PONVORY 20mg tablets medication leaflet

Ponvory 2 mg film-coated tablets

Ponvory 3 mg film-coated tablets

Ponvory 4 mg film-coated tablets

Ponvory 5 mg film-coated tablets

Ponvory 6 mg film-coated tablets

Ponvory 7 mg film-coated tablets

Ponvory 8 mg film-coated tablets

Ponvory 9 mg film-coated tablets

Ponvory 10 mg film-coated tablets

Ponvory 20 mg film-coated tablets

Ponvory 2 mg film-coated tablets

Each film-coated tablet contains 2 mg of ponesimod

Each tablet contains 23 mg of lactose.

Ponvory 3 mg film-coated tablets

Each film-coated tablet contains 3 mg of ponesimod

Each tablet contains 22 mg of lactose.

Ponvory 4 mg film-coated tablets

Each film-coated tablet contains 4 mg of ponesimod

Each tablet contains 21 mg of lactose.

Ponvory 5 mg film-coated tablets

Each film-coated tablet contains 5 mg of ponesimod

Each tablet contains 118 mg of lactose.

Ponvory 6 mg film-coated tablets

Each film-coated tablet contains 6 mg of ponesimod

Each tablet contains 117 mg of lactose.

Ponvory 7 mg film-coated tablets

Each film-coated tablet contains 7 mg of ponesimod

Each tablet contains 117 mg of lactose.

Ponvory 8 mg film-coated tablets

Each film-coated tablet contains 8 mg of ponesimod

Each tablet contains 116 mg of lactose.

Ponvory 9 mg film-coated tablets

Each film-coated tablet contains 9 mg of ponesimod

Each tablet contains 115 mg of lactose.

Ponvory 10 mg film-coated tablets

Each film-coated tablet contains 10 mg of ponesimod

Each tablet contains 114 mg of lactose.

Ponvory 20 mg film-coated tablets

Each film-coated tablet contains 20 mg of ponesimod

Each tablet contains 104 mg of lactose.

For the full list of excipients, see section 6.1.

Film-coated tablet (tablet)

Ponvory 2 mg film-coated tablets

White, round, biconvex, film-coated tablet of 5 mm diameter with “2” on one side and an arch on theother side.

Ponvory 3 mg film-coated tablets

Red, round, biconvex, film-coated tablet of 5 mm diameter with “3” on one side and an arch on theother side.

Ponvory 4 mg film-coated tablets

Purple, round, biconvex, film-coated tablet of 5 mm diameter with “4” on one side and an arch on theother side.

Ponvory 5 mg film-coated tablets

Green, round, biconvex, film-coated tablet of 8.6 mm diameter with “5” on one side and an arch andan “A” on the other side.

Ponvory 6 mg film-coated tablets

White, round, biconvex, film-coated tablet of 8.6 mm diameter with “6” on one side and an arch andan “A” on the other side.

Ponvory 7 mg film-coated tablets

Red, round, biconvex, film-coated tablet of 8.6 mm diameter with “7” on one side and an arch and an“A” on the other side.

Ponvory 8 mg film-coated tablets

Purple, round, biconvex, film-coated tablet of 8.6 mm diameter with “8” on one side and an arch andan “A” on the other side.

Ponvory 9 mg film-coated tablets

Brown, round, biconvex, film-coated tablet of 8.6 mm diameter with “9” on one side and an arch andan “A” on the other side.

Ponvory 10 mg film-coated tablets

Orange, round, biconvex, film-coated tablet of 8.6 mm diameter with “10” on one side and an arch andan “A” on the other side.

Ponvory 20 mg film-coated tablets

Yellow, round, biconvex, film-coated tablet of 8.6 mm diameter with “20” on one side and an arch andan “A” on the other side.

Ponvory is indicated for the treatment of adult patients with relapsing forms of multiple sclerosis(RMS) with active disease defined by clinical or imaging features.

Treatment should be initiated under the supervision of a physician experienced in the management ofmultiple sclerosis.

Treatment initiation

Treatment must be started with the 14-day treatment initiation pack (see section 6.5). Treatment startswith one 2 mg tablet orally once daily on day 1 and dose-escalation progresses with the titrationschedule outlined in Table 1.

Table 1: Dose titration regimen

Titration day Daily dose

Day 1 and 2 2 mg

Day 3 and 4 3 mg

Day 5 and 6 4 mg

Day 7 5 mg

Day 8 6 mg

Day 9 7 mg

Day 10 8 mg

Day 11 9 mg

Day 12, 13 and 14 10 mg

If dose titration is interrupted, missed dose instructions must be followed (see also section 4.2,“Re-initiation of therapy following treatment interruption during dose titration or maintenanceperiod”).

After dose titration is complete (see also section 4.2, Treatment initiation), the recommendedmaintenance dose of Ponvory is one 20 mg tablet taken orally once daily.

Re-initiation of therapy following treatment interruption during dose titration or maintenance period

- if less than 4 consecutive doses are missed, resume treatment with the first missed dose.

- if 4 or more consecutive doses are missed, reinitiate treatment with day 1 (2 mg) of the titrationregimen (new treatment initiation pack).

The same first dose monitoring as for treatment initiation is recommended when 4 or moreconsecutive doses of ponesimod are missed during the titration or maintenance periods.

Clinical studies of ponesimod did not include patients aged 65 years and older. Ponesimod should beprescribed with caution in patients aged 65 years and over due to the lack of data on safety andefficacy.

Based on clinical pharmacology studies, no dose adjustment is needed in patients with mild to severerenal impairment (see section 5.2).

No dose adjustment is necessary in patients with mild hepatic impairment (Child-Pugh class A) (seesection 5.2).

Ponvory is contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh class

B and C, respectively) (see sections pct. 4.3, pct. 5.2).

The safety and efficacy of Ponvory in children and adolescents aged less than 18 years have not beenestablished. No data are available.

Ponesimod should be administered orally once daily. Ponesimod can be taken with or without food(see section 5.2).

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

- Immunodeficient state (see section 4.4).

- Patients who in the last 6 months experienced myocardial infarction, unstable angina, stroke,transient ischaemic attack (TIA), decompensated heart failure requiring hospitalisation, or New

York Heart Association (NYHA) Class III or IV heart failure.

- Patients who have presence of Mobitz type II second-degree, third-degree atrioventricular (AV)block, or sick sinus syndrome, unless patient has a functioning pacemaker (see section 4.4).

- Severe active infections, active chronic infections.

- Active malignancies.

- Moderate or severe hepatic impairment (Child-Pugh class B and C, respectively).

