LEQVIO 284mg 189mg / ml injectible solution medication leaflet

Leqvio 284 mg solution for injection in pre-filled syringe

Each pre-filled syringe contains inclisiran sodium equivalent to 284 mg inclisiran in 1.5 ml solution.

Each ml contains inclisiran sodium equivalent to 189 mg inclisiran.

For the full list of excipients, see section 6.1.

Solution for injection (injection).

The solution is clear, colourless to pale yellow, and essentially free of particulates.

Leqvio is indicated in adults with primary hypercholesterolaemia (heterozygous familial andnon-familial) or mixed dyslipidaemia, as an adjunct to diet:

* in combination with a statin or statin with other lipid-lowering therapies in patients unable toreach LDL-C goals with the maximum tolerated dose of a statin, or

* alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant,or for whom a statin is contraindicated.

The recommended dose is 284 mg inclisiran administered as a single subcutaneous injection: initially,again at 3 months, followed by every 6 months.

If a planned dose is missed by less than 3 months, inclisiran should be administered and dosingcontinued according to the patient’s original schedule.

If a planned dose is missed by more than 3 months, a new dosing schedule should be started -inclisiran should be administered initially, again at 3 months, followed by every 6 months.

Inclisiran can be administered immediately after the last dose of a monoclonal antibody PCSK9inhibitor. To maintain LDL-C lowering it is recommended that inclisiran is administered within2 weeks after the last dose of a monoclonal antibody PCSK9 inhibitor.

No dose adjustment is necessary in elderly patients.

No dose adjustments are necessary for patients with mild (Child-Pugh class A) or moderate(Child-Pugh class B) hepatic impairment. No data are available in patients with severe hepaticimpairment (Child-Pugh class C) (see section 5.2). Inclisiran should be used with caution in patientswith severe hepatic impairment.

No dose adjustments are necessary for patients with mild, moderate or severe renal impairment orpatients with end-stage renal disease (see section 5.2). There is limited experience with inclisiran inpatients with severe renal impairment. Inclisiran should be used with caution in these patients. Seesection 4.4 for precautions to take in case of haemodialysis.

The safety and efficacy of inclisiran in children aged less than 18 years have not yet been established.

No data are available.

Subcutaneous use.

Inclisiran is for subcutaneous injection into the abdomen; alternative injection sites include the upperarm or thigh. Injections should not be given into areas of active skin disease or injury such assunburns, skin rashes, inflammation or skin infections.

Each 284 mg dose is administered using a single pre-filled syringe. Each pre-filled syringe is forsingle use only.

Inclisiran is intended for administration by a healthcare professional.

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

The effect of haemodialysis on inclisiran pharmacokinetics has not been studied. Considering thatinclisiran is eliminated renally, haemodialysis should not be performed for at least 72 hours afterinclisiran dosing.

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

Inclisiran is not a substrate for common drug transporters and, although in vitro studies were notconducted, it is not anticipated to be a substrate for cytochrome P450. Inclisiran is not an inhibitor orinducer of cytochrome P450 enzymes or common drug transporters. Therefore, inclisiran is notexpected to have clinically significant interactions with other medicinal products. Based on the limiteddata available, clinically meaningful interactions with atorvastatin, rosuvastatin or other statins are notexpected.

There are no or limited amount of data from the use of inclisiran in pregnant women. Animal studiesdo not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

As a precautionary measure, it is preferable to avoid the use of inclisiran during pregnancy.

It is unknown whether inclisiran is excreted in human milk. Available pharmacodynamic/toxicologicaldata in animals have shown excretion of inclisiran in milk (see section 5.3). A risk to newborns/infantscannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain frominclisiran therapy, taking into account the benefit of breast-feeding for the child and the benefit oftherapy for the woman.

No data on the effect of inclisiran on human fertility are available. Animal studies did not show anyeffects on fertility (see section 5.3).

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

The only adverse reactions associated with inclisiran were adverse reactions at the injection site(8.2%).

Adverse reactions are presented by system organ class (Table 1). Frequency categories are defined as:

very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000to <1/1,000); very rare (<1/10,000) and not known (cannot be estimated from the available data).

