VYVGART 20mg / ml perfusive solution concentrate medication leaflet

Vyvgart 20 mg/mL concentrate for solution for infusion

Each vial of 20 mL contains 400 mg of efgartigimod alfa (20 mg/mL).

Efgartigimod alfa is a human recombinant immunoglobulin G1 (IgG1)-derived Fc fragment producedin Chinese hamster ovary (CHO) cells by recombinant DNA technology.

Each vial contains 67.2 mg sodium.

For the full list of excipients, see section 6.1.

Concentrate for solution for infusion (sterile concentrate)

Colourless to slightly yellow, clear to slightly opalescent, pH 6.7.

Vyvgart is indicated as an add-on to standard therapy for the treatment of adult patients withgeneralised Myasthenia Gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive.

Efgartigimod alfa must be administered by a healthcare professional and under the supervision of aphysician experienced in the management of patients with neuromuscular disorders.

The recommended dose is 10 mg/kg as a 1-hour intravenous infusion to be administered in cycles ofonce weekly infusions for 4 weeks. Subsequent treatment cycles should be administered according toclinical evaluation. The frequency of treatment cycles may vary by patient (see section 5.1).

In the clinical development program, the earliest time to initiate a subsequent treatment cycle was7 weeks from the initial infusion of the previous cycle. The safety of initiating subsequent cyclessooner than 7 weeks from the start of the previous treatment cycle has not been established.

In patients weighing 120 kg or more, the recommended dose is 1 200 mg (3 vials) per infusion(see section 6.6).

If a scheduled infusion is not possible, treatment may be administered up to 3 days before or after thescheduled time point. Thereafter, the original dosing schedule should be resumed until the treatmentcycle is completed. If a dose needs to be delayed for more than 3 days, the dose should not beadministered to ensure two consecutive doses are given with an interval of at least 3 days.

No dose adjustment is required in patients aged 65 years and older (see section 5.2).

Limited safety and efficacy data in patients with mild renal impairment is available, no doseadjustment is required for patients with mild renal impairment. There is very limited safety andefficacy data in patients with moderate or severe renal impairment (see section 5.2).

No data in patients with hepatic impairment are available. No dose adjustment is required in patientswith hepatic impairment (see section 5.2).

The safety and efficacy of efgartigimod alfa in paediatric population have not yet been established.

No data are available.

This medicinal product should only be administered via intravenous infusion. Do not administer as anintravenous push or bolus injection. It should be diluted with sodium chloride 9 mg/mL (0.9%)solution for injection prior to administration as described in section 6.6.

This medicinal product should be administered over 1 hour. Appropriate treatment for infusion andhypersensitivity-related reactions should be readily available before administration of efgartigimodalfa. In case of infusion reactions, the infusion should be administered at a slower rate, interrupted orcan be discontinued (see section 4.4).

* Inspect the solution visually for particulate matter prior to administration.

* Infuse the total 125 mL of diluted medicinal product over 1 hour using a 0.2 µm filter.

Administer the full amount of solution, flushing the entire line with sodium chloride 9 mg/mL(0.9%) solution for injection at the end.

* Vyvgart should be administered immediately after dilution and the infusion of diluted solutionshould be completed within 4 hours of dilution.

* Chemical and physical in-use stability has been demonstrated for 24 hours at 2 °C to 8 °C. Froma microbiological point of view, unless the method of dilution precludes the risks of microbialcontamination, the product should be used immediately. If not used immediately, in-use storagetimes and conditions are the responsibility of the user. Do not freeze. Allow the dilutedmedicinal product to reach room temperature before administration. Complete the infusionwithin 4 hours of removal from the refrigerator. The diluted medicinal product should not beheated in any other manner than via ambient air.

* Should infusion reactions occur, the infusion should be administered at a slower rate,interrupted or discontinued (see section 4.4).

* Other medicinal products should not be injected into infusion side ports or mixed with Vyvgart.

For instructions on dilution of the medicinal product before administration, see section 6.6.

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.

Myasthenia Gravis Foundation of America (MGFA) Class V patients

Treatment with efgartigimod alfa in patients with MGFA Class V (i.e. myasthenic crisis), defined asintubation with or without mechanical ventilation except in the setting of routine postoperative care,has not been studied. The sequence of therapy initiation between established therapies for MG crisisand efgartigimod alfa, and their potential interactions, should be considered (see section 4.5).

