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Adverse events reporting | Prescribing informationPONVORY® (ponesimod) ( This product is under additional monitoring)

The safety results for PONVORY® from the large Phase III OPTIMUM study were in line with previous observations in its Phase II dose-finding study and the known profile of other S1PR modulators2

Similar rates of overall TEAEs vs teriflunomide2

• Overall, the proportion of patients experiencing at least 1 TEAE or SAE was similar between the 2 treatment groups2
• The majority of TEAEs were mild to moderate and did not result in treatment discontinuation2

Safety set
PONVORY® 20mg

n = 565
Teriflunomide 14mg

n = 566
Safety set
PONVORY® 20mg

n = 565

n (%)

Teriflunomide 14mg

n = 566

n (%)

Safety set
TEAEs
PONVORY® 20mg

n = 565

502 (88.8%)

Teriflunomide 14mg

n = 566

499 (88.2%)

Safety set

SAEs

PONVORY® 20mg

n = 565

49 (8.7%)

Teriflunomide 14mg

n = 566

46 (8.1%)

Safety set
TEAEs leading to treatment discontinuation
PONVORY® 20mg

n = 565

49 (8.7%)

Teriflunomide 14mg

n = 566

34 (6.0%)

Safety set
Fatal TEAEs
PONVORY® 20mg

n = 565

0 (0%)

Teriflunomide 14mg

n = 566

2 (0.4%)

TEAE=treatment-emergent adverse event; SAE=serious adverse event

Most frequent TEAEs2

• The most frequent TEAEs were an increased ALT level, nasopharyngitis, headache, upper respiratory tract infection, and alopecia in the 2 treatment groups2

Safety set
PONVORY® 20mg

n = 565
Teriflunomide 14mg

n = 566
Safety set
Most frequent TEAEs (> 10% in either group)
PONVORY® 20mg

n = 565
Teriflunomide 14mg

n = 566
Safety set
PONVORY® 20mg

n = 565

n (%)

Teriflunomide 14mg

n = 566

n (%)

Safety set

ALT increase

PONVORY® 20mg

n = 565

110 (19.5%)

Teriflunomide 14mg

n = 566

53 (9.4%)

Safety set

Nasopharyngitis

PONVORY® 20mg

n = 565

109 (19.3%)

Teriflunomide 14mg

n = 566

95 (16.8%)

Safety set

Headache

PONVORY® 20mg

n = 565

65 (11.5%)

Teriflunomide 14mg

n = 566

72 (12.7%)

Safety set

Upper respiratory tract infection

PONVORY® 20mg

n = 565

60 (10.6%)

Teriflunomide 14mg

n = 566

59 (10.4%)

Safety set
Alopecia
PONVORY® 20mg

n = 565

18 (3.2%)

Teriflunomide 14mg

n = 566

72 (12.7%)

View TE-AESI: Liver

• All alanine transaminase (ALT) level increases ≥3x upper limit of normal (ULN) resolved despite continued PONVORY® treatment or after treatment discontinuation2
• Rate of ALT level increase ≥8x ULN was lower in the PONVORY® group compared to teriflunomide2

Elevation of transaminases and bilirubin may occur in patients taking PONVORY®. Before treatment initiation, results of a liver function test obtained within the last 6 months should be reviewed. Patients who develop symptoms suggestive of hepatic dysfunction during treatment with PONVORY® should be monitored for hepatotoxicity, and treatment should be discontinued if significant liver injury is confirmed (e.g., alanine aminotransferase [ALT] exceeds 3x upper limit of normal [ULN] and total bilirubin exceeds 2x ULN).1

TE-AESI: SUMMARY OF LIVER TEST ABNORMALITIES UP TO END OF TREATMENT+ 1 DAY, SAFETY SET1-3

Elevation
PONVORY® 20mg

n = 560
Teriflunomide 14mg

n = 566
Elevation
PONVORY® 20mg

n = 560

n (%)

Teriflunomide 14mg

n = 566

n (%)

Elevation

ALT ≥ 3 x ULN

PONVORY® 20mg

n = 560

97 (17.3 %)

Teriflunomide 14mg

n = 566

47 (8.3%)

Elevation

ALT ≥ 5 x ULN

PONVORY® 20mg

n = 560

26 (4.6%)

Teriflunomide 14mg

n = 566

14 (2.5%)

Elevation

ALT ≥ 8 x ULN

PONVORY® 20mg

n = 560

4 (0.7%)

Teriflunomide 14mg

n = 566


12 (2.1%)


Elevation

ALT ≥ 10 x ULN

PONVORY® 20mg

n = 560

3 (0.5%)

Teriflunomide 14mg

n = 566

10 (1.8%)

Elevation

ALT ≥ 20 x ULN

PONVORY® 20mg

n = 560

0 (-%)

Teriflunomide 14mg

n = 566

2 (0.4%)

Elevation

TBIL ≥ 2 x ULN

PONVORY® 20mg

n = 560

8 (1.4%)

Teriflunomide 14mg

n = 566

2 (0.4%)

Elevation

ALT or AST ≥ 3 x ULN + TBIL ≥ 2 x ULN

PONVORY® 20mg

n = 560

1* (0.2%)

Teriflunomide 14mg

n = 566

0 (-)

ALT=alanine transaminase; AST=aspartate aminotransferase; TBIL=total bilirubin; TE-AESI=treatment-emergent adverse events of special interest.