Table 1 Adverse reactions reported in patients treated with inclisiran

System organ class Adverse reaction Frequency category

General disorders and Adverse reactions at the Commonadministration site conditions injection site11 See section “Description of selected adverse reactions”

Adverse reactions at the injection site occurred in 8.2% and 1.8% of inclisiran and placebo patients,respectively, in the pivotal studies. The proportion of patients in each group who discontinuedtreatment due to adverse reactions at the injection site was 0.2% and 0.0%, respectively. All of theseadverse reactions were mild or moderate in severity, transient and resolved without sequelae. The mostfrequently occurring adverse reactions at the injection site in patients treated with inclisiran wereinjection site reaction (3.1%), injection site pain (2.2%), injection site erythema (1.6%), and injectionsite rash (0.7%).

Of the 1,833 patients treated with inclisiran in the pivotal studies, 981 (54%) were 65 years of age orolder, while 239 (13%) were 75 years of age or older. No overall differences in safety were observedbetween these patients and younger patients.

In the pivotal studies 1,830 patients were tested for anti-drug antibodies. Confirmed positivity wasdetected in 1.8% (33/1,830) of patients prior to dosing and in 4.9% (90/1,830) of patients during the18 months of treatment with inclisiran. No clinically significant differences in the clinical efficacy,safety or pharmacodynamic profiles of inclisiran were observed in the patients who tested positive foranti-inclisiran antibodies.

In the phase III clinical studies, there were more frequent elevations of serum hepatic transaminasesbetween >1x the upper limit of normal (ULN) and ≤3x ULN in patients on inclisiran (ALT: 19.7% and

AST: 17.2%) than in patients on placebo (ALT: 13.6% and AST: 11.1%). These elevations did notprogress to exceed the clinically relevant threshold of 3x ULN, were asymptomatic and were notassociated with adverse reactions or other evidence of liver dysfunction.

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.

No clinically relevant adverse reactions were observed in healthy volunteers who received inclisiran atdoses up to three times the therapeutic dose. No specific treatment for inclisiran overdose is available.

In the event of an overdose, the patient should be treated symptomatically, and supportive measuresinstituted as required.

Pharmacotherapeutic group: lipid modifying agents, other lipid modifying agents, ATC code:

C10AX16

Inclisiran is a cholesterol-lowering, double-stranded, small interfering ribonucleic acid (siRNA),conjugated on the sense strand with triantennary N-acetylgalactosamine (GalNAc) to facilitate uptakeby hepatocytes. In hepatocytes, inclisiran utilises the RNA interference mechanism and directscatalytic breakdown of mRNA for proprotein convertase subtilisin kexin type 9. This increases LDL-Creceptor recycling and expression on the hepatocyte cell surface, which increases LDL-C uptake andlowers LDL-C levels in the circulation.

Following a single subcutaneous administration of 284 mg inclisiran, LDL-C reduction was apparentwithin 14 days post-dose. Mean reductions of 49-51% for LDL-C were observed 30 to 60 dayspost-dose. At day 180, LDL-C levels were still reduced by approximately 53%.

In clinical studies and some publications, the 284 mg inclisiran dose is equivalent and referred to as300 mg inclisiran sodium salt.

The efficacy of inclisiran was evaluated in three phase III studies in patients with atheroscleroticcardiovascular disease (ASCVD) (coronary heart disease, cerebrovascular disease or peripheral arterydisease), ASCVD risk equivalents (type 2 diabetes mellitus, familial hypercholesterolaemia, or10-year risk of 20% or greater of having a cardiovascular event assessed by Framingham Risk Scoreor equivalent) and/or familial hypercholesterolaemia (FH). Patients were taking a maximally tolerateddose of statin with or without other lipid-modifying therapy and required additional LDL-C reduction(patients unable to reach their treatment goals). Approximately 17% of patients were statin intolerant.

Patients were administered subcutaneous injections of 284 mg inclisiran or placebo on day 1, day 90,day 270 and day 450. Patients were followed until day 540.

The effect of inclisiran on cardiovascular morbidity and mortality has not yet been determined.