As efgartigimod alfa causes transient reduction in IgG levels the risk of infections may increase(see sections 4.8 and 5.1). The most common infections observed in clinical trials were upperrespiratory tract infections and urinary tract infections (see section 4.8). Patients should be monitoredfor clinical signs and symptoms of infections during treatment with Vyvgart. In patients with an activeinfection, the benefit-risk of maintaining or withholding treatment with efgartigimod alfa should beconsidered until the infection has resolved. If serious infections occur, delaying treatment withefgartigimod alfa should be considered until the infection has resolved.

Infusion reactions and hypersensitivity reactions

Infusion reactions such as rash or pruritus may occur. In the clinical trial, infusion reactions were mildto moderate and did not lead to treatment discontinuation. Patients should be monitored duringadministration and for 1 hour thereafter for clinical signs and symptoms of infusion reactions. Shoulda reaction occur and based on the severity of the reaction the infusion should be administered at aslower rate, interrupted or discontinued and appropriate supportive measures should be instituted.

Once resolved, administration may be cautiously resumed, based on clinical evaluation.

Cases of anaphylactic reaction have been reported in the post-marketing setting. If an anaphylacticreaction is suspected, administration of Vyvgart should be immediately discontinued and appropriatemedical treatment initiated. Patients should be informed of the signs and symptoms of hypersensitivityand anaphylactic reactions and advised to contact their healthcare provider immediately should theyoccur.

All vaccines should be administered according to immunisation guidelines.

The safety of immunisation with live or live-attenuated vaccines and the response to immunisationwith these vaccines during treatment with efgartigimod alfa are unknown. For patients that are beingtreated with efgartigimod alfa, vaccination with live or live-attenuated vaccines is generally notrecommended. If vaccination with live or live-attenuated vaccines is required, these vaccines shouldbe administered at least 4 weeks before treatment and at least 2 weeks after the last dose ofefgartigimod alfa.

Other vaccines may be administered as needed at any time during treatment with efgartigimod alfa.

In the double-blind placebo-controlled study, pre-existing antibodies that bind to efgartigimod alfawere detected in 25/165 (15%) patients with gMG. Treatment-induced antibodies to efgartigimod alfawere detected in 17/83 (21%) patients. In 3 of these 17 patients, treatment-induced anti-drugantibodies (ADAs) persisted until the end of the study. Neutralising antibodies were detected in6/83 (7%) of patients treated with Vyvgart, including the 3 patients with persisting treatment-induced

ADAs. Retreatment did not cause an increase in incidence or titres of efgartigimod alfa antibodies.

There was no apparent impact of antibodies to efgartigimod alfa on clinical efficacy or safety, nor onpharmacokinetics and pharmacodynamic parameters.

When non-steroidal immunosuppressants, corticosteroids and anticholinesterase therapies aredecreased or discontinued, patients should be monitored closely for signs of disease exacerbation.

This medicinal product contains 67.2 mg sodium per vial, equivalent to 3.4% of the WHOrecommended maximum daily intake of 2 g sodium for an adult. This medicinal product will befurther prepared for administration with sodium-containing solution (see section 6.6) and this shouldbe considered in relation to the total sodium intake to the patient from all sources per day.

Polysorbates

This medicinal product contains 4.1 mg of polysorbate 80 in each vial which is equivalent to0.2 mg/mL. Polysorbates may cause allergic reactions.

No interaction studies have been performed.

Efgartigimod alfa may decrease concentrations of compounds that bind to the human neonatal Fc

Receptor (FcRn), i.e., immunoglobulin products, monoclonal antibodies, or antibody derivativescontaining the human Fc domain of the IgG subclass. If possible, it is recommended to postponeinitiation of treatment with these products to 2 weeks after the last dose of any given treatment cycleof Vyvgart. As a precaution, patients receiving Vyvgart while on treatment with these products shouldbe closely monitored for the intended efficacy response of those products.

Plasma exchange, immunoadsorption, and plasmapheresis may reduce circulating levels ofefgartigimod alfa.

All vaccines should be administered according to immunisation guidelines.

The potential interaction with vaccines was studied in a nonclinical model using Keyhole limpethemocyanin (KLH) as the antigen. The weekly administration of 100 mg/kg to monkeys did notimpact the immune response to KLH immunisation.

For patients that are being treated with efgartigimod alfa, vaccination with live or live-attenuatedvaccines is generally not recommended. If vaccination with live or live-attenuated vaccines isrequired, these vaccines should be administered at least 4 weeks before treatment and at least 2 weeksafter the last dose of a treatment cycle efgartigimod alfa (see section 4.4).

There is no available data on the use of efgartigimod alfa during pregnancy. Antibodies includingtherapeutic monoclonal antibodies are known to be actively transported across the placenta (after30 weeks of gestation) by binding to the FcRn.

Efgartigimod alfa may be transmitted from the mother to the developing foetus. As efgartigimod alfais expected to reduce maternal antibody levels, and is also expected to inhibit the transfer of maternalantibodies to the foetus, reduction in passive protection to the newborn is anticipated. Therefore, risksand benefits of administering live/live-attenuated vaccines to infants exposed to efgartigimod alfain utero should be considered (see section 4.4).

Treatment of pregnant women with Vyvgart should only be considered if the clinical benefitoutweighs the risks.

There is no information regarding the presence of efgartigimod alfa in human milk, the effects on thebreastfed child or the effects on milk production. Animal studies on the transfer of efgartigimod alfainto milk have not been conducted, and therefore, excretion into maternal milk cannot be excluded.

Maternal IgG is known to be present in human milk. Treatment of lactating women with efgartigimodalfa should only be considered if the clinical benefit outweighs the risks.

There is no available data on the effect of efgartigimod alfa on fertility in humans. Animal studiesshowed no impact of efgartigimod alfa on male and female fertility parameters (see section 5.3).

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

The most frequently observed adverse reactions were upper respiratory tract infections and urinary tractinfections (10.7% and 9.5%, respectively).

The safety of Vyvgart was evaluated in 167 patients with gMG in the Phase 3 double-blindplacebo-controlled clinical study.

Adverse reactions are listed in Table 1 by system organ class and preferred term. Frequency categoriesare defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100)or rare (≥ 1/10 000 to < 1/1 000). Within each frequency grouping, adverse reactions are presented inorder of decreasing seriousness.

Table 1. Adverse reactions

System organ class Adverse reaction Frequency category

Infections and infestations* Upper respiratory tract infections Very common

Urinary tract infections Common

Bronchitis Common

Immune system disorders Anaphylactic reaction a Not known

System organ class Adverse reaction Frequency category

Gastrointestinal disorders Nausea a Common

Musculoskeletal and

Myalgia Commonconnective tissue disorders

Injury, poisoning and

* Procedural headache Commonprocedural complications

* See paragraph “Description of selected adverse reactions”a From spontaneous post-marketing reporting

The most frequently reported adverse reactions were infections, and the most reported infections wereupper respiratory tract infections (10.7% [n = 9] of patients treated with efgartigimod alfa and 4.8%[n = 4] of patients treated with placebo) and urinary tract infections (9.5% [n = 8] of patients treatedwith efgartigimod alfa and 4.8% [n = 4] of patients treated with placebo). These infections were mildto moderate in severity in patients who received efgartigimod alfa (≤ Grade 2 according to the

Common Terminology Criteria for Adverse Events). Overall, treatment emergent infections werereported in 46.4% (n = 39) of patients treated with efgartigimod alfa and 37.3% (n = 31) of patientstreated with placebo. The median time from treatment initiation to emergence of infections was6 weeks. Incidence of infections did not increase with subsequent treatment cycles. Treatmentdiscontinuation or temporary interruption of treatment due to an infection occurred in less than 2% ofpatients.

Procedural headache

Procedural headache was reported in 4.8% of the patients treated with efgartigimod alfa and 1.2% ofpatients treated with placebo. Procedural headache was reported when a headache was judged to betemporally related to the intravenous infusion of efgartigimod alfa. All were mild or moderate exceptone event which was reported as severe (Grade 3).

All other adverse reactions were mild or moderate with the exception of one case of myalgia (Grade 3).

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. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

There are no known specific signs and symptoms of overdose with efgartigimod alfa. In the event ofan overdose the adverse events that may occur are not expected to be different from those that may beobserved at the recommended dose. Patients should be monitored for adverse reactions, andappropriate symptomatic and supportive treatment initiated. There is no specific antidote for overdosewith efgartigimod alfa.

Pharmacotherapeutic group: Immunosuppressants, selective immunosuppressants, ATC code:

L04AA58

Efgartigimod alfa is a human IgG1 antibody fragment engineered for increased affinity to the neonatal

Fc Receptor (FcRn). Efgartigimod alfa binds to FcRn, resulting in a reduction in the levels ofcirculating IgG including pathogenic IgG autoantibodies. Efgartigimod alfa does not affect the levelsof other immunoglobulins (IgA, IgD, IgE or IgM), and does not reduce those of albumin.

IgG autoantibodies are the underlying cause of the pathogenesis of MG. They impair neuromusculartransmission by binding to acetylcholine receptors (AChR), muscle-specific tyrosine kinase (MuSK)or low-density lipoprotein receptor-related protein 4 (LRP4).

In a double-blind placebo-controlled study in gMG patients, efgartigimod alfa decreased serum IgGlevels and AchR autoantibody levels at the recommended dose and schedule (see section 4.2).

Maximum mean percentage decrease in total IgG levels compared to baseline reached 61% one weekafter the last infusion of the initial treatment cycle and returned to baseline levels 9 weeks after the lastinfusion. Similar effects were also observed for all subtypes of IgG. Decrease in AchR autoantibodylevels followed a similar time course with maximum mean percentage decrease of 58% one week afterthe last infusion and return to baseline levels 7 weeks after the last infusion. Similar changes wereobserved during the second cycle of the study.

Efficacy of efgartigimod alfa for the treatment of adults with generalised Myasthenia Gravis (gMG)was studied in a 26-week, multicentre randomised double-blind placebo-controlled trial(ARGX-113-1704).

In this study, patients had to meet the following main criteria at screening:

* Myasthenia Gravis Foundation of America (MGFA) clinical classification class II, III or IV;

* Patients with either positive or negative serologic tests for antibodies to AchR;

* MG-Activities of Daily Living (MG-ADL) total score of ≥ 5;

* On stable doses of MG therapy prior to screening, that included acetylcholinesterase (AchE)inhibitors, steroids or non-steroidal immunosuppressive therapy (NSIST), either in combinationor alone [NSISTs included but were not limited to azathioprine, methotrexate, cyclosporine,tacrolimus, mycophenolate mofetil, and cyclophosphamide];

* IgG levels of at least 6 g/L.

Patients with MGFA Class V gMG; patients with documented lack of clinical response to PLEX;patients treated with PLEX, IVIg one month and monoclonal antibodies six months prior to startingtreatment; and patients with active (acute or chronic) hepatitis B infection, hepatitis C seropositivity,and diagnosis of AIDS, were excluded from the trials.

A total of 167 patients were enrolled in the study and were randomised to either efgartigimod alfaintravenous (n = 84) or placebo (n = 83). Baseline characteristics were similar between treatmentgroups, including median age at diagnosis [45 (19-81) years], gender [most were female; 75%(efgartigimod alfa) versus 66% (placebo)], race [most patients were white; 84.4%] and median timesince diagnosis [8.2 years (efgartigimod alfa) and 6.9 years (placebo)].

The majority of patients (77% in each group) tested positive for antibodies to aChR (aChR-Ab) and23% of patients tested negative for aChR-Ab.

During the study, over 80% of patients in each group received aChE inhibitors, over 70% in eachtreatment group received steroids, and approximately 60% in each treatment group received NSISTs,at stable doses. At study entry, approximately 30% of patients in each treatment group had no previousexposure to NSISTs.

Median MG-ADL total score was 9.0 in both treatment groups, and median Quantitative Myasthenia

Gravis (QMG) total score was 17 and 16 in the efgartigimod alfa and placebo groups, respectively.

Patients were treated with efgartigimod alfa intravenous 10 mg/kg administered once weekly for4 weeks and received a maximum of 3 treatment cycles (see section 4.2).

The efficacy of efgartigimod alfa was measured using the Myasthenia Gravis-Specific Activities of

Daily Living scale (MG-ADL) which assesses the impact of gMG on daily functions. A total scoreranges from 0 to 24 with the higher scores indicating more impairment. In this study, an MG-ADLresponder was a patient with ≥ 2-point reduction in the total MG-ADL score compared to the treatmentcycle baseline, for at least 4 consecutive weeks with the first reduction occurring no later than 1 weekafter the last infusion of the cycle.

The efficacy of efgartigimod alfa was also measured using the QMG total score which is a gradingsystem that assesses muscle weakness with a total possible score of 0 to 39 where higher scoresindicate more severe impairment. In this study, a QMG responder was a patient who had a ≥ 3-pointreduction in the total QMG score compared to the treatment cycle baseline, for at least 4 consecutiveweeks with the first reduction occurring no later than 1 week after last infusion of the cycle.

The primary efficacy endpoint was the comparison of the percentage of MG-ADL responders duringthe first treatment cycle (C1) between treatment groups in the aChR-Ab seropositive population.

