Ponesimod

Ponesimod is a S1P receptor 1 modulator that binds with high affinity to S1P receptor 1. Ponesimod blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood.

• PONVORY is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. PONVORY is a sphingosine 1-phosphate receptor modulator indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.ICD-10: G35

• PONVORY is contraindicated in patients who: In the last 6 months, have experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III or IV heart failure [see Warnings and Precautions ( 5.2 )] Have presence of Mobitz type II second-degree, third-degree AV block, sick sinus syndrome, or sino-atrial block, unless patient has a functioning pacemaker [see Warnings and Precautions ( 5.2 )] In the last 6 months, experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failure ( 4 ) Presence of Mobitz type II second-degree, third-degree AV block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker ( 4 )contraindicated

Assessments are required prior to initiating PONVORY ( 2.1 ) Titration is required for treatment initiation ( 2.2 ) The recommended maintenance dosage is 20 mg taken orally once daily ( 2.2 ) First-dose monitoring is recommended for patients with sinus bradycardia, first- or second-degree [Mobitz type I] atrioventricular (AV) block, or a history of myocardial infarction or heart failure ( 2.3 ) 2.1 Assessments Prior to First Dose of PONVORY Before initiation of treatment with PONVORY, assess the following: Cardiac Evaluation Obtain an electrocardiogram (ECG) to determine whether preexisting conduction abnormalities are present. In patients with certain preexisting conditions, advice from a cardiologist should be sought and first-dose monitoring is recommended [see Dosage and Administration ( 2.3 ) and Warnings and Precautions ( 5.2 )] . Complete Blood Count Obtain a recent (i.e., within the last 6 months or after discontinuation of prior MS therapy) complete blood count (CBC), including lymphocyte count [see Warnings and Precautions ( 5.1 )] . Determine whether patients are taking drugs that could slow heart rate or atrioventricular (AV) conduction [see Warnings and Precautions ( 5.2 ) and Drug Interactions ( 7.2 , 7.3 )] . Liver Function Tests Obtain recent (i.e., within the last 6 months) transaminase and bilirubin levels [see Warnings and Precautions ( 5.4 )] . Ophthalmic Evaluation Obtain a baseline evaluation of the fundus, including the macula, near the start of treatment with PONVORY [see Warnings and Precautions ( 5.8 )] .

Infections : PONVORY may increase the risk of infections. Obtain a complete blood count (CBC) before initiating treatment. Monitor for infection during treatment and for 1-2 weeks after discontinuation. Do not start PONVORY in patients with active infection. ( 5.1 ) Bradyarrhythmia and Atrioventricular Conduction Delays : PONVORY may result in a transient decrease in heart rate; titration is required for treatment initiation. Check an electrocardiogram (ECG) to assess for preexisting cardiac conduction abnormalities before starting PONVORY. Consider cardiology consultation for conduction abnormalities or concomitant use with other drugs that decrease heart rate. ( 5.2 , 7.2 , 7.3 ) Respiratory Effects : May cause a decline in pulmonary function. Assess pulmonary function (e.g., spirometry) if clinically indicated. ( 5.3 ) Liver Injury : Discontinue if significant liver injury is confirmed. Obtain liver function tests before initiating PONVORY. ( 5.4 ) Increased Blood Pressure (BP) : Monitor BP during treatment. ( 5.5 ) Cutaneous Malignancies : Skin examination prior to or shortly after the start of treatment and periodically is recommended. Suspicious skin lesions should be evaluated. ( 5.6 ) Fetal Risk : Women of childbearing potential should use effective contraception during and for 1 week after stopping PONVORY. ( 5.7 ) Macular Edema : Increases the risk of macular edema. Obtain a baseline evaluation of the fundus, including the macula, near the start of treatment with PONVORY.

The following serious adverse reactions are described elsewhere in labeling: Infections [see Warnings and Precautions ( 5.1 )] Bradyarrhythmia and Atrioventricular Conduction Delays [see Warnings and Precautions ( 5.2 )] Respiratory Effects [see Warnings and Precautions ( 5.3 )] Liver Injury [see Warnings and Precautions ( 5.4 )] Increased Blood Pressure [see Warnings and Precautions ( 5.5 )] Cutaneous Malignancies [see Warnings and Precautions ( 5.6 )] Fetal Risk [see Warnings and Precautions ( 5.7 )] Macular Edema [see Warnings and Precautions ( 5.8 )] Posterior Reversible Encephalopathy Syndrome [see Warnings and Precautions ( 5.9 )] Unintended Additive Immunosuppressive Effects From Prior Treatment With Immunosuppressive or Immune-Modulating Therapies [see Warnings and Precautions ( 5.10 )] Severe Increase in Disability After Stopping PONVORY [see Warnings and Precautions ( 5.11 )] Immune System Effects After Stopping PONVORY [see Warnings and Precautions ( 5.12 )] Most common adverse reactions (incidence at least 10%) are upper respiratory tract infection, hepatic transaminase elevation, and hypertension. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Vanda Pharmaceuticals, Inc. at 833-933-9331, FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Hepatic Impairment: PONVORY is not recommended in patients with moderate or severe hepatic impairment (Child-Pugh class B and C). ( 8.6 ) 8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of PONVORY in pregnant women. In animal studies, administration of ponesimod during pregnancy produced adverse effects on development, including embryo lethality and fetal malformations, in the absence of maternal toxicity. In rats and rabbits, visceral and skeletal malformations occurred at clinically relevant maternal ponesimod exposures (see Data) . The receptor affected by ponesimod (sphingosine-1-phosphate receptor 1) has been demonstrated to have an important role in embryogenesis, including vascular and neural development. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data When ponesimod (0, 1, 10, or 40 mg/kg/day) was orally administered to pregnant rats during the period of organogenesis, increased incidences of fetal malformations primarily involving the limbs (syndactyly and ectrodactyly) and cardiovascular system (including ventricular septal defects) were observed at all but the lowest dose tested.

