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 | Teriflunomide 14mg |
|---|---|---|
Safety set | PONVORY® 20mgn (%) | Teriflunomide 14mgn (%) |
Safety set | PONVORY® 20mg502 (88.8%) | Teriflunomide 14mg499 (88.2%) |
Safety setSAEs | PONVORY® 20mg49 (8.7%) | Teriflunomide 14mg46 (8.1%) |
Safety set | PONVORY® 20mg49 (8.7%) | Teriflunomide 14mg34 (6.0%) |
Safety set | PONVORY® 20mg0 (0%) | Teriflunomide 14mg2 (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 | Teriflunomide 14mg |
|---|---|---|
Safety set | PONVORY® 20mg | Teriflunomide 14mg |
Safety set | PONVORY® 20mgn (%) | Teriflunomide 14mgn (%) |
Safety setALT increase | PONVORY® 20mg110 (19.5%) | Teriflunomide 14mg53 (9.4%) |
Safety setNasopharyngitis | PONVORY® 20mg109 (19.3%) | Teriflunomide 14mg95 (16.8%) |
Safety setHeadache | PONVORY® 20mg65 (11.5%) | Teriflunomide 14mg72 (12.7%) |
Safety setUpper respiratory tract infection | PONVORY® 20mg60 (10.6%) | Teriflunomide 14mg59 (10.4%) |
Safety set | PONVORY® 20mg18 (3.2%) | Teriflunomide 14mg72 (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 | Teriflunomide 14mg |
|---|---|---|
Elevation | PONVORY® 20mgn (%) | Teriflunomide 14mgn (%) |
ElevationALT ≥ 3 x ULN | PONVORY® 20mg97 (17.3 %) | Teriflunomide 14mg47 (8.3%) |
ElevationALT ≥ 5 x ULN | PONVORY® 20mg26 (4.6%) | Teriflunomide 14mg14 (2.5%) |
ElevationALT ≥ 8 x ULN | PONVORY® 20mg4 (0.7%) | Teriflunomide 14mg12 (2.1%) |
ElevationALT ≥ 10 x ULN | PONVORY® 20mg3 (0.5%) | Teriflunomide 14mg10 (1.8%) |
ElevationALT ≥ 20 x ULN | PONVORY® 20mg0 (-%) | Teriflunomide 14mg2 (0.4%) |
ElevationTBIL ≥ 2 x ULN | PONVORY® 20mg8 (1.4%) | Teriflunomide 14mg2 (0.4%) |
ElevationALT or AST ≥ 3 x ULN + TBIL ≥ 2 x ULN | PONVORY® 20mg1* (0.2%) | Teriflunomide 14mg0 (-) |
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 | Teriflunomide 14mg |
|---|---|---|
Safety Set | PONVORY® 20mgn (%) | Teriflunomide 14mgn (%) |
Safety SetIncidence of Treatment-Emergent AESI | PONVORY® 20mg | Teriflunomide 14mg |
Safety SetBradycardia | PONVORY® 20mg4 (0.7%) | Teriflunomide 14mg0 (-) |
Safety SetAtrioventricular block first degree | PONVORY® 20mg3 (0.5%) | Teriflunomide 14mg0 (-) |
Safety SetIntraventricular conduction delay | PONVORY® 20mg2 (0.4%) | Teriflunomide 14mg0 (-) |
Safety SetBundle branch block left | PONVORY® 20mg1 (0.2%) | Teriflunomide 14mg0 (-) |
Safety SetBundle branch block right | PONVORY® 20mg1 (0.2%) | Teriflunomide 14mg0 (-) |
Safety SetSinus arrhythmia | PONVORY® 20mg1 (0.2%) | Teriflunomide 14mg0 (-) |
Safety SetSinus bradycardia | PONVORY® 20mg1 (0.2%) | Teriflunomide 14mg0 (-) |
Safety Set | PONVORY® 20mg0 (-) | Teriflunomide 14mg1 (0.2%) |
Safety Set | PONVORY® 20mg0 (-) | Teriflunomide 14mg1 (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
- Ponvory Summary of Product Characteristics Available at: www.medicines.ie
- 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.
- 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.
