Ponvory now available for treatment of relapsing remitting MS

Janssen is introducing Ponvory (ponesimod) for the treatment of adults with relapsing remitting multiple sclerosis (MS). Ponesimod is the fourth orally-administered sphingosine 1-phosphate (S1P) receptor modulator to be marketed for treatment of MS in Canada, following fingolimod (Gilenya, generics), ozanimod (Zeposia) and siponimod (Mayzent).1,2 Ponesimod binds to S1P1 receptors on lymphocytes. This prevents lymphocyte exit from lymph nodes, which reduces the number of lymphocytes in peripheral blood. The mechanism by which ponesimod acts in MS may involve reduction of lymphocyte migration into the central nervous system.1 Read: Montreal doc and research team receive $1 million grant for AI multiple sclerosis research Dosage Ponvory will be supplied in a 14-day initiation pack containing 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg and 10 mg tablets, and in a 28-day maintenance pack containing 20 mg tablets. Starting ponesimod treatment results in a transient decrease in heart rate and atrioventricular conduction delays. Therefore, patients must be uptitrated slowly using the 14-day initiation pack: 2 mg once daily on Days 1 and 2; 3 mg once daily on Days 3 and 4; 4 mg once daily on Days 5 and 6; 5 mg once daily on Day 7; 6 mg once daily on Day 8; 7 mg once daily on Day 9; 8 mg once daily on Day 10; 9 mg once daily on Day 11, and 10 mg once daily on Days 12, 13 and 14. Then patients should proceed to the maintenance dosage of 20 mg once daily. If treatment is interrupted at any point, follow the dosing instructions provided in the product monograph.1 Ponesimod tablets may be taken with or without food. Tablets should be swallowed whole.1 After the first dose of ponesimod, patients should be monitored for four hours for signs and symptoms of bradycardia, with a minimum of hourly pulse and blood pressure measurements. A longer duration of monitoring may be required depending on heart rate/electrocardiogram (ECG) findings (consult product monograph for details).1 Read: Latest clinical guidelines and statements: ALS, COVID-19 vaccine, multiple sclerosis and more Adverse effects The most common adverse effects of ponesimod are alanine aminotransferase (ALT) increases, nasopharyngitis, upper respiratory tract infection, fatigue, dyspnea and dizziness. More serious potential adverse effects include sinus bradycardia, reduced heart rate and an increase in blood pressure. An ECG is required in all patients before starting therapy, to determine whether preexisting conduction abnormalities are present.1 Elevations of liver transaminases (AST/ALT) may occur; liver transaminases and bilirubin levels should be measured within the first three months of therapy, and periodically thereafter or as clinically indicated.1 Ponesimod causes a dose-dependent reduction in peripheral lymphocyte count; therefore, it may increase the risk of infections. Cases of severe herpes viral infection have been reported. The drug has the potential to cause cryptococcal infections and progressive multifocal leukoencephalopathy. It also increases the risk of macular edema. Ponesimod is contraindicated during pregnancy.1 Read: Zeposia: new oral treatment for relapsing-remitting multiple sclerosis Drug interactions Ponesimod must be used cautiously with drugs that reduce heart rate (e.g., beta-blockers, calcium channel blockers) due to a possible additive effect. Drugs that prolong the QTc interval (e.g., Class Ia antiarrhythmics [procainamide, disopyramide]) and Class III antiarrhythmics [e.g., amiodarone, sotalol]) should be avoided or used with caution. Ponesimod is not recommended to be used with strong CYP3A and UGT1A1 inducers (e.g., rifampin, phenytoin, carbamazepine). The drug is contraindicated in patients who are immunocompromised while on antineoplastic, immune-modulating or immunosuppressive therapies.1 A recent review concluded that ponesimod reduced relapse rates and lesion accumulation, but not disability progression, compared to teriflunomide (Aubagio) (a modestly effective comparator) in one randomized double-blind trial. As with other S1P modulators, ponesimod may increase the risk of infection and cause bradycardia and atrioventricular conduction delays. How it compares with other S1P modulators in efficacy and safety is unknown.2 References 1. Janssen Inc. Ponvory (ponesimod tablets) product monograph. Toronto, ON: April 28, 2021. https://pdf.hres.ca/dpd_pm/00060843.PDF (accessed November 15, 2021). 2. Anon. Ponesimod (Ponvory) for multiple sclerosis. Med Lett Drugs Ther 2021; 63:123-5.

Ponvory now available for treatment of relapsing remitting MS

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