A key secondary endpoint was the comparison of the percentage of QMG responders during C1between both treatment groups in the aChR-Ab seropositive patients.

Table 2. MG-ADL and QMG responders during cycle 1 in aChR-Ab seropositive population(mITT analysis set)

Population Efgartigimod alfa Placebo P-value Differencen/N (%) n/N (%) Efgartigimod alfa-

Placebo (95% CI)

MG-ADL aChR-Ab seropositive 44/65 (67.7) 19/64 (29.7) < 0.0001 38.0 (22.1; 54.0)

QMG aChR-Ab seropositive 41/65 (63.1) 9/64 (14.1) < 0.0001 49.0 (34.5; 63.5)aChR-Ab = acetylcholine receptor-antibody; MG-ADL = Myasthenia Gravis Activities of Daily Living;

QMG = Quantitative Myasthenia Gravis; mITT = modified intent-to-treat; n = number of patients for whom theobservation was reported; N = number of patients in the analysis set; CI = confidence interval;

Logistic regression stratified for aChR-Ab status (if applicable), Japanese/Non-Japanese and standard of care,with baseline MG-ADL as covariate/QMG as covariates

Two-sided exact p-value

Analyses show that during the second treatment cycle MG-ADL responder rates were similar to thoseduring the first treatment cycle (see Table 3).

Table 3. MG-ADL and QMG responders during cycle 2 in aChR-Ab seropositive population(mITT analysis set)

Population Efgartigimod alfa Placebon/N (%) n/N (%)

MG-ADL aChR-Ab seropositive 36/51 (70.6) 11/43 (25.6)

QMG AChR-Ab seropositive 24/51 (47.1) 5/43 (11.6)

AChR-Ab = acetylcholine receptor-antibody; MG-ADL = Myasthenia Gravis Activities of Daily Living;

QMG = Quantitative Myasthenia Gravis; mITT = modified intent-to-treat; n = number of patients for whom theobservation was reported; N = number of patients in the analysis set.

Exploratory data shows that onset of response was observed within 2 weeks of initial infusion in 37/44(84%) patients treated with efgartigimod alfa intravenous in the AChR-Ab seropositive MG-ADLresponders.

In the double-blind placebo-controlled study, the earliest possible time to initiating the subsequenttreatment cycle was 8 weeks after the initial infusion of the first treatment cycle. In the overallpopulation the mean time to the second treatment cycle in the efgartigimod alfa intravenous group was13 weeks (SD 5.5 weeks) and the median time was 10 weeks (8-26 weeks) from the initial infusion ofthe first treatment cycle. In the open-label extension study the earliest possible time of initiation of thesubsequent treatment cycles was 7 weeks.

In patients that responded to treatment, the duration of clinical improvement was 5 weeks in5/44 (11%) patients, 6-7 weeks in 14/44 (32%) of patients, 8-11 weeks in 10/44 (23%) patients and12 weeks or more in 15/44 (34%) patients.

Based upon population PK data analysis in healthy subjects and patients the volume of distribution is18 L.

Efgartigimod alfa is expected to be degraded by proteolytic enzymes into small peptides andamino acids.

The terminal half-life is 80 to 120 hours (3 to 5 days). Based upon population PK data analysis, theclearance is 0.128 L/h. The molecular weight of efgartigimod alfa is approximately 54 kDa, which isat the boundary of molecules that are renally filtered.

The pharmacokinetics profile of efgartigimod alfa is linear, independent of dose or time, withnegligible accumulation. The geometric mean accumulation ratio based on observed peakconcentrations was 1.12.

Age, gender, race and bodyweight

The pharmacokinetics of efgartigimod alfa were not affected by age (19-78 years), gender and race.

A population pharmacokinetic analysis showed that the effect of bodyweight on efgartigimod alfaexposure was limited at a dose of 10 mg/kg in patients up to 120 kg as well as in patients of 120 kgand above who received a capped dose of 1 200 mg/infusion. There was no effect of bodyweight onthe extent of IgG reduction. In the double-blind placebo-controlled study, 5 (3%) patients were over120 kg. The median bodyweight of patients on efgartigimod alfa in the study was 76.5 kg (min 49;max 229).

No dedicated pharmacokinetic studies have been performed in patients with renal impairment.

The effect of renal function marker estimated glomerular filtration rate [eGFR] as a covariate in apopulation pharmacokinetic analysis showed a reduced clearance resulting in a limited increase inexposure in patients with mild renal impairment (eGFR 60-89 mL/min/1.73 m2). No specific doseadjustment is recommended in patients with mild renal impairment.