- During pregnancy and in women of childbearing potential not using effective contraception (seesection 4.6).

Bradyarrhythmia

Initiation of treatment with ponesimod

Prior to treatment initiation with ponesimod, an electrocardiogram (ECG) in all patients should beobtained to determine whether pre-existing conduction abnormalities are present. In patients withcertain pre-existing conditions, first-dose monitoring is recommended (see below).

Initiation of ponesimod treatment may result in a transient decrease in heart rate (HR) and AVconduction delays (see sections 4.8 and 5.1), therefore an up-titration scheme must be used to reachthe maintenance dose of ponesimod (20 mg) (see section 4.2).

After the first dose of ponesimod, the decrease in HR typically begins within an hour and reaches itsnadir within 2-4 hours. The HR typically recovers to baseline levels 4-5 hours after administration.

The mean decrease in HR on day 1 of dosing (2 mg) was 6 bpm. With up-titration after day 1, thedecrease in HR is less pronounced with no further post-dose decrease in HR observed after day 3.

Caution should be applied when ponesimod is initiated in patients receiving treatment with abeta-blocker because of the additive effects on lowering heart rate; temporary interruption of thebeta-blocker treatment may be needed prior to initiation of ponesimod (see section below andsection 4.5).

For patients receiving a stable dose of a beta-blocker, the resting HR should be considered beforeintroducing ponesimod treatment. If the resting HR is greater than 55 bpm under chronic beta-blockertreatment, ponesimod can be introduced. If resting HR is less than or equal to 55 bpm, beta-blockertreatment should be interrupted until the baseline HR is greater than 55 bpm. Treatment withponesimod can then be initiated and treatment with a beta-blocker can be reinitiated after ponesimodhas been up-titrated to the target maintenance dose (see section 4.5). Beta-blocker treatment can beinitiated in patients receiving stable doses of ponesimod.

First dose monitoring in patients with certain pre-existing cardiac conditions

Because initiation of ponesimod treatment may result in a decrease in HR, first-dose 4-hourmonitoring is recommended for patients with sinus bradycardia [HR less than 55 beats per minute(bpm)], first- or second-degree [Mobitz type I] AV block, or a history of myocardial infarction or heartfailure occurring more than 6 months prior to treatment initiation and in stable condition (seesection 5.1).

Administer the first dose of ponesimod in a setting where resources to appropriately managesymptomatic bradycardia are available. Monitor patients for 4 hours after the first dose for signs andsymptoms of bradycardia with a minimum of hourly pulse and blood pressure measurements. Obtainan ECG in these patients at the end of the 4-hour observation period.

Additional monitoring after 4-hours is recommended if any of the following abnormalities are present(even in the absence of symptoms), continue monitoring until the abnormality resolves:

- HR 4 hours postdose is less than 45 bpm

- HR 4 hours postdose is at the lowest value postdose, suggesting that the maximumpharmacodynamic effect on the heart may not have occurred

- The ECG 4 hours postdose shows new onset second-degree or higher AV block

If postdose symptomatic bradycardia, bradyarrhythmia, or conduction related symptoms occur, or if

ECG 4 hours post-dose shows new onset second degree or higher AV block or QTc greater than orequal to 500 msec, initiate appropriate management, begin continuous ECG monitoring, and continuemonitoring until the symptoms have resolved if no pharmacological treatment is required. Ifpharmacological treatment is required, continue monitoring overnight and repeat 4-hour monitoringafter the second dose.

Cardiologist advice should be obtained before initiation of ponesimod in the following patients todetermine overall benefit risk and the most appropriate monitoring strategy

- In patients with significant QT prolongation (QTc greater than 500 msec) or who are alreadybeing treated with QT-prolonging medicinal products with known arrhythmogenic properties(risk of torsades de pointes)

- In patients with atrial flutter/fibrillation or arrhythmias treated with Class Ia (e.g., quinidine,procainamide) or Class III (e.g., amiodarone, sotalol) anti-arrhythmic medicinal products (seesection 4.5)

- In patients with unstable ischaemic heart disease, cardiac decompensated failure occurring morethan 6 months prior to treatment initiation, history of cardiac arrest, cerebrovascular disease(TIA, stroke occurring more than 6 months prior to treatment initiation), and uncontrolledhypertension, since significant bradycardia may be poorly tolerated in these patients, treatmentis not recommended

- In patients with a history of Mobitz Type II second degree AV block or higher-grade AV block,sick-sinus syndrome, or sino-atrial heart block (see section 4.3)

- In patients with a history of recurrent syncope or symptomatic bradycardia

- In patients receiving concurrent therapy with drugs that decrease heart rate (e.g., beta-blockers,non-dihydropyridine calcium channel blockers - diltiazem and verapamil, and other drugs thatmay decrease HR such as digoxin) (see above and section 4.5), consider potential need to switchto non-HR lowering medicinal products. Concomitant use of these medicinal products duringponesimod initiation may be associated with severe bradycardia and heart block.

Risk of infections

Ponesimod causes a dose-dependent reduction in peripheral lymphocyte count to 30-40% of baselinevalues due to reversible sequestration of lymphocytes in lymphoid tissues. Ponesimod may thereforeincrease the risk of infections (see section 4.8). Life-threatening and rare fatal infections have beenreported in association with sphingosine 1-phosphate (S1P) receptor modulators.

Before initiating treatment with ponesimod, results from a recent complete blood count (CBC) withdifferential (including lymphocyte count) (i.e., within 6 months or after discontinuation of priortherapy) should be reviewed. Assessments of CBC are also recommended periodically duringtreatment. Absolute lymphocyte counts <0.2 × 109/L, if confirmed, should lead to interruption ofponesimod therapy until the level reaches >0.8 × 109/L when re-initiation of ponesimod can beconsidered.

Initiation of treatment with ponesimod should be delayed in patients with severe active infection untilresolution.

Effective diagnostic and therapeutic strategies should be employed in patients with symptoms ofinfection while on therapy. Suspension of treatment with ponesimod should be considered if a patientdevelops a serious infection.

In the development program, pharmacodynamic effects, such as lowering effects on peripherallymphocyte count, were restored to normal within 1 week after discontinuation of ponesimod. In the

OPTIMUM study, peripheral lymphocyte counts were restored to normal within 2 weeks afterdiscontinuation of ponesimod, which was the first timepoint evaluated. Vigilance for signs andsymptoms of infection should be continued for 1-2 weeks after ponesimod is discontinued (see belowand section 4.8).

Herpes viral infections

Cases of herpes viral infection have been reported in the development program of ponesimod (seesection 4.8).