In the phase III pooled analysis, subcutaneously administered inclisiran lowered LDL-C between 50%and 55% as early as day 90 (Figure 1), which was maintained during long-term therapy. Maximal

LDL-C reduction was achieved at day 150 following a second administration. Small but statisticallysignificant increased LDL-C reductions up to 65% were associated with lower baseline LDL-C levels(approximately <2 mmol/l [77 mg/dl]), higher baseline PCSK9 levels and higher statin doses andstatin intensity.

Figure 1 Mean percentage change from baseline LDL-C in patients with primaryhypercholesterolaemia and mixed dyslipidaemia treated with inclisiran compared toplacebo (pooled analysis)

Inclisiran Placebo

No. of patients

Placebo

Inclisiran

Two studies were conducted in patients with ASCVD and ASCVD risk equivalents (ORION-10 and

ORION-11). Patients were taking a maximally tolerated dose of statins with or without otherlipid-modifying therapy, such as ezetimibe, and required additional LDL-C reduction. As lowering

LDL-C is expected to improve cardiovascular outcomes, the co-primary endpoints in each study werethe percentage change in LDL-C from baseline to day 510 relative to placebo and the time-adjustedpercentage change in LDL-C from baseline after day 90 and up to day 540 to estimate the integratedeffect on LDL-C over time.

ORION-10 was a multicentre, double-blind, randomised, placebo-controlled 18-month studyconducted in 1,561 patients with ASCVD.

The mean age at baseline was 66 years (range: 35 to 90 years), 60% were ≥65 years old, 31% werewomen, 86% were White, 13% were Black, 1% were Asian and 14% were Hispanic or Latinoethnicity. The mean baseline LDL C was 2.7 mmol/l (105 mg/dl). Sixty-nine percent (69%) weretaking high-intensity statins, 19% were taking medium-intensity statins, 1% were taking low-intensitystatins and 11% were not on a statin. The most commonly administered statins were atorvastatin androsuvastatin.

Inclisiran significantly reduced the mean percentage change in LDL-C from baseline to day 510compared to placebo by 52% (95% CI: -56%, -49%; p <0.0001) (Table 2).

Inclisiran also significantly reduced the time-adjusted percentage change in LDL-C from baseline afterday 90 and up to day 540 by 54% compared to placebo (95% CI: -56%, -51%; p <0.0001). Foradditional results, see Table 2.

Mean percentage change from baseline

Table 2 Mean percentage change from baseline and difference from placebo in lipidparameters at day 510 in ORION-10

Treatment group LDL-C Total Non-HDL-C Apo-B Lp(a)*cholesterol

Mean baseline 105 181 134 94 122value in mg/dl**

Day 510 (mean percentage change from baseline)

Placebo (n=780) 1 0 0 -2 4

Inclisiran (n=781) -51 -34 -47 -45 -22

Difference from -52 -33 -47 -43 -26placebo (LS mean) (-56, -49) (-35, -31) (-50, -44) (-46, -41) (-29, -22)(95% CI)

*At day 540; median percentage change in Lp(a) values

**Mean baseline value in nmol/l for Lp(a)

At day 510, the LDL-C target of <1.8 mmol/l (70 mg/dl) was achieved by 84% of inclisiran patientswith ASCVD compared to 18% of placebo patients.

Consistent and statistically significant (p<0.0001) reductions in percentage change in LDL-C frombaseline to day 510 and time-adjusted percentage change in LDL-C from baseline after day 90 and upto day 540 were observed across all subgroups irrespective of baseline demographics, baseline diseasecharacteristics (including gender, age, body mass index, race and baseline statin use), comorbiditiesand geographic regions.

ORION-11 was an international, multicentre, double-blind, randomised, placebo-controlled 18-monthstudy which evaluated 1,617 patients with ASCVD or ASCVD risk equivalents. More than 75% ofpatients were receiving a high-intensity statin background treatment, 87% of patients had ASCVD and13% were ASCVD risk equivalent.

The mean age at baseline was 65 years (range: 20 to 88 years), 55% were ≥65 years old, 28% werewomen, 98% were White, 1% were Black ,1% were Asian and 1% were Hispanic or Latino ethnicity.

The mean baseline LDL-C was 2.7 mmol/l (105 mg/dl). Seventy-eight percent (78%) were takinghigh-intensity statins, 16% were taking medium-intensity statins, 0.4% were taking low-intensitystatins and 5% were not on a statin. The most commonly administered statins were atorvastatin androsuvastatin.

Inclisiran significantly reduced the mean percentage change in LDL-C from baseline to day 510compared to placebo by 50% (95% CI: -53%, -47%; p<0.0001) (Table 3).

Inclisiran also significantly reduced time-adjusted percentage change in LDL-C from baseline afterday 90 and up to day 540 by 49% compared to placebo (95% CI: -52%, -47%; p<0.0001). Foradditional results, see Table 3.

Table 3 Mean percentage change from baseline and difference from placebo in lipidparameters at day 510 in ORION-11

Treatment group LDL-C Total Non-HDL-C Apo-B Lp(a)*cholesterol

Mean baseline 105 185 136 96 107value in mg/dl**

Day 510 (mean percentage change from baseline)

Placebo (n=807) 4 2 2 1 0

Inclisiran (n=810) -46 -28 -41 -38 -19

Difference from -50 -30 -43 -39 -19placebo (LS mean) (-53, -47) (-32, -28) (-46, -41) (-41, -37) (-21, -16)(95% CI)

*At day 540; median percentage change in Lp(a) values

**Mean baseline value in nmol/l for Lp(a)

At day 510, the LDL-C target of <1.8 mmol/l (70 mg/dl) was achieved by 82% of inclisiran patientswith ASCVD compared to 16% of placebo patients. In patients with an ASCVD risk equivalent, the

LDL-C target of <2.6 mmol/l (100 mg/dl) was achieved by 78% of inclisiran patients compared to31% of placebo patients.

Consistent and statistically significant (p<0.05) percentage change in LDL-C from baseline to day 510and time-adjusted percentage change in LDL-C from baseline after day 90 and up to day 540 wasobserved across all subgroups irrespective of baseline demographics, baseline disease characteristics(including gender, age, body mass index, race and baseline statin use), comorbidities, and geographicregions.

ORION-9 was an international, multicentre, double-blind, randomised, placebo-controlled 18-monthtrial in 482 patients with heterozygous familial hypercholesterolaemia (HeFH). All patients weretaking maximally tolerated doses of statins with or without other lipid-modifying therapy, such asezetimibe, and required additional LDL-C reduction. The diagnosis of HeFH was made either bygenotyping or clinical criteria (“definite FH” using either the Simon Broome or WHO/Dutch Lipid

Network criteria).

The co-primary endpoints were the percentage change in LDL-C from baseline to day 510 relative toplacebo, and the time-adjusted percentage change in LDL-C from baseline after day 90 and up today 540 to estimate the integrated effect on LDL-C over time. Key secondary endpoints were theabsolute change in LDL-C from baseline to day 510, the time-adjusted absolute change in LDL-Cfrom baseline after day 90 and up to day 540 and the percentage change from baseline to day 510 in

PCSK9, total cholesterol, Apo-B, and non-HDL-C. Additional secondary endpoints included the,individual responsiveness to inclisiran and the proportion of patients attaining global lipid targets fortheir level of ASCVD risk.

The mean age at baseline was 55 years (range: 21 to 80 years), 22% were ≥65 years old, 53% werewomen, 94% were White, 3% were Black, 3% were Asian and 3% were Hispanic or Latino ethnicity.

The mean baseline LDL-C was 4.0 mmol/l (153 mg/dl). Seventy-four percent (74%) were takinghigh-intensity statins, 15% were taking medium-intensity statins and 10% were not on a statin.

Fifty-two percent (52%) of patients were treated with ezetimibe. The most commonly administeredstatins were atorvastatin and rosuvastatin.

Inclisiran significantly reduced the mean percentage change in LDL-C from baseline to day 510compared to placebo by 48% (95% CI: -54%, -42%; p<0.0001) (Table 4).