There is insufficient data on the impact of moderate renal impairment (eGFR 30-59 mL/min/1.73 m2)and severe renal impairment (eGFR < 30 mL/min/1.73 m2) on efgartigimod alfa pharmacokineticparameters.

No dedicated pharmacokinetic study has been performed in patients with hepatic impairment.

The effect of hepatic function markers as covariates in a population pharmacokinetic analysis did notshow any impact on the pharmacokinetics of efgartigimod alfa.

Non-clinical data reveal no special hazard for humans based on conventional studies of safetypharmacology and repeated dose toxicity.

In reproduction studies in rats and rabbits, intravenous administration of efgartigimod alfa did notresult in adverse effects on fertility and pregnancy nor were teratogenic effects observed up to doselevels corresponding to 11-fold (rats) and 56-fold (rabbits) to the exposure (AUC) at the maximumrecommended therapeutic dose.

Carcinogenicity and genotoxicity

No studies have been conducted to assess the carcinogenic and genotoxic potential ofefgartigimod alfa.

Sodium dihydrogen phosphate, monohydrate

Disodium hydrogen phosphate, anhydrous

Sodium chloride

Arginine hydrochloride

Polysorbate 80 (E433)

Water for injections

This medicinal product must not be mixed with other medicinal products except those mentioned insection 6.6.

3 years

Chemical and physical in-use stability has been demonstrated for 24 hours at 2 °C to 8 °C.

From a microbiological point of view, unless the method of dilution precludes the risks of microbialcontamination, the product should be used immediately. If not used immediately, in-use storage timesand conditions are the responsibility of the user.

Store in a refrigerator (2 °C - 8 °C).

Do not freeze.

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

For storage conditions after dilution of the medicinal product, see section 6.3.

Concentrate in single-dose 20 mL glass vials (Type I) with rubber stopper (butyl, siliconised),aluminium seal and polypropylene flip-off cap.

Pack size of 1 vial.

The efgartigimod alfa solution diluted in sodium chloride 9 mg/mL (0.9%) solution for injection canbe administered using polyethylene (PE), polyvinyl chloride (PVC), ethylene vinyl acetate (EVA) andethylene/polypropylene copolymer bags (polyolefins bags), as well as with PE, PVC andpolyurethane/polypropylene infusion lines, together with polyurethane (PUR) or PVC filters withpolyethersulfone (PES) or polyvinylidene fluoride (PVDF) filter membrane.

Using the formula in the table below, calculate the following:

* The dose of Vyvgart required based on the patient’s bodyweight at the recommended dose of10 mg/kg. For patients weighing over 120 kg use a bodyweight of 120 kg to calculate the dose.

The maximum total dose per infusion is 1 200 mg. Each vial contains 400 mg of efgartigimodalfa at a concentration of 20 mg/mL.

* The number of vials needed.

* The volume of sodium chloride 9 mg/mL (0.9%) solution for injection. The total volume ofdiluted medicinal product is 125 mL.

Table 4. Formula

Step 1 - Calculate the dose (mg) 10 mg/kg x weight (kg)

Step 2 - Calculate the volume of concentrate (mL) dose (mg) ÷ 20 mg/mL

Step 3 - Calculate the number vials volume of concentrate (mL) ÷ 20 mL

Step 4 - Calculate the volume of sodium chloride 9 mg/mL 125 mL - concentrate volume (mL)(0.9%) solution for injection (mL)

* Visually inspect that the vial content is clear to slightly opalescent, colourless to slightly yellow,and devoid of particulate matter. If visible particles are observed and/or the liquid in the vial isdiscoloured, the vial must not be used. Do not shake the vials.

* Using aseptic technique throughout the preparation of the diluted solution:

- Gently withdraw the required amount of Vyvgart from the appropriate number of vialswith a sterile syringe and needle (see Table 4). Discard any unused portion of the vials.

- Transfer the calculated dose of the product into an infusion bag.

- Dilute the withdrawn product by adding the calculated amount of sodium chloride9 mg/mL (0.9%) solution for injection to make a total volume of 125 mL.

- Gently invert the infusion bag containing the diluted product without shaking to ensurethorough mixing of the product and the diluent.

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

argenx BV

Industriepark-Zwijnaarde 79052 Gent

Belgium

EU/1/22/1674/001

Date of first authorisation: 10 August 2022

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

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