Patients without a healthcare professional confirmed history of varicella (chickenpox) or withoutdocumentation of a full course of vaccination against varicella zoster virus (VZV) should be tested forantibodies to VZV before initiating treatment. A full course of vaccination for antibody-negativepatients with varicella vaccine is recommended prior to commencing treatment with ponesimod. Thetreatment with ponesimod should be delayed for 4 weeks after vaccination to allow the full effect ofvaccination to occur. See Vaccinations section below.

Cryptococcal infections

Cases of fatal cryptococcal meningitis (CM) and disseminated cryptococcal infections have beenreported with other S1P receptor modulators. No cases of CM have been reported inponesimod-treated patients in the development program. Physicians should be vigilant for clinicalsymptoms or signs of CM. Patients with symptoms or signs consistent with a cryptococcal infectionshould undergo prompt diagnostic evaluation and treatment. Ponesimod treatment should besuspended until a cryptococcal infection has been excluded. If CM is diagnosed, appropriate treatmentshould be initiated.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral infection of the braincaused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, andthat usually leads to death or severe disability. Typical symptoms associated with PML are diverse,progress over days to weeks, and include progressive weakness on one side of the body or clumsinessof limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusionand personality changes.

No cases of PML or PML-IRIS (Immune reconstitution inflammatory syndrome) have been reportedin ponesimod-treated patients in the development program; however, PML or PML-IRIS have beenreported in patients treated with S1P receptor modulators and other multiple sclerosis (MS) therapiesand have been associated with some risk factors (e.g., immunocompromised patients, polytherapy withimmunosuppressants).

Physicians should be vigilant for clinical symptoms or magnetic resonance imaging (MRI) findingsthat may be suggestive of PML. MRI findings may be apparent before clinical signs or symptoms. If

PML is suspected, treatment with ponesimod should be suspended until PML has been excluded. Ifconfirmed, treatment with ponesimod should be discontinued.

IRIS has been reported in patients treated with S1P receptor modulators who developed PML andsubsequently discontinued treatment. IRIS presents as a clinical decline in the patient’s condition thatmay be rapid, can lead to serious neurological complications or death, and is often associated withcharacteristic changes on MRI. The time to onset of IRIS in patients with PML was generally withinfour months after S1P receptor modulator discontinuation. Monitoring for development of IRIS andappropriate treatment of the associated inflammation should be undertaken.

Prior and concomitant treatment with anti-neoplastic, immune-modulating, or immunosuppressivetherapies

In patients that are taking anti-neoplastic, immune-modulating, or immunosuppressive therapies(including corticosteroids), or if there is a history of prior use of these medicinal products, possibleunintended additive immune system effects should be considered before initiating treatment withponesimod (see section 4.5).

When switching from medicinal products with prolonged immune effects, the half-life and mode ofaction of these medicinal products must be considered in order to avoid unintended additive effects onthe immune system while at the same time minimising risk of disease reactivation, when initiatingponesimod.

Pharmacokinetic/pharmacodynamic modelling indicates lymphocyte counts returned to the normalrange in >90% of healthy subjects within 1 week of stopping ponesimod therapy (see section 5.1). Inthe development program, pharmacodynamic effects, such as lowering of peripheral lymphocytecounts, were restored to normal within 1 week after the last dose.

Use of immunosuppressants may lead to an additive effect on the immune system, and thereforecaution should be applied up to 1 week after the last dose of ponesimod (see section 4.5).

No clinical data are available on the efficacy and safety of vaccinations in patients taking ponesimod.

Vaccinations may be less effective if administered during ponesimod treatment.

Avoid the use of live attenuated vaccines while patients are taking ponesimod. If the use of liveattenuated vaccine immunisation is required, ponesimod treatment should be paused from 1 week priorto 4 weeks after a planned vaccination (see section 4.5).

Macular oedema

Ponesimod increases the risk of macular oedema (see section 4.8). An ophthalmic evaluation of thefundus, including the macula, is recommended in all patients before starting treatment and again at anytime if a patient reports any change in vision while on ponesimod therapy.

In the clinical trial experience in patients with all doses of ponesimod, the rate of macular oedema was0.7%, the majority of patients had pre-existing risk factors or comorbid conditions. Most casesoccurred within the first 6 months of therapy.

Ponesimod therapy should not be initiated in patients with macular oedema until resolution.

Continuation of ponesimod therapy in patients with macular oedema has not been evaluated. Patientswho present with visual symptoms of macular oedema should be evaluated and, if confirmed,treatment with ponesimod should be discontinued. A decision on whether ponesimod should bere-initiated after resolution needs to take into account the potential benefits and risks for the individualpatient.

Macular oedema in patients with a history of uveitis or diabetes mellitus

Patients with a history of uveitis and patients with diabetes mellitus are at increased risk of macularoedema during therapy with S1P receptor modulators. Therefore, these patients should have regularexaminations of the fundus, including the macula, prior to treatment initiation with ponesimod andhave follow-up evaluations while receiving therapy.

Respiratory effects

Dose-dependent reductions in forced expiratory volume over 1 second (FEV1) and reductions indiffusion lung capacity for carbon monoxide (DLCO) were observed in ponesimod-treated patientsmostly occurring in the first month after treatment initiation (see section 4.8). Respiratory symptomsassociated with ponesimod treatment can be reversed with administration of a short-acting beta2agonist.

Ponesimod should be used with caution in patients with severe respiratory disease, pulmonary fibrosisand chronic obstructive pulmonary disease. Spirometry evaluation of respiratory function should beperformed during therapy with ponesimod if clinically indicated.

Liver injury

Elevations of transaminases may occur in ponesimod-treated patients (see section 4.8). Recent (i.e.,within last 6 months) transaminase and bilirubin levels should be reviewed before initiation ofponesimod therapy.

Patients who develop symptoms suggestive of hepatic dysfunction, such as unexplained nausea,vomiting, abdominal pain, fatigue, anorexia, rash with eosinophilia, or jaundice and/or dark urineduring treatment, should be monitored for hepatotoxicity. Ponesimod should be discontinued ifsignificant liver injury is confirmed (for example, ALT exceeds 3 -fold ULN and total bilirubinexceeds 2 -fold ULN).

Although there are no data to establish that patients with pre-existing liver disease are at increased riskto develop elevated liver function test values when taking ponesimod, caution should be exercisedwhen using ponesimod in patients with a history of significant liver disease (see section 4.2).