Inclisiran also significantly reduced the time-adjusted percentage change in LDL-C from baseline afterday 90 and up to day 540 by 44% compared to placebo (95% CI: -48%, -40%; p<0.0001). Foradditional results, see Table 4.

Table 4 Mean percentage change from baseline and difference from placebo in lipidparameters at day 510 in ORION-9

Treatment group LDL-C Total Non-HDL-C Apo-B Lp(a)*cholesterol

Mean baseline 153 231 180 124 121value in mg/dl**

Day 510 (mean percentage change from baseline)

Placebo (n=240) 8 7 7 3 4

Inclisiran (n=242) -40 -25 -35 -33 -13

Difference from -48 -32 -42 -36 -17placebo (LS mean) (-22, -12)(-54, -42) (-36, -28) (-47, -37) (-40, -32)(95% CI)

*At day 540; median percentage change in Lp(a) values

**Mean baseline value in nmol/l for Lp(a)

At day 510, 52.5% of inclisiran patients with ASCVD achieved their LDL-C target of <1.8 mmol/l(70 mg/dl) compared to 1.4% of placebo patients with ASCVD, while in the group with ASCVD riskequivalents 66.9% of inclisiran patients achieved their LDL-C target of <2.6 mmol/l (100 mg/dl)compared to 8.9% of placebo patients.

Consistent and statistically significant (p<0.05) percentage change in LDL-C from baseline to day 510and time-adjusted percentage change in LDL-C from baseline after day 90 and up to day 540 wereobserved across all subgroups irrespective of baseline demographics, baseline disease characteristics(including gender, age, body mass index, race and baseline statin use), comorbidities, and geographicregions.

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

Following single subcutaneous administration, systemic exposure to inclisiran increasedapproximately dose-proportionally over a range from 24 mg to 756 mg. At the recommended dosingregimen of 284 mg plasma concentrations reached peak in approximately 4 hours post dose, with amean Cmax of 509 ng/ml. Concentrations reached undetectable levels within 48 hours post dosing. Themean area under the plasma concentration-time curve from dosing extrapolated to infinity was7980 ng*h/ml. Pharmacokinetic findings following multiple subcutaneous administrations of inclisiranwere similar to single-dose administration.

Inclisiran is 87% protein bound in vitro at the relevant clinical plasma concentrations. Following asingle subcutaneous 284 mg dose of inclisiran to healthy adults, the apparent volume of distribution isapproximately 500 litres. Based on non-clinical data inclisiran has been shown to have high uptakeinto and selectivity for the liver, the target organ for cholesterol lowering.

Inclisiran is primarily metabolised by nucleases to shorter inactive nucleotides of varying length.

Inclisiran is not a substrate for common drug transporters and, although in vitro studies were notconducted, it is not anticipated to be a substrate for cytochrome P450.

The terminal elimination half-life of inclisiran is approximately 9 hours and no accumulation occurswith multiple dosing. Sixteen percent (16%) of inclisiran is cleared through the kidney.

In the phase I clinical study, an approximately dose proportional increase in inclisiran exposure wasobserved after administration of subcutaneous doses of inclisiran ranging from 24 mg to 756 mg. Noaccumulation and no time-dependent changes were observed after multiple subcutaneous doses ofinclisiran.

In the phase I clinical study, a dissociation was observed between inclisiran pharmacokineticparameters and LDL-C pharmacodynamic effects. Selective delivery of inclisiran to hepatocytes,where it is incorporated into the RNA-induced silencing complex (RISC), results in a long duration ofaction, beyond that anticipated based on the plasma elimination half-life of 9 hours. The maximaleffects of reducing LDL-C were observed with a 284 mg dose, with higher doses not producinggreater effects.

Pharmacokinetic analysis of data from a dedicated renal impairment study reported an increase ininclisiran Cmax of approximately 2.3, 2.0 and 3.3-fold and an increase in inclisiran AUC ofapproximately 1.6, 1.8 and 2.3-fold, in patients with mild (creatinine clearance [CrCL] of 60 ml/min to89 ml/min), moderate (CrCL of 30 ml/min to 59 ml/min) and severe (CrCL of 15 ml/min to29 ml/min) renal impairment, respectively, relative to patients with normal renal function. Despite thehigher transient plasma exposures over 48 hours, the reduction in LDL-C was similar across all groupsof renal function. Based on population pharmacodynamic modelling, no dose adjustment isrecommended in patients with end-stage renal disease. Based on pharmacokinetic, pharmacodynamicand safety assessments, no dose adjustment is necessary in patients with mild, moderate or severerenal impairment. The effect of haemodialysis on inclisiran pharmacokinetics has not been studied.

