What is Ponvory (Ozanimod)?

From the Guidelines

Ponvory (ponesimod) is an oral medication approved for treating relapsing forms of multiple sclerosis (MS) in adults, including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS, with a recommended dosage of 20 mg once daily after a 14-day titration schedule. It belongs to the class of sphingosine 1-phosphate (S1P) receptor modulators and works by preventing immune cells from leaving lymph nodes, which reduces the number of these cells reaching the central nervous system where they could cause damage 1.

Key Considerations for Treatment

• The typical dosage involves a 14-day titration schedule starting at 2 mg daily and gradually increasing to the maintenance dose of 20 mg once daily.
• Common side effects include headache, upper respiratory tract infections, elevated liver enzymes, and temporary heart rate reduction after the first dose.
• Patients should receive all necessary vaccines at least 4 weeks before starting treatment, and women of childbearing potential should use effective contraception during and for 1 week after stopping Ponvory due to potential risks to a developing fetus.
• Before starting treatment, patients need baseline assessments including blood tests, eye examination, and cardiac evaluation since Ponvory can affect heart rhythm, liver function, and may increase the risk of infections.

Monitoring and Precautions

• Liver enzymes and function should be assessed periodically during treatment, and treatment should be interrupted if transaminases are confirmed to be >5 times the ULN and discontinued in the event of liver injury 1.
• Ophthalmic evaluations should be performed regularly in patients with a history of uveitis, macular oedema, or diabetes to minimize the risk of macular oedema.
• Patients should be counselled to inform their physician of any new prescribed medications to allow for a review of potential drug-drug interactions.

Special Considerations

• Ponvory treatment can be continued during COVID-19 infection if warranted, as post hoc analyses of clinical trial data showed that most ozanimod-treated patients with UC or MS who contracted COVID-19 had non-serious infections and recovered without sequelae 1.
• An increased risk of cutaneous malignancies has been reported with some S1P receptor modulators, and patients with active malignancies should not initiate ozanimod treatment.

From the FDA Drug Label

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. PONVORY may cause serious side effects, including: Infections. PONVORY can increase your risk of serious infections that can be life-threatening and cause death. PONVORY is a prescription medicine that is used to treat relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

Ponvory is a medication used to treat relapsing forms of multiple sclerosis (MS) in adults, including:

• Clinically isolated syndrome
• Relapsing-remitting disease
• Active secondary progressive disease It is a sphingosine 1-phosphate receptor modulator that can cause serious side effects, including infections. Key points to consider when taking Ponvory:
• It can increase the risk of serious infections
• It can cause slow heart rate when starting treatment
• It is not known if Ponvory is safe and effective in children
• Women who can become pregnant should use effective birth control during treatment with Ponvory and for 1 week after stopping treatment 2, 2

From the Research

Overview of Ponvory

• Ponvory, also known as ponesimod, is an orally administered selective sphingosine-1-phosphate (S1P) receptor 1 (S1P1) agonist 3.
• It is developed by the Janssen Pharmaceutical Companies of Johnson & Johnson for the treatment of multiple sclerosis (MS) 3.

Approval and Indication

• Ponesimod was recently approved in the USA for the treatment of relapsing forms of MS 3.
• It has received a positive CHMP opinion in the EU for this indication 3.
• Ponesimod is classified as a disease modifying treatment (DMT) for MS 4.

Efficacy and Safety

• Clinical studies have shown that ponesimod prevents relapse in patients with relapsing-remitting MS (RRMS) and has superior efficacy compared with teriflunomide 4.
• Common adverse effects associated with ponesimod include nasopharyngitis, upper respiratory tract infections, headache, high blood pressure, and liver dysfunction 4.
• Rare but serious adverse effects associated with ponesimod include dyspnea, bradyarrhythmias, atrioventricular conduction delays, and macular edema 4.

Comparison with Other S1P Receptor Modulators

• Ponesimod has been compared with other S1P receptor modulators, including fingolimod, ozanimod, and siponimod, in terms of clinical management considerations 5.
• The results of a discrete choice experiment (DCE) showed that ponesimod had the highest overall MCDA score, followed by siponimod, fingolimod, and ozanimod 5.
• Having fewer drug-drug interactions contributed most to the overall scores, followed by having no first-dose observations, the shortest immune system recovery time, and not interacting with foods high in tyramine 5.

Practical Considerations

• Clinicians should choose the drug based on disease type, history, and concomitant medications for each patient 6.
• Continued and regular monitoring of patients during treatment is recommended, with attention to cardiac monitoring guidelines, screening for macular edema and cutaneous malignancies before starting treatment 6.