A mild reversible increase in blood pressure (mean change less than 3 mmHg) was observed inpatients treated with ponesimod (see section 4.8). Blood pressure should be regularly monitoredduring treatment with ponesimod and managed appropriately.

Cutaneous neoplasm

As there is a potential risk of skin malignancies (see section 4.8), patients treated with ponesimodshould be cautioned against exposure to sunlight without protection. These patients should not receiveconcomitant phototherapy with UV-B-radiation or PUVA-photochemotherapy.

Based on animal studies, ponesimod may cause foetal harm. Due to the risk to the foetus, ponesimodis contraindicated during pregnancy and in women of childbearing potential not using effectivecontraception (see sections 4.3 and 4.6). Before initiation of treatment in women of childbearingpotential, a negative pregnancy test result must be available (see section 4.6). Because it takesapproximately 1 week to eliminate ponesimod from the body, women of childbearing potential shoulduse effective contraception to avoid pregnancy during and for 1 week after stopping ponesimodtreatment.

Rare cases of posterior reversible encephalopathy syndrome (PRES) have been reported in patientsreceiving a S1P receptor modulator. Such events have not been reported for ponesimod-treatedpatients in the development program. However, should a ponesimod-treated patient develop anyunexpected neurological or psychiatric symptoms/signs (e.g., cognitive deficits, behavioural changes,cortical visual disturbances, or any other neurological cortical symptoms/signs), any symptom/signsuggestive of an increase of intracranial pressure, or accelerated neurological deterioration, thephysician should promptly schedule a complete physical and neurological examination and shouldconsider a MRI. Symptoms of PRES are usually reversible but may evolve into ischaemic stroke orcerebral haemorrhage. Delay in diagnosis and treatment may lead to permanent neurological sequelae.

If PRES is suspected, ponesimod should be discontinued.

Return of disease activity after ponesimod discontinuation

Severe exacerbation of disease, including disease rebound, has been rarely reported afterdiscontinuation of a S1P receptor modulator. The possibility of severe exacerbation of disease shouldbe considered after stopping ponesimod treatment. Patients should be observed for a severeexacerbation or return of high disease activity upon ponesimod discontinuation and appropriatetreatment should be instituted, as required (see above).

After stopping Ponvory in the setting of PML, monitor for development of immune reconstitutioninflammatory syndrome (PML-IRIS) (see above).

Ponvory contains lactose (see section 2). Patients with rare hereditary problems of galactoseintolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinalproduct.

This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially‘sodium-free’.

Anti-neoplastic, immune-modulating, or immunosuppressive therapies

Ponesimod has not been studied in combination with anti-neoplastic, immune-modulating, orimmunosuppressive therapies. Caution should be used during concomitant administration because ofthe risk of additive immune effects during such therapy and in the weeks following administration (seesection 4.4).

Anti-arrhythmic medicinal products, QT prolonging medicinal products, medicinal products that maydecrease heart rate

Ponesimod has not been studied in patients taking QT prolonging medicinal products (see section 4.4).

Beta-blockers

The negative chronotropic effect of co-administration of ponesimod and propranolol was evaluated ina dedicated pharmacodynamics safety study. The addition of ponesimod to propranolol at steady-statehas an additive effect on HR effect.

In a drug-drug interaction study, the up-titration regimen of ponesimod (see section 4.2) wasadministered to subjects receiving propranolol (80 mg) once daily at steady-state. Compared toponesimod alone, the combination with propranolol after the first dose of ponesimod (2 mg) had a12.4 bpm (90% CI: -15.6 to -9.1) decrease in mean hourly heart rate and at the first dose of ponesimod(20 mg) after up-titration a 7.4 bpm (90% CI: -10.9 to -3.9) decrease in mean hourly heart rate. Nosignificant changes in pharmacokinetics of ponesimod or propranolol were observed.

Vaccines

Vaccinations may be less effective if administered while being treated with ponesimod and up to1 week after its discontinuation (see section 4.4).

The use of live attenuated vaccines may carry the risk of infection and should therefore be avoidedduring ponesimod treatment and up to 1 week after its discontinuation of treatment with ponesimod(see section 4.4).

Effect of other medicinal products on ponesimod

Medicinal products that are inhibitors of major CYP or UGT enzymes are unlikely to impact thepharmacokinetics of ponesimod (see section 5.2).

No dose adjustment is needed when ponesimod is co-administered with strong CYP3A4 and UGT1A1inducers. Co-administration of carbamazepine 300 mg twice daily (a strong CYP3A4 and UGT1A1inducer) at steady-state decreased ponesimod Cmax by 19.6% and AUC by 25.7%. This decrease is notclinically relevant.

Ponesimod is not a substrate of P-gp, BCRP, OATP1B1 or OATP1B3 transporters. Medicinalproducts that are inhibitors of these transporters are unlikely to impact the pharmacokinetics ofponesimod.

Effect of ponesimod on other medicinal products

Ponesimod and its metabolites are unlikely to show any clinically relevant drug-drug interactionpotential for CYP or UGT enzymes, or transporters (see section 5.2).

Co-administration of ponesimod, with an oral hormonal contraceptive (containing 1 mgnorethisterone/norethindrone and 35 mcg ethinyl estradiol) showed no clinically relevantpharmacokinetic interaction with ponesimod. Therefore, concomitant use of ponesimod is notexpected to decrease the efficacy of hormonal contraceptives. No interaction studies have beenperformed with oral contraceptives containing other progestogens; however, an effect of ponesimodon their exposure is not expected.

Interaction studies have only been performed in adults.

Ponvory is contraindicated in women of childbearing potential not using effective contraception (seesection 4.3). Before initiation of Ponvory treatment in women of childbearing potential a negativepregnancy test result must be available, and women should be counselled on the potential for a seriousrisk to the foetus and the need for effective contraception during treatment with ponesimod. Since ittakes approximately 1 week to eliminate ponesimod from the body after stopping treatment, thepotential risk to the foetus may persist and women must use effective contraception during this period(see section 4.4).

Specific measures are also included in the Healthcare Professional checklist. These measures must beimplemented before ponesimod is prescribed to female patients and during treatment.

When stopping ponesimod therapy for planning a pregnancy the possible return of disease activityshould be considered (see section 4.4).

Ponvory is contraindicated during pregnancy (see section 4.3). Although there are no data from the useof ponesimod in pregnant women, studies in animals have shown reproductive toxicity (seesection 5.3). If a woman becomes pregnant during treatment, ponesimod must be immediatelydiscontinued. Medical advice should be given regarding the risk of harmful effects to the foetusassociated with treatment (see section 5.3) and follow-up examinations should be performed.

Based on clinical experience in patients receiving another S1P receptor modulator, the use isassociated with an increased risk of major congenital malformations.

It is unknown whether ponesimod or its metabolites are excreted in human milk. A study in lactatingrats has indicated excretion of ponesimod in milk (see section 5.3). A risk to newborns/infants cannotbe excluded. Ponvory should not be used during breast-feeding.

The effect of ponesimod on human fertility has not been evaluated. Data from preclinical studies donot suggest that ponesimod would be associated with an increased risk of reduced fertility (seesection 5.3).

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

The most commonly reported adverse drug reactions are nasopharyngitis (19.7%), alanineaminotransferase increased (17.9%) and upper respiratory tract infection (11%).

Adverse reactions reported with ponesimod in controlled clinical trials and uncontrolled extensiontrials are ranked by frequency, with the most frequent reactions first. Frequencies were defined usingthe following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to<1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from theavailable data).

Table 2: Tabulated list of adverse reactions

System Organ

Class (SOC) Very common Common Uncommonurinary tract infection,bronchitis, influenza,nasopharyngitis, upper rhinitis, respiratory tract

Infections and respiratory tract infection, respiratory tractinfestations infection infection viral,pharyngitis, sinusitis, viralinfection, herpes zoster,laryngitis, pneumonia

Blood andlymphatic system lymphopenia, lymphocytedisorders count decreased

Psychiatric depression, insomnia,disorders anxiety

Nervous system dizziness, hypoaesthesia,disorders somnolence, migraine,seizure

Eye disorders macular oedema

Ear and labyrinthdisorders vertigo

Cardiac disorders bradycardia

Vascular disorders hypertension

Respiratory,thoracic andmediastinal dyspnoea, coughdisorders

Gastrointestinaldisorders dyspepsia dry mouth

Musculoskeletal back pain, arthralgia, painand connective in extremity, ligament joint swellingtissue disorders sprain

General disordersand fatigue, pyrexia, oedemaadministration site peripheral, chestconditions discomfortaspartate aminotransferaseincreased,alanine hypercholesterolaemia,

Investigations aminotransferase hepatic enzyme increased,increased C-reactive protein hyperkalaemiaincreased, transaminasesincreased, bloodcholesterol increased

Bradyarrhythmia

In the Phase 3 OPTIMUM study (see section 5.1), bradycardia at treatment initiation (sinusbradycardia/HR less than 50 bpm on ECG on day 1) occurred in 5.8% of ponesimod-treated patientscompared to 1.6% of patients receiving teriflunomide 14 mg. Patients who experienced bradycardiawere generally asymptomatic. Bradycardia resolved in all patients without intervention and did notrequire discontinuation of ponesimod treatment. On day 1, 3 patients treated with ponesimod hadasymptomatic post-dose HR below or equal to 40 bpm; all 3 patients had baseline HRs below 55 bpm.

Initiation of ponesimod treatment has been associated with transient AV conduction delays that followa similar temporal pattern as the observed decrease in HR during dose titration. The AV conductiondelays manifested as first-degree AV block (prolonged PR interval on ECG), which occurred in 3.4%of ponesimod -treated patients and in 1.2% of patients receiving teriflunomide 14 mg in the

OPTIMUM study. No second-degree AV blocks, Mobitz type I (Wenckebach), were observed in

OPTIMUM. The conduction abnormalities typically were transient, asymptomatic, resolved within24 hours, resolved without intervention, and did not require discontinuation of ponesimod treatment.

In the Phase 3 OPTIMUM study (see section 5.1), the overall rate of infections was comparablebetween the ponesimod-treated patients and those receiving teriflunomide 14 mg (54.2% vs 52.1%respectively). Nasopharyngitis and viral infections were more common in ponesimod-treated patients.

Serious or severe infections occurred at a rate of 1.6% in ponesimod-treated patients compared to0.9% of patients receiving teriflunomide 14 mg.

In OPTIMUM, the rate of herpetic infections was not different between the ponesimod-treated patientsand those receiving teriflunomide 14 mg (4.8%).

Blood lymphocyte count reduction

In OPTIMUM, 3.2% of ponesimod-treated patients compared to none of the patients receivingteriflunomide 14 mg, experienced lymphocyte counts less than 0.2 × 109/L with values generallyresolving to greater than 0.2 × 109/L while remaining on treatment with ponesimod.

Macular oedema

In OPTIMUM, macular oedema was reported in 1.1% of ponesimod-treated patients compared to noneof the patients receiving teriflunomide 14 mg.

Liver enzymes elevation

In the OPTIMUM study, ALT increased to three and five times the upper limit of normal (ULN) in17.3% and 4.6% of ponesimod-treated patients, respectively, compared to 8.3% and 2.5% of patientsreceiving, teriflunomide 14 mg, respectively. ALT increased eight times ULN in 0.7%ponesimod-treated patients compared to 2.1% in patients receiving teriflunomide 14 mg. The majorityof elevations occurred within 6 or 12 months of starting treatment. ALT levels returned to normal afterdiscontinuation of ponesimod. Most cases of ALT increases ≥3×ULN resolved on continuedponesimod treatment, and the remaining cases resolved upon treatment discontinuation. In clinicaltrials, ponesimod was discontinued if the elevation exceeded a 3 -fold increase and the patient showedsymptoms related to hepatic dysfunction.

Respiratory effects

Dose-dependent reductions in forced expiratory volume over 1 second (FEV1) were observed inpatients treated with ponesimod (see section 4.4). In OPTIMUM, a higher proportion ofponesimod-treated patients (19.4%) had a reduction of more than 20% from baseline in percentpredicted FEV1 compared to 10.6% of patients receiving teriflunomide 14 mg. The reduction frombaseline in percent predicted FEV1 at 2 years was 8.3% in ponesimod-treated patients compared to4.4% in patients receiving teriflunomide 14 mg. The changes in FEV1 and DLCO appear to be partiallyreversible after treatment discontinuation. In the OPTIMUM study, 7 patients discontinued ponesimodbecause of pulmonary adverse events (dyspnoea). Ponesimod has been tested in MS patients with mildto moderate asthma or chronic obstructive pulmonary disease. The changes in FEV1 were similar inthis subgroup compared with the subgroup of patients without baseline lung disorders.

In OPTIMUM, ponesimod-treated patients had an average increase of 2.9 mmHg in systolic bloodpressure and 2.8 mmHg in diastolic blood pressure compared to 2.8 mmHg and 3.1 mmHg in patientsreceiving teriflunomide 14 mg, respectively. An increase in blood pressure with ponesimod was firstdetected after approximately 1 month of treatment initiation and persisted with continued treatment.