*Patient with pre-existing ALT elevation >5x ULN and resolved after discontinuation.3
ALT ULN: 44 U/L (male) and 33 U/L (female). AST ULN: 39 U/L (male) and 34 U/L (female).3

View TE-AESI: Cardiac

• In all patients, a gradual up-titration is required for initiation of PONVORY® treatment to mitigate first-dose effects2
• The cardiac adverse events on Day 1 were neither serious nor led to permanent discontinuation of treatment2

• In the OPTIMUM study, bradycardia at treatment initiation (sinus bradycardia on electrocardiogram [heart rate less than 50 bpm]) occurred in 5.8% of patients treated with PONVORY® compared with 1.6% of patients receiving teriflunomide1
• No second-degree atrioventricular (AV) blocks, Mobitz type I (Wenckebach), were observed in the OPTIMUM study. The conduction abnormalities typically were transient, asymptomatic, resolved within 24 hours, resolved without intervention, and did not require discontinuation of PONVORY® treatment1


Prior to initiation of treatment:
obtain an electrocardiogram (ECG) to determine whether a first-dose observation (FDO) is needed. FDO is required in select patients with pre-existing cardiac conditions. Review results of a recent complete blood count (CBC) with differential white blood cell (WBC) count obtained within 6 months prior to treatment initiation or after discontinuation of prior therapy. Recent (i.e. within 6 months) transaminase and bilirubin levels should be reviewed before initiation. Obtain an evaluation of the fundus, including the macula. Women should obtain a negative pregnancy test prior to initiating treatment.1
Refer to the SmPC for further information on requirements prior to treatment initiation.

SUMMARY OF TE-AESIs ON HEART RATE AND RHYTHM ON DAY 1*,

SAFETY ANALYSIS SET1,2

Safety Set
PONVORY® 20mg

n = 565
Teriflunomide 14mg

n = 566
Safety Set
PONVORY® 20mg

n = 565

n (%)

Teriflunomide 14mg

n = 566

n (%)

Safety Set

Incidence of Treatment-Emergent AESI

PONVORY® 20mg

n = 565
12 (2.1%)
Teriflunomide 14mg

n = 566
2 (0.4%)
Safety Set

Bradycardia

PONVORY® 20mg

n = 565

 4 (0.7%)

Teriflunomide 14mg

n = 566

0 (-)

Safety Set

Atrioventricular block first degree

PONVORY® 20mg

n = 565

3 (0.5%)

Teriflunomide 14mg

n = 566

0 (-)

Safety Set

Intraventricular conduction delay

PONVORY® 20mg

n = 565

2 (0.4%)

Teriflunomide 14mg

n = 566

0 (-)

Safety Set

Bundle branch block left

PONVORY® 20mg

n = 565

1 (0.2%)

Teriflunomide 14mg

n = 566

0 (-)

Safety Set

Bundle branch block right

PONVORY® 20mg

n = 565

1 (0.2%)

Teriflunomide 14mg

n = 566

0 (-)

Safety Set

Sinus arrhythmia

PONVORY® 20mg

n = 565

1 (0.2%)

Teriflunomide 14mg

n = 566

0 (-)

Safety Set

Sinus bradycardia

PONVORY® 20mg

n = 565

1 (0.2%)

Teriflunomide 14mg

n = 566

0 (-)

Safety Set
Electrocardiogram QT prolonged
PONVORY® 20mg

n = 565

0 (-)

Teriflunomide 14mg

n = 566

1 (0.2%)

Safety Set
Presyncope
PONVORY® 20mg

n = 565

0 (-)

Teriflunomide 14mg

n = 566

1 (0.2%)

For further information on the safety of PONVORY®, please refer to the Summary of Product Characteristics

GET MORE INFORMATION

about the PONVORY® titration schedule

ALT=alanine aminotransferase; S1PR=sphinogosine-1-phosphate receptor; SAE=serious adverse event; TEAE=treatment-emergent adverse event;
TE-AESI=treatment-emergent adverse events of special interest; ULN=upper limit of normal

LEARN MORE about PONVORY® and its efficacy versus teriflunomide1,2
LEARN MORE about PONVORY® and its proven superiority versus teriflunomide
FIND OUT more about how PONVORY® works
References
  1. Ponvory Summary of Product Characteristics Available at: www.medicines.ie
  2. Kappos L, et al. Ponesimod Compared With Teriflunomide in Patients With Relapsing Multiple Sclerosis in the Active-Comparator Phase 3 OPTIMUM Study: A Randomized Clinical Trial. JAMA Neurol. 2021;78(5):558-567. doi:10.1001/jamaneurol.2021.0405.
  3. Kappos L, et al. Supplement 1. Ponesimod Compared With Teriflunomide in Patients With Relapsing Multiple Sclerosis in the Active-Comparator Phase 3 OPTIMUM Study: A Randomized Clinical Trial. JAMA Neurol. 2021. doi:10.1001/jamaneurol.2021.0405.
CP-280405 - February 2022