obligation to submit the results of studies witheplontersen in all subsets of the paediatric population in the treatment of transthyretin amyloidosis (seesection 4.2 for information on paediatric use).

The pharmacokinetic properties of Wainzua were evaluated by measuring plasma concentrations ofeplontersen following subcutaneous administration of single and multiple doses (once every 4 weeks)in healthy subjects and multiple doses (once every 4 weeks) in patients with ATTRv-PN.

Following subcutaneous administration, eplontersen is absorbed rapidly into the systemic circulationwith the time to maximum plasma concentrations of approximately 2 hours, based on populationestimates. Population estimates of steady state maximum concentrations (Cmax), trough concentrations(Ctrough), and area under the curve (AUCτ) were 0.218 μg/ml, 0.0002 μg/ml, and 1.95 μg h/ml,respectively, following 45 mg once every 4 weeks dosing in patients with ATTRv-PN. Noaccumulation of eplontersen Cmax and AUC was observed in plasma after repeated dosing (once every4 weeks). Accumulation was observed in Ctrough, and steady-state was reached after approximately17 weeks.

Eplontersen is highly bound to human plasma proteins (> 98%). The population estimates for theapparent central volume of distribution is 12.9 l and the apparent peripheral volume of distribution is11 100 l. Eplontersen is expected to distribute primarily to the liver and kidney cortex aftersubcutaneous dosing.

Eplontersen is metabolised by endo- and exonucleases into short oligonucleotide fragments of varyingsizes primarily within the liver. There were no major circulating metabolites in humans.

Oligonucleotide therapeutics, including eplontersen, are not metabolised by CYP enzymes.

Eplontersen is primarily eliminated by metabolism followed by renal excretion of the shortoligonucleotide metabolites. The mean fraction of unchanged ASO eliminated in urine was less than1% of the administered dose within 24 hours. The terminal elimination half-life is approximately3 weeks based on population estimates.

Eplontersen Cmax and AUC showed a slightly greater than dose-proportional increase following singlesubcutaneous doses ranging from 45 to 120 mg (i.e. 1 to 2.7 times the recommended dose) in healthyvolunteers.

Based on the population pharmacokinetic, body weight, sex, race, and Val30Met mutation status areunlikely to have a clinically meaningful effect on eplontersen exposure. Definitive assessments werelimited in some cases as covariates were limited by the overall low numbers.

No overall differences in pharmacokinetics were observed between adult and elderly (≥ 65 years ofage) patients.

No formal clinical studies have been conducted to investigate the effect of renal impairment oneplontersen pharmacokinetics. A population pharmacokinetic and pharmacodynamic analysis showedno clinically meaningful differences in the pharmacokinetics or pharmacodynamics of eplontersenbased on mild and moderate renal impairment (eGFR ≥ 45 to < 90 ml/min). Eplontersen has not beenstudied in patients with eGFR < 45 ml/min or in patients with end-stage renal disease.

No formal clinical studies have been conducted to investigate the effect of hepatic impairment oneplontersen. A population pharmacokinetic and pharmacodynamic analysis showed no clinicallymeaningful differences in the pharmacokinetics or pharmacodynamics of eplontersen based on mildhepatic impairment (total bilirubin ≤ 1 × ULN and AST > 1 × ULN, or total bilirubin > 1.0 to1.5 × ULN and any AST). Eplontersen has not been studied in patients with moderate hepaticimpairment (total bilirubin > 1.5 to 3 × ULN and any AST) or severe hepatic impairment (totalbilirubin > 3 to 10 × ULN and any AST) or in patients with prior liver transplant.

General toxicology

Repeated administration of eplontersen at 24 mg/kg/week for 13 weeks or 25 mg/kg/month for9 months in monkeys reduced TTR protein in plasma by 69% and 52%, respectively. There were notoxicologically relevant findings related to this pharmacologic inhibition of TTR expression.

Most of the findings observed after repeated subcutaneous dosing for up to 6 months in mice and9 months in monkeys were non-adverse and related to the uptake and accumulation of eplontersen byvarious cell types in multiple organs of all tested animal species including monocytes/macrophages,kidney proximal tubular epithelia, Kupffer cells of the liver, and histiocytic cell infiltrates in lymphnodes and injection sites.

In a single monkey in the 13 week toxicity study, severely decreased platelet counts associated withspontaneous haemorrhage, presented as haematoma and petechiae, were observed at the highest dosetested (24 mg/kg/week). Similar findings were not observed at the NOAEL of 6 mg/kg/week inmonkeys, which corresponds to more than 70-fold the human AUC at the recommended therapeuticeplontersen dose.

Eplontersen did not exhibit genotoxic potential in vitro and in vivo and was not carcinogenic in ras.H2transgenic mice.

Eplontersen had no effects on fertility or embryo-foetal development in mice up to 38-fold (based onhuman equivalent dose) to the recommended human monthly dose of 45 mg. Eplontersen is notpharmacologically active in mice. Consequently, only effects related to the chemistry of eplontersencould be captured in this study. However, no effect on fertility or embryo-foetal development wasnoted with a mouse-specific analogue of eplontersen in mice, which was associated with > 90%inhibition of TTR mRNA expression.

Sodium dihydrogen phosphate dihydrate

Disodium hydrogen phosphate anhydrous

Sodium chloride

Hydrochloric acid (for pH adjustment)

Sodium hydroxide (for pH adjustment)

Water for injections

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinalproducts.

3 years.

Wainzua may be stored in original carton unrefrigerated for up to 6 weeks below 30°C. If not usedwithin 6 weeks, it should be discarded.

Store in a refrigerator (2°C - 8°C). Do not freeze.

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

0.8 ml sterile solution for injection in a single-use, type I glass syringe with a staked 27-gauge ½ inch(12.7 mm) stainless steel needle, rigid needle shield, and siliconised chlorobutyl elastomer stopper in apre-filled pen.

Pack size of one single-use pre-filled pen.

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

AstraZeneca AB

SE-151 85 Södertälje

Sweden

EU/1/24/1875/001

Date of first authorisation:

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

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