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Transcript
Uptravi® - Selexipag Manufacturer: Actelion FDA Approval Date: December 21, 2015 Uptravi® - Selexipag Objectives • At the end of this presentation participants will be able to: 1. Appropriately recommend Uptravi® - (Selexipag) 2. Effectively educate patients on the purpose, proper use and potential adverse effects of Uptravi® - (Selexipag) Uptravi® - Selexipag Clinical Application • Indications: • Treatment of pulmonary arterial hypertension (PAH), WHO Group I, to delay disease progression and reduce risk of hospitalization for PAH • Place in therapy: • As monotherapy or in combination with other classes of PAH medications Uptravi® [package insert]. Uptravi® - Selexipag Clinical Application • Contraindications: • None • Black Box warnings • None • Warnings & Precautions: • If pulmonary edema occurs, consider pulmonary veno-occlusive disease (PVOD). If PVOD confirmed, discontinue use of selexipag Uptravi® [package insert]. Uptravi® - Selexipag Clinical Application • Pregnancy: • No studies in pregnant women • No relevant clinical effects in animal reproductive studies • Lactation: • Unknown if excreted in human breast milk • Recommend discontinuation of selexipag if nursing Uptravi® [package insert]. Uptravi® - Selexipag Drug Facts • Pharmacology: • Prostacyclin IP receptor agonist • Vasodilator Uptravi® [package insert]. Uptravi® - Selexipag Drug Facts • Pharmacokinetics: A Time to peak (selexipag): 1-3 hours Time to peak (metabolite): 3-4 hours ~30% lower Cmax, and delayed time to Tmax in presence of food D Highly bound (99%) to plasma proteins M Hydrolysis to yield active metabolite, then metabolism catalyzed by CYP3A4 and CYP2C8 E Terminal t ½ (selexipag): 0.8-2.5 hours; terminal t ½ (active metabolite): 6.2-13.5 hours Uptravi® [package insert]. Uptravi® - Selexipag Drug Interactions • Drug Interactions • Avoid concomitant administration with strong CYP2C8 inhibitors (e.g. gemfibrozil) as this results in increased exposure to selexipag and active metabolite Uptravi® [package insert]. Uptravi® - Selexipag Adverse Effects • Common Adverse Effects: (selexipag%)[placebo%] • Headache (65%) [32%] • Diarrhea (42%) [18%] • Jaw pain (26%) [6%] • Nausea (33%) [18%] • Serious Adverse Effects: • none Uptravi® [package insert]. Uptravi® - Selexipag Monitoring Parameters • Efficacy Monitoring: • 6-minute walk distance • WHO functional class • Toxicity Monitoring: • Unmanageable adverse effects Uptravi® [package insert]. Uptravi® - Selexipag Prescription Information • Dosing: • Initial: 200 mcg PO BID • Titration: Increase dose by 200 mcg PO BID at weekly intervals to maximum tolerated dose • Maximum dose: 1600 mcg PO BID • Cost: – $13,000 per 30 days Uptravi® [package insert]. Medpagetoday.com 1/6/16 Uptravi® - Selexipag Griphon study – selexipag for pulmonary arterial hypertension Uptravi® - Selexipag Literature Review • Purpose: Efficacy and safety of selexipag in patients with pulmonary arterial hypertension who were either: • Not receiving therapy at baseline or • Receiving one or two therapies for the disease at baseline Sitbon O, et al. N Engl J Med. 2015;373(26):2522-33. Uptravi® - Selexipag Literature Review • Study Design: • Multi-center, randomized, double-blind, placebo-controlled, event driven, phase 3 study • 1156 total patients, 181 centers, 39 countries, December 2009-May 2013 • Treatment arms • Selexipag • Placebo Sitbon O, et al. N Engl J Med. 2015;373(26):2522-33. Uptravi® - Selexipag Literature Review • Inclusion: • 18-75 years old • PVR 5 wood units, 6 minute walking distance (6MWD) 50-450 m • No treatment for PAH • Treatment with endothelin receptor antagonist, PDE5 inhibitor, or both at a dose stable for at least 3 months Sitbon O, et al. N Engl J Med. 2015;373(26):2522-33. Uptravi® - Selexipag Literature Review • Primary Endpoint: • Time to event analysis: • Composite of death from any cause or complication related to PAH up to the end of the treatment period (7 days after the last intake of selexipag or placebo) Sitbon O, et al. N Engl J Med. 2015;373(26):2522-33. Uptravi® - Selexipag Literature Review • Secondary Endpoints: • Change in 6MWD from baseline to week 26 • Absence of worsening of WHO functional class from baseline to week 26 • Death due to PAH or hospitalization for worsening of PAH up to the end of treatment period and death from any cause up to the end of the study • Safety: Adverse effects and lab abnormalities Sitbon O, et al. N Engl J Med. 2015;373(26):2522-33. Uptravi® - Selexipag Literature Review Baseline Characteristics Age Female WHO Functional Class III Average 6 minute walk distance Background PAH treatments 48 years 80% 69% 353 meters 20.4% none 14.7% ERA 32.4% PDE5i 32.5% ERA + PDE5i Sitbon O, et al. N Engl J Med. 2015;373(26):2522-33. Uptravi® - Selexipag Literature Review • Results: • 123 patients experienced primary end point • Side effects with highest risk of discontinuation: • Headache • Diarrhea • Nausea • More common in dose adjustment phase Sitbon O, et al. N Engl J Med. 2015;373(26):2522-33. Uptravi® - Selexipag Literature Review Placebo Selexipag P-value 41.6 27 <0.001 18.7 13.6 17.2 6.6 23.5 17.8 0.003 - 9.0 m + 4.0 m 0.003 74.9 77.8 0.28 Primary Endpoint All events Hospitalization for worsening PAH Disease progression Secondary Endpoint All events 6MWD change from baseline No worsening in WHO functional class Sitbon O, et al. N Engl J Med. 2015;373(26):2522-33. Uptravi® - Selexipag Literature Review • Conclusