Ponvory From Janssen Pharmaceuticals, Inc

The FDA has approved Ponvory (ponesimod; Janssen) for the treatment of relapsing forms of multiple sclerosis (MS) in adults, including active secondary progressive disease, clinically isolated syndrome, and relapsing-remitting disease.¹

MS occurs when immune cells damage or destroy myelin. Common symptoms include problems with balance, bladder, bowel, and vision, along with dizziness, fatigue, numbness, tingling, vertigo, and weakness.²

Pharmacology and Pharmacokinetics

Ponvory is a sphingosine 1-phosphate (S1P) receptor modulator. How its mechanism treats MS remains unknown but may involve the reduction of lymphocyte migration into the central nervous system.

Steady-state plasma concentration is observed after 3 days of oral maintenance dosing. Ponvory reaches maximum plasma concentration 2 to 4 hours after an oral dose and displays an elimination half-life of approximately 33 hours.¹

Dosage and Administration

The following clinical assessments are required before beginning treatment with Ponvory: cardiac evaluation, complete blood count, confirmation of antibodies to varicella zoster virus, evaluation of current or prior medications with immune system effects, liver function tests, ophthalmic evaluation, and vaccination status. After assessments are completed, treatment with Ponvory begins with a 14-day once-daily oral dose titration that is supplied in a starter pack. The titration schedule consists of 2 mg on days 1 and 2, 3 mg on days 3 and 4, 4 mg on days 5 and 6, 5 mg on day 7, 6 mg on day 8, 7 mg on day 9, 8 mg on day 10, 9 mg on day 11, and 10 mg on days
12, 13, and 14. Beginning on day 15, the recommended maintenance dose is 20 mg orally once daily. Ponvory should be swallowed whole with or without food. First-dose monitoring is recommended for patients with first- or second-degree (Mobitz type I) atrioventricular (AV) block, a history of heart failure or myocardial infarction, or sinus bradycardia.¹

Clinical Trials

Ponvory was evaluated in an active-controlled, double-blind, parallel group, randomized superiority study in patients with relapsing forms of MS. The length of treatment was 108 weeks. Participants received either once-daily Ponvory, beginning with a 14-day dose titration, or teriflunomide (Aubagio) 14 mg once daily. The primary end point was the annualized relapse rate, which was statistically significantly lower in the participants who received Ponvory than in those who received teriflunomide. Additionally, the numbers of new gadolinium-enhancing T1 lesions and enlarging or new T2 lesions from baseline to week 108 were statistically significantly lower in participants who received Ponvory than in those who received teriflunomide.^1,2

Contraindications, Warnings, and Precautions

The use of Ponvory is contraindicated in patients who have experienced Class III/IV heart failure, decompensated heart failure requiring hospitalization, myocardial infarction, stroke, transient ischemic attack, or unstable angina within the past 6 months. Ponvory is also contraindicated in patients with Mobitz type II second-degree, third-degree AV block, or sick sinus syndrome, unless the patient has a functioning pacemaker.

Ponvory may increase the risk of infections. Patients should be monitored for infection during treatment and for 1 to 2 weeks after discontinuation, and patients with an active infection should not begin treatment. Ponvory may result in a decline in pulmonary function and a transient decrease in heart rate. Ponvory should be discontinued if significant liver injury occurs. Blood pressure should
be monitored during treatment with Ponvory. Periodic skin examination is recommended to monitor for cutaneous malignancies. Women of childbearing age should use effective contraception during treatment and for 1 week after stopping Ponvory. S1P receptor modulators, including Ponvory, have been associated with an increased risk of macular edema, and this risk is greater in patients with diabetes mellitus and a history of uveitis. Administration of live attenuated vaccines during treatment with Ponvory and for up to 1 to 2 weeks after discontinuation should be avoided. Ponvory should not be taken with strong CYP3A4 and UGT1A1 inducers. Ponvory should not be used in patients with moderate or severe hepatic impairment.

The most common adverse reactions are hepatic transaminase elevation, hypertension, and upper respiratory tract infection.¹

Monica Holmberg, PharmD, BCPS, is a pharmacist and Pharmacy Times® contributor.

REFERENCES

1. Ponvory. Prescribing information. Janssen; 2021. Accessed May 25, 2021. https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/PONVORY-pi.pdf
2. Janssen announces U.S. FDA approval of PONVORY (ponesimod), an oral treatment for adults with relapsing multiple sclerosis proven superior to Aubagio (teriflunomide) in reducing annual relapses and brain lesions. News release. Janssen. March 19, 2021. Accessed May 25, 2021. https://www.janssen.com/janssen-announces-us-fda-approval-ponvory-ponesimod-oral-treatment-adults-relapsing-multiple