The blood pressure values after ponesimod treatment discontinuation indicate reversibility.

Hypertension was reported as an adverse reaction in 10.1% of ponesimod-treated patients and in 9.0%of patients receiving teriflunomide 14 mg.

Cutaneous neoplasm

In OPTIMUM, a case of malignant melanoma and two cases of basal cell carcinoma (0.4%) werereported in ponesimod-treated patients compared to one case of basal cell carcinoma (0.2%) in patientsreceiving teriflunomide 14 mg. An increased risk of cutaneous malignancies has been reported inassociation with another S1P receptor modulator.

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.

Symptoms and signs

In patients with overdose of ponesimod, especially upon initiation/re-initiation of treatment, it isimportant to observe for signs and symptoms of bradycardia as well as AV conduction blocks, whichmay include overnight monitoring. Regular measurements of pulse rate and blood pressure arerequired, and ECGs should be performed (see sections 4.4, pct. 4.8 and 5.1).

There is no specific antidote to ponesimod. Neither dialysis nor plasma exchange would result inmeaningful removal of ponesimod from the body. The decrease in heart rate induced by ponesimodcan be reversed by atropine.

In the event of overdose, ponesimod should be discontinued, and general supportive treatment givenuntil clinical toxicity has been diminished or resolved. It is advisable to contact a poison control centreto obtain the latest recommendations for the management of an overdose.

Pharmacotherapeutic group: Immunosuppressants, selective immunosuppressants, ATC code:

L04AE04

Ponesimod is a sphingosine 1-phosphate (S1P) receptor 1 modulator. Ponesimod binds with highaffinity to S1P receptor 1 located on lymphocytes.

Ponesimod blocks the capacity of lymphocytes to egress from lymph nodes reducing the number oflymphocytes in peripheral blood. The mechanism by which ponesimod exerts therapeutic effects inmultiple sclerosis may involve reduction of lymphocyte migration into the central nervous system.

Immune system

In healthy volunteers, ponesimod induces a dose-dependent reduction of the peripheral bloodlymphocyte count from a single dose of 5 mg onwards, with the greatest reduction observed 6 hourspost-dose, caused by reversible sequestration of lymphocytes in lymphoid tissues. After 7 daily dosesof 20 mg, the greatest decrease in absolute mean lymphocyte count was to 26% of baseline(650 cells/µL), observed 6 hours after administration. Peripheral blood B cells [CD19+] and T cells[CD3+], T-helper [CD3+CD4+], and T-cytotoxic [CD3+CD8+] cell subsets are all affected, while NKcells are not. T-helper cells were more sensitive to the effects of ponesimod than T-cytotoxic cells.

Pharmacokinetic/Pharmacodynamic modelling indicates lymphocyte counts returned to the normalrange in >90% of healthy subjects within 1 week of stopping therapy. In the development program,peripheral lymphocyte counts returned to the normal range within 1 week after discontinuation ofponesimod.

In the OPTIMUM study, lymphocyte counts returned to the normal range in 94% of patients and toabove 0.8 × 109 cells/L in 99% of patients at the first scheduled follow-up visit (day 15) upondiscontinuation of ponesimod treatment.

Heart rate and rhythm

Ponesimod causes a transient dose dependent reduction in HR and AV conduction delays upontreatment initiation (see section 4.4). The HR decreases plateaued at doses greater than or equal to40 mg, and bradyarrhythmic events (AV blocks) were detected at a higher incidence under ponesimodtreatment, compared to placebo. This effect starts within the first hour of dosing and is maximal at2-4 hours post-dose and HR generally returns to pre-dose values by 4-5 hours post-dose on day 1 andthe effect diminishes with repeated administration, indicating tolerance.

With the gradual up-titration of ponesimod, the HR reduction is less pronounced and no second-degree

AV blocks of Mobitz type II or higher degree were observed.

The decrease in HR induced by ponesimod can be reversed by atropine.

Effect on QT/QTc interval and cardiac electrophysiology

In a thorough QT study of supra-therapeutic doses of 40 mg and 100 mg (2 - and 5 -fold respectively,the recommended maintenance dose) ponesimod at steady-state, ponesimod treatment resulted in mildprolongation of individually corrected QT (QTcI) interval, with the upper bound of 90% two-sidedconfidence interval (CI) at 11.3 ms (40 mg) and 14.0 ms (100 mg). There was no consistent signal ofincreased incidence of QTcI outliers associated with ponesimod treatment, either as absolute values orchange from baseline. Based on the concentration-effect relationship, no clinically relevant effect on

QTc interval is expected for the therapeutic dose of 20 mg (see section 4.4).

Pulmonary function

Dose-dependent reductions in absolute forced expiratory volume over 1 second were observed inponesimod-treated subjects and were greater than in subjects taking placebo (see section 4.8).

The efficacy of ponesimod was evaluated in the Phase 3 study, OPTIMUM, a multicentre,randomised, double blind, parallel group active-controlled superiority study in patients with relapsing

MS (RMS) treated for 108 weeks. The study included patients with relapsing course of MS from onset(RRMS or SPMS with superimposed relapses) and an Expanded Disability Status Scale (EDSS) scoreof 0 to 5.5, having experienced at least one relapse within the prior year, or two relapses within theprior two years, or having at least one gadolinium-enhancing (Gd+) lesion on a brain MRI within theprior 6 months or at baseline.

Patients were randomised to receive either once daily ponesimod or teriflunomide 14 mg, beginningwith a 14-day dose titration (see section 4.2). Neurological evaluations were performed every12 weeks as well as at the time of a suspected relapse. Brain MRIs were performed at baseline and at

Weeks 60 and 108.

The primary endpoint of the study was the annualised relapse rate (ARR) from baseline up to end ofstudy (EOS). The prespecified hierarchical fallback testing sequence included the primary endpointand the secondary endpoints: cumulative number of combined unique active lesions (CUAL, definedas new Gd+ T1 lesions plus new or enlarging T2 lesions [without double-counting of lesions]) frombaseline to Week 108; time to 12-week confirmed disability accumulation (CDA) from baseline to

EOS; and time to 24-week CDA from baseline to EOS. A 12-week CDA was defined as an increase ofat least 1.5 in EDSS for subjects with a baseline EDSS score of 0 or an increase of at least 1.0 in EDSSfor subjects with a baseline EDSS score of 1.0 to 5.0, or an increase of at least 0.5 in EDSS forsubjects with a baseline EDSS score ≥5.5 which was confirmed after 12 weeks.