Considering that inclisiran is eliminated renally, haemodialysis should not be performed for at least72 hours after Leqvio dosing.

Pharmacokinetic analysis of data from a dedicated hepatic impairment study reported an increase ininclisiran Cmax of approximately 1.1 and 2.1-fold, and an increase in inclisiran AUC ofapproximately1.3 and 2.0-fold, respectively, in patients with mild (Child-Pugh class A) and moderate(Child-Pugh class B) hepatic impairment relative to patients with normal hepatic function. Despite thehigher transient inclisiran plasma exposures, the reductions in LDL-C were similar between the groupsof patients administered inclisiran with normal hepatic function and mild hepatic impairment. Inpatients with moderate hepatic impairment baseline PCSK9 levels were markedly lower and thereduction in LDL-C was less than that observed in patients with normal hepatic function. No doseadjustment is necessary in patients with mild to moderate hepatic impairment (Child-Pugh class A and

B). Leqvio has not been studied in patients with severe hepatic impairment (Child-Pugh class C).

A population pharmacodynamic analysis was conducted on data from 4,328 patients. Age, bodyweight, gender, race, and creatinine clearance were not found to significantly influence inclisiranpharmacodynamics. No dose adjustments are recommended for patients with these demographics.

In repeated dose toxicology studies conducted in rats and monkeys the no observed adverse effectlevels (NOAEL) were identified as the highest doses administered subcutaneously which producedexposures considerably in excess of the maximum human exposure. Microscopic observations fromtoxicology studies included vacuolation in hepatocytes of rats and lymph node macrophages ofmonkeys, and the presence of basophilic granules in hepatocytes of monkeys and kidneys of rats andmonkeys. These observations were not associated with changes in clinical laboratory parameters andare not considered adverse.

Inclisiran was not carcinogenic in Sprague-Dawley rats or in TgRasH2 mice administered inclisiran atdoses sufficiently in excess of clinical doses.

No mutagenic or clastogenic potential of inclisiran was found in a battery of tests, including abacterial mutagenicity assay, in vitro chromosomal aberration assay in human peripheral bloodlymphocytes and an in vivo rat bone marrow micronucleus assay.

Reproduction studies performed in rats and rabbits have revealed no evidence of harm to the foetusdue to inclisiran at the highest doses administered, which produced exposure considerably in excess ofthe maximum human exposure.

Inclisiran did not affect the fertility or reproductive performance of male rats and female rats exposedto inclisiran prior to gestation and during gestation. The doses were associated with systemicexposures many times greater than the human exposure at clinical doses.

Inclisiran has been observed in the milk of lactating rats; however, there is no evidence of systemicabsorption in suckling rat neonates.

Water for injections

Sodium hydroxide (for pH adjustment)

Concentrated phosphoric acid (for pH adjustment)

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

3 years

This medicinal product does not require any special storage conditions. Do not freeze.

Pre-filled syringe1.5 ml solution in a pre-filled syringe (Type I glass) with plunger stopper (bromobutyl, fluoroteccoated rubber), with needle and rigid needle shield.

Pack size of one pre-filled syringe.

Pre-filled syringe with needle guard1.5 ml solution in a pre-filled syringe (Type I glass) with plunger stopper (bromobutyl, fluoroteccoated rubber), with needle and rigid needle shield, with needle guard.

Pack size of one pre-filled syringe with needle guard.

Not all pack sizes may be marketed.

Leqvio should be inspected visually prior to administration. The solution should be clear, colourless topale yellow and essentially free of particulates. If the solution contains visible particulate matter, thesolution should not be used.

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

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

EU/1/20/1494/001

EU/1/20/1494/002

09 December 2020

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

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