Metabolism

Following ponesimod oral dosing, C max and AUC increased approximately dose-proportionally in the dose-range studied (1-75 mg). Steady-state levels are approximately 2.0- to 2.6-fold greater than with a single dose, and are achieved following 3 days of administration of the maintenance dose of ponesimod.

Symptoms and Signs In patients with overdosage of PONVORY, especially upon initiation/reinitiation of treatment, it is important to observe for signs and symptoms of bradycardia as well as AV conduction blocks, which may include overnight monitoring. Regular measurements of pulse rate and blood pressure are required, and ECGs should be performed [see Warnings and Precautions ( 5.2 , 5.5 ) and Clinical Pharmacology ( 12.2 )] . Treatment There is no specific antidote to ponesimod. Neither dialysis nor plasma exchange would result in meaningful removal of ponesimod from the body. The decrease in heart rate induced by PONVORY can be reversed by atropine. In the event of overdose, PONVORY should be discontinued, and general supportive treatment given until clinical toxicity has been diminished or resolved. It is advisable to contact a poison control center to obtain the latest recommendations for the management of an overdose.

• Mar 18, 2021NDANDA213498Vanda Pharms Inc

1. 1Product Dose Omission Issue4113%
2. 2Fatigue247.5%
3. 3Dizziness165.0%
4. 4Dyspnoea165.0%
5. 5Covid-19134.0%
6. 6Headache123.7%
7. 7Drug Ineffective103.1%
8. 8Hypoaesthesia103.1%
9. 9Multiple Sclerosis Relapse92.8%
10. 10Nausea92.8%
11. 11Multiple Sclerosis82.5%
12. 12Pain82.5%
13. 13Somnolence82.5%
14. 14Therapy Interrupted82.5%
15. 15Hypersensitivity72.2%

The 10 most recently updated of 21 ClinicalTrials.gov registrations naming Ponesimod as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Open Label Study to Investigate the Safety and Efficacy of Ponesimod in Moderate-to-Severe Chronic Plaque Psoriasis
  Recruiting · Phase 3 · Interventional · 300 enrolled · Vanda Pharmaceuticals
  NCT07362017updated 2026-06-11
• A Study to Learn More About The Safety of Diroximel Fumarate (VUMERITY®) in Participants Who Took it During Pregnancy And About the Health of Their Babies
  Active not recruiting · Observational · 1,178 enrolled · Biogen
  NCT05688436updated 2026-06-04
• Traditional Versus Early Aggressive Therapy for Multiple Sclerosis Trial
  Active not recruiting · Interventional · 900 enrolled · Johns Hopkins University
  NCT03500328updated 2025-10-14
• Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS
  Active not recruiting · Phase 4 · Interventional · 800 enrolled · The Cleveland Clinic
  NCT03535298updated 2025-08-28
• A Clinical Trial Evaluating the Safety and Efficacy of Myelin-peptide Loaded tolDC as Treatment for MS
  Withdrawn · Phase 2 · Interventional · 0 enrolled · University Hospital, Antwerp
  NCT06715605updated 2025-08-17
• Long-term Extension to Study AC-058B301 to Investigate Safety, Tolerability and Disease Control of Ponesimod 20 mg in Patients With Relapsing Multiple Sclerosis
  Completed · Phase 3 · Interventional · 877 enrolled · Actelion
  NCT03232073updated 2025-06-22
• A Study of Ponesimod in Healthy Adult Participants
  Completed · Phase 1 · Interventional · 28 enrolled · Janssen Pharmaceutica N.V., Belgium
  NCT05552196updated 2025-04-27
• A Study of Ponesimod in Healthy Adult Participants Receiving Propranolol at Steady State
  Completed · Phase 1 · Interventional · 52 enrolled · Janssen Pharmaceutica N.V., Belgium
  NCT03882255updated 2025-04-27
• Oral Ponesimod Versus Teriflunomide In Relapsing MUltiple Sclerosis
  Completed · Phase 3 · Interventional · 1,133 enrolled · Actelion
  NCT02425644updated 2025-03-30
• Clinical Study to Investigate the Long-term Safety, Tolerability, and Efficacy of Ponesimod in Patients With Relapsing-remitting Multiple Sclerosis
  Completed · Phase 2 · Interventional · 353 enrolled · Actelion
  NCT01093326updated 2025-03-30

Frequently asked questions

How does Ponesimod work?

Ponesimod is a S1P receptor 1 modulator that binds with high affinity to S1P receptor 1. Ponesimod blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood.

What is Ponesimod used for?

According to FDA labeling, Ponesimod carries indications including: PONVORY is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. PONVORY is a sphingosine 1-phosphate receptor modulator indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Ponesimod?

Ponesimod is classified as Sphingosine-1-phosphate (S1P) receptor modulators, Sphingosine 1-phosphate Receptor Modulator, Sphingosine 1-Phosphate Receptor Modulators.

What are the brand names for Ponesimod?

Ponesimod is marketed under brand names including Ponvory.

What are the contraindications for Ponesimod?

Ponesimod labeling lists contraindications including: PONVORY is contraindicated in patients who: In the last 6 months, have experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III or IV heart failure [see Warnings and Precautions ( 5.2 )] Have presence of Mobitz type II second-degree, third-degree AV block, sick sinus syndrome, or sino-atrial block, unless patient has a functioning pacemaker [see Warnings and Precautions ( 5.2 )] In the last 6 months, experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failure ( 4 ) Presence of Mobitz type II second-degree, third-degree AV block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker ( 4 ). Always consult the full prescribing information and a clinician.