In OPTIMUM, 1133 patients were randomised to either ponesimod (N=567) or teriflunomide 14 mg(N=566); 86.4% of ponesimod-treated patients and 87.5% of teriflunomide 14 mg-treated patientscompleted the study as per protocol. The baseline demographic and disease characteristics werebalanced between the treatment groups. At baseline, the mean age of patients was 37 years (standarddeviation 8.74), 97% were white and 65% were female. The mean disease duration was 7.6 years, themean number of relapses in the previous year was 1.3, and the mean EDSS score was 2.6; 57% ofpatients had not received any prior disease-modifying treatments (DMT) for MS. At baseline, 40% ofponesimod-treated patients had one or more Gd+ T1 lesions on brain MRI (mean 1.9).

Results are presented in Table 3. Analysis of patient populations with differing baseline levels ofdisease activity, including active and highly active disease, showed that the efficacy of ponesimod onthe primary and secondary endpoints was consistent with the overall population.

Table 3: OPTIMUM study efficacy results

Ponesimod 20 mg Teriflunomide 14 mg

Clinical endpoint N=567 N=566

Primary endpoint

Mean Annualised Relapse Ratea 0.202 0.290

*

Relative rate reduction 30.5% (p=0.0003)(95% CLs: 15.2%, 43.0%)

Patients with at least one confirmedrelapse 29.3% 39.4%

Secondary endpoints

Confirmed Disability Accumulation(CDA) b N=567 N=566

Patientsb with 12-week CDA 10.8% 13.2%

Relative risk reductionc 17% (p=0.2939)(95% CLs: -18%, 42%)

Patientsb with 24-week CDA 8.7% 10.5%

Relative risk reductionc 16% (p=0.3720)(95% CLs: -24%, 43%)

MRI Endpoints

Cumulative number of Combined

Unique Active Lesions (CUALs) N=539 N=536

Mean number of CUALs per yeard 1.41 3.16

*

Relative reduction 56% (p<0.0001)(95% CLs: 45.8%, 63.6%)

All analyses are based on the full analysis set (FAS), which includes all randomised patients.“N” refers to the number ofpatients included in each of the endpoint analysis, per treatment group.a Defined as confirmed relapses per year up to end of study (negative binomial regression model with stratificationvariables (EDSS ≤ 3.5 versus EDSS > 3.5; DMT within last 2 years prior to randomisation [Yes/No]) and the numberof relapses in the year prior to study entry(<=1, >=2) as covariates)b Based on time to first 12-Week/24-Week CDA event up to end of study (Kaplan-Meier estimates at Week 108)c Defined as time to 12-Week/24-Week CDA from baseline to end of study (Stratified Cox proportional hazard model, pvalue based on the stratified log rank test). Two pre-planned indirect comparison methods both showed a consistentclinically meaningful effect of ponesimod compared to placebo on time to first 12-week CDA, the Matching-Adjusted

Indirect Comparison (MAIC) approach showed that ponesimod reduced 12-week CDA by 40% compared to placebo(hazard ratio: 0.60 [95% CI: 0.34, 1.05]) and the Model-Based Meta-Analysis (MBMA) showed that ponesimodreduced the risk of 12-week CDA by 39% compared to placebo (hazard ratio: 0.61 [95% CLs: 0.47, 0.80]).

d Defined as new Gd+ T1 lesions plus new or enlarging T2 lesions [without double-counting of lesions] per year frombaseline to Week 108 (Negative binomial regression model with stratification factors and Gd+ T1 lesions(present/absent) at baseline as covariates)

* Statistically significant according to the predefined multiplicity testing strategy, CLs: Confidence Limits

The European Medicines Agency has deferred the obligation to submit the results of studies with

Ponvory in one or more subsets of the paediatric population in the treatment of multiple sclerosis(see 4.2 for information on paediatric use).

The pharmacokinetics of ponesimod is similar in healthy subjects and subjects with multiple sclerosis.

The pharmacokinetic profile of ponesimod showed “low to moderate” inter-subject variability,approximately 6% - 33%, and “low” intra-subject variability, approximately 12% - 20%.

The time to reach maximum plasma concentration of ponesimod is 2-4 hours post-dose. The absoluteoral bioavailability of a 10 mg dose is 83.8%.

Food does not have a clinically relevant effect on ponesimod pharmacokinetics, therefore ponesimodmay be taken with or without food.

Following intravenous administration in healthy subjects, the steady-state volume of distribution ofponesimod is 160 L.

Ponesimod is highly bound to plasma proteins, (> 99%) and is mainly (78.5%) distributed in theplasma fraction of whole blood. Animal studies show that ponesimod readily crosses theblood-brain-barrier.

Ponesimod is extensively metabolised prior to excretion in humans, though unchanged ponesimod wasthe main circulating component in plasma. Two inactive circulating metabolites, M12 and M13, havealso been identified in human plasma. M13 is approximately 20% and M12 is 6% of total drug-relatedexposure. Both metabolites are inactive at S1P receptors at concentrations achieved with therapeuticdoses of ponesimod.

In vitro studies with human liver preparations indicate that metabolism of ponesimod occurs throughmultiple, distinct enzyme systems, including multiple CYP450 (CYP2J2, CYP3A4, CYP3A5,

CYP4F3A, and CYP4F12), UGT (mainly UGT1A1 and UGT2B7) and non CYP450 oxidativeenzymes, without major contribution by any single enzyme.

In vitro investigations indicate that at the therapeutic dose of 20 mg once-daily, ponesimod and itsmetabolite M13 do not show any clinically relevant drug-drug interaction potential for CYP or UGTenzymes, or transporters.

After a single intravenous administration, the total clearance of ponesimod is 3.8 L/hour. Theelimination half-life after oral administration is approximately 33 hours.

Following a single oral administration of 14C-ponesimod, 57% to 80% of the dose was recovered infaeces (16% as unchanged ponesimod), and 10% to18% in urine (no unchanged ponesimod).

Following ponesimod oral dosing, Cmax and AUC increased approximately dose proportionally in thedose range studied (1-75 mg). Steady-state levels are approximately 2.0 to 2.6 -fold greater than with asingle dose and are achieved following 4 days of administration of the maintenance dose ofponesimod.

