Multiple sclerosis:
Indications for: PONVORY
Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.
Clinical Trials:
The approval was based on results from a phase 3 head-to-head, randomized trial of Ponvory vs teriflunomide. A total of 1133 patients with relapsing MS, were randomly assigned to either Ponvory 20mg once daily or teriflunomide 14mg once daily.
Results showed that the annualized relapse rate from baseline to Week 108 was reduced by 30.5% for the Ponvory group vs the teriflunomoide group, meeting the trial’s primary endpoint (P =.0003). Moreover, 70.7% of patients treated with Ponvory had no confirmed relapses compared with 60.6% of patients treated with teriflunomide.
Moreover, Ponvory showed superiority in reducing the number of new gadolinium-enhancing (GdE) T1 and T2 lesions compared with teriflunomide by 58.5% and 55.7%, respectively (for both P <.0001).
Adult Dosage:
Swallow whole. Initially 2mg once daily on Days 1 and 2; 3mg once daily on Days 3 and 4; 4mg once daily on Days 5 and 6; 5mg once daily on Day 7; 6mg once daily on Day 8; 7mg once daily on Day 9; 8mg once daily on Day 10; 9mg once daily on Day 11; 10mg once daily on Days 12, 13, and 14. Maintenance: 20mg once daily on Day 15 and thereafter. First dose 4hr monitoring for bradycardia, other abnormalities: see full labeling. Re-initiation of therapy after interruption for ≥4 consecutive doses: start with Day 1 of titration regimen.
Children Dosage:
Not established.
PONVORY Contraindications:
Recent (within the last 6 months) occurrence of: MI, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, Class III/IV heart failure. Presence of Mobitz Type II 2nd- or 3rd degree AV block, sick sinus syndrome, or sino-atrial block, unless paced.
PONVORY Warnings/Precautions:
Increased risk of infections (may be fatal). Obtain recent CBC including lymphocyte count prior to initiation. Consider treatment interruption if serious infection develops. Active infection: do not start until infection resolved. Test for antibodies to varicella zoster virus; if negative, consider immunization before starting ponesimod. Immunosuppressed. Withhold if progressive multifocal leukoencephalopathy (PML) is suspected; discontinue if PML is confirmed. Risk of bradyarrhythmia, AV conduction delays: titration is required for treatment initiation. Obtain ECG prior to initiation to determine if preexisting conduction abnormalities are present. History of cardiac arrest, cerebrovascular disease, uncontrolled hypertension, severe untreated sleep apnea: not recommended; refer to cardiologist if treatment is considered. History of recurrent syncope or symptomatic bradycardia: do benefit/risk assessment; refer to cardiologist if treatment is considered. Monitor BP during treatment. Severe respiratory disease (eg, pulmonary fibrosis, asthma, COPD): perform spirometric evaluation during treatment if clinically indicated. Obtain recent LFTs (within the last 6 months) prior to initiation. Monitor for hepatic dysfunction; discontinue if significant liver injury is confirmed. Moderate or severe hepatic impairment (Child-Pugh class B and C): not recommended. Perform periodic skin exam (esp. with risk factors); monitor for suspicious skin lesions and evaluate if observed. Diabetes, history of uveitis: increased risk of macular edema. Perform ophthalmic exam of fundus, including the macula, prior to initiation, and if any change in vision occur during therapy. Monitor for severe increase in disability after treatment discontinuation. Elderly. Pregnancy. Advise females of reproductive potential to use effective contraception during and for 1 week after discontinuation. Nursing mothers.
PONVORY Classification:
Sphingosine 1-phosphate receptor modulator.
PONVORY Interactions:
Concomitant antineoplastic, immunosuppressant or immune-modulating therapies may increase risk of immunosuppression; use caution when switching from long-acting immunotherapies; caution for 1–2 weeks after discontinuing ponesimod. Initiation after treatment with alemtuzumab: not recommended. Concomitant QT prolonging drugs (eg, quinidine, procainamide, amiodarone, sotalol): risk of torsades de pointes; refer to cardiologist if treatment is considered. Concomitant β-blockers, digoxin, diltiazem, verapamil during initiation may be associated with severe bradycardia or heart block; refer to cardiologist if treatment is considered. Avoid live attenuated vaccines during and for 1–2 weeks after discontinuing ponesimod; may have suboptimal response. Antagonized by strong CYP3A4 and UGT1A1 inducers (eg, rifampin, phenytoin, carbamazepine): concomitant use not recommended. Concomitant phototherapy with UV-B radiation or PUVA-photochemotherapy: not recommended.
Adverse Reactions:
Upper respiratory tract infection, hepatic transaminase elevation, hypertension, UTI, dyspnea, dizziness; macular edema, basal cell carcinoma/melanoma, decreased pulmonary function; rare: posterior reversible encephalopathy syndrome (discontinue if suspected).
Drug Elimination:
After a single IV administration, the total clearance of ponesimod is 3.8 L/hour. The elimination half-life after oral administration is approximately 33 hours. Following a single oral administration of 14C-ponesimod, 57% to 80% of the dose was recovered in feces (16% as unchanged ponesimod), and 10% to 18% in urine (no unchanged ponesimod).
Generic Drug Availability:
NO
How Supplied:
Starter Pack (2mg, 3mg, 4mg, 5mg, 6mg, 7mg, 8mg, 9mg, 10mg)—14; Tabs (20mg)—30
