Ponesimod Trade names Ponvory
Pregnancy category AU: D
Routes of administration By mouth
Pharmacokinetic data It has Metabolism 2 main metabolites Elimination half-life 31–34 hrs
Excretion Feces (57–80%, 26% unchanged), urine (10–18%)[8]
Ponesimod, sold under the brand name Ponvory, is a medication for the treatment of multiple sclerosis.
It is a sphingosine-1-phosphate receptor modulator.
The most common side effects include upper respiratory tract infection, hepatic transaminase elevation, and hypertension.
Ponesimod is indicated for the treatment of relapsing forms of multiple sclerosis including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.
QT prolongation is detectable but was considered to be too low to be of clinical importance in a study.
Like fingolimod, which is already approved for the treatment of multiple sclerosis, ponesimod blocks the sphingosine-1-phosphate receptor.
It prevents lymphocytes from leaving lymph nodes, thereby reducing the number of lymphocytes in peripheral blood.
Its mechanism may help reduce lymphocyte migration into the central nervous system, although the exact therapeutic mechanism in MS is not fully understood.
Ponesimod is selective for subtype 1 of this receptor, S1P1.
Phase II clinical trial including 464 multiple sclerosis patients, ponesimod treatment resulted in fewer new active brain lesions than placebo, measured during the course of 24 weeks.
In a Phase II clinical trial including 326 patients with psoriasis, 46 or 48% of patients had a reduction of at least 75% Psoriasis Area and Severity Index (PASI) score compared to placebo in 16 weeks.
In a Phase III randomised, double-blind clinical trial of 1133 adult patients with relapsing multiple sclerosis, those under ponesimod treatment showed a 30% reduction in annual relapse rate and a significantly reduced number of new inflammatory lesions on brain MRI by 56% compared to those taking teriflunomide.
It is indicated for the treatment of relapsing forms of multiple sclerosis (MS) in adults, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.
It is administered orally and requires a titration period before reaching the maintenance dosage of 20 mg once daily.
Its pharmacodynamics include a dose-dependent reduction in peripheral blood lymphocyte count, with significant effects observed at doses starting from 5 mg..
The greatest reduction in lymphocyte count occurs approximately 6 hours post-dose.
Ponesimod significantly reduced the annualized relapse rate (ARR) and the number of new or enlarging T2 lesions on MRI.
Ponesimod’s superiority has been demonstrated over teriflunomide, a commonly used disease-modifying therapy (DMT) for MS.
Ponesimod’s pharmacokinetic profile includes rapid absorption with peak plasma concentrations reached within 2-4 hours post-dose and a terminal half-life of approximately 33 hours.
It has a quick onset of action and rapid reversibility of its immunosuppressive effects upon discontinuation.
The drug’s selectivity for the S1P receptor 1 and its short half-life are advantageous in managing potential adverse effects, such as bradyarrhythmias and lymphopenia, which are mitigated by a gradual up-titration schedule.
Adverse effects:
Common adverse effects in studies were temporary bradycardia, usually at the beginning of the treatment, dyspnoea and increased liver enzymes.
Common adverse effects associated with ponesimod include nasopharyngitis, upper respiratory tract infections, headache, hypertension, and liver enzyme elevations.
Serious but less frequent adverse effects include dyspnea, bradyarrhythmias, atrioventricular conduction delays, and macular edema.