No dose adjustment is necessary in patients with renal impairment. In adult subjects with moderate orsevere renal impairment (estimated creatinine clearance (CrCl) as determined by the Cockroft-Gaultbetween 30-59 mL/min for moderate and <30 mL/min for severe), there were no significant changes inponesimod Cmax and AUC compared to subjects with normal renal function (CrCl>90 mL/min). Theeffect of dialysis on the pharmacokinetics of ponesimod has not been studied. Due to the high plasmaprotein binding (greater than 99%) of ponesimod, dialysis is not expected to alter the total andunbound ponesimod concentration and no dose adjustments are anticipated based on theseconsiderations.

In adult subjects without MS with mild, moderate or severe hepatic impairment (Child-Pugh class A,

B and C, respectively, N=8 for each category), ponesimod AUC0-∞ was increased by 1.3-, 2.0- and3.1 -fold respectively compared to healthy subjects. Based on the population pharmacokineticassessment in a larger group of subjects (N=1245), including 55 subjects with MS with mild hepaticimpairment (classified based on the National Cancer Institute - Organ Dysfunction Working Groupcriteria), a 1.1-fold increase of ponesimod AUC0-∞ was estimated, compared to subjects with normalhepatic function.

Ponesimod is contraindicated in patients with moderate and severe hepatic impairment, as the risk ofadverse reactions may be greater.

No dose adjustment is needed in patients with mild hepatic impairment (Child-Pugh class A).

The results from a population pharmacokinetics analysis indicated that age (range: 17 to 65 years)does not significantly influence the pharmacokinetics of ponesimod. Ponesimod has not beeninvestigated in the elderly population (>65 years).

Gender has no clinically significant influence on ponesimod pharmacokinetics.

No clinically relevant pharmacokinetic differences were observed between Japanese and Caucasian or

Black and White subjects.

In the lung, transient adaptive pulmonary histiocytosis and lung weight increase were observed inmice, rats, and dogs after 4 weeks of administration of ponesimod but were no longer present or wereless pronounced after 13 to 52 weeks of administration. The no-observed-adverse-effect levels(NOAELs) for lung findings were identified in rat and dog 4-week toxicity studies and wereassociated with Cmax and AUC0-24 values similar or inferior to human systemic exposures followingrecommended human dose (RHD) of 20 mg/day.

In the dog, arterial lesions observed in the heart were secondary to haemodynamic changes. The dog isknown to be particularly sensitive to haemodynamic changes in the heart and the associated toxicitymay be species specific and not predictive of a risk in humans. When compared with human systemicexposures at RHD of 20 mg/day the NOAEL in the dog was 4.3 and 6.2 times the human systemicexposures based on AUC0-24 and Cmax, respectively.

Ponesimod did not reveal a genotoxic potential in vitro and in vivo.

Oral carcinogenicity studies of ponesimod were conducted in mice and rats for up to 2 years. In rats,no neoplastic lesions were observed up to the highest dose tested, corresponding with a plasmaponesimod exposure (AUC) which is 18.7 times that in humans at the RHD of 20 mg. In mice,ponesimod increased the combined total incidence of hemangiosarcoma and hemangioma in all treatedmales and high dose females. The lowest dose tested in females is the no-observed-effect-level(NOEL) for carcinogenesis, and the AUC0-24 is 2.4 times the human systemic exposures at RHD of20 mg.

Fertility and reproductive toxicity

Ponesimod had no effect on male and female fertility in rats at plasma exposures (AUC) up toapproximately 18 and 31 times (for males and females, respectively) that in humans at the RHD of20 mg/day.

When ponesimod was orally administered to pregnant rats during the period of organogenesis,embryo-foetal survival, growth, and morphological development were severely compromised.

Teratogenic effects with major skeletal and visceral abnormalities were also observed. Whenponesimod was orally administered to pregnant rabbits during the period of organogenesis, a slightincrease in post-implantation losses and foetal findings (visceral and skeletal) were noted. Plasmaexposure (AUC) in rats and rabbits at the NOAEL (1 mg/kg/day in both species) is less than that inhumans at the RHD of 20 mg/day.

When ponesimod was orally administered to female rats throughout pregnancy and lactation,decreased pup survival and body weight gain, and delayed sexual maturation were observed in theoffspring at the highest dose tested. Fertility of the F1 females was reduced. The AUC0-24 at the

NOAEL of 10 mg/kg/day is 1.2 to 1.5 times that in humans at the RHD of 20 mg/day. Ponesimod waspresent in the plasma of F1 pups, indicating exposure from the milk of the lactating dam.

Croscarmellose sodium

Lactose monohydrate

Magnesium stearate

Microcrystalline cellulose

Povidone K30

Silica colloidal anhydrous

Sodium laurilsulfate

Hypromellose 2910

Lactose monohydrate

Macrogol 3350

Titanium dioxide

Triacetin

Ponvory 3 mg film-coated tablets

Iron oxide red (E172)

Iron oxide yellow (E172)

Ponvory 4 mg film-coated tablets

Iron oxide red (E172)

Black iron oxide (E172)

Ponvory 5 mg film-coated tablets

Black iron oxide (E172)

Iron oxide yellow (E172)

Ponvory 7 mg film-coated tablets

Iron oxide red (E172)

Iron oxide yellow (E172)

Ponvory 8 mg film-coated tablets

Iron oxide red (E172)

Black iron oxide (E172)

Ponvory 9 mg film-coated tablets

Iron oxide red (E172)

Black iron oxide (E172)

Iron oxide yellow (E172)

Ponvory 10 mg film-coated tablets

Iron oxide red (E172)

Iron oxide yellow (E172)

Ponvory 20 mg film-coated tablets

Iron oxide yellow (E172)

Not applicable.

4 years

This medicinal product does not require any special storage conditions.

The Alu/alu blister with desiccant consists of a laminated Alu cold form film with integrated desiccantand a laminated Alu push-through lidding film.

Treatment initiation pack

Each blister pack of 14 film-coated tablets for a 2-week treatment schedule contains:2 film-coated tablets of 2 mg2 film-coated tablets of 3 mg2 film-coated tablets of 4 mg1 film-coated tablet of 5 mg1 film-coated tablet of 6 mg1 film-coated tablet of 7 mg1 film-coated tablet of 8 mg1 film-coated tablet of 9 mg3 film-coated tablets of 10 mg

Ponvory 20 mg film-coated tablets (maintenance pack)

Pack of 28 film-coated tablets or multipack containing 84 (3 packs of 28) film-coated tablets.

Not all pack sizes may be marketed.

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

LABORATOIRES JUVISE PHARMACEUTICALS149 Boulevard Bataille de Stalingrad69100 Villeurbanne

France

EU/1/21/1550/001

EU/1/21/1550/002

EU/1/21/1550/003

Date of first authorisation: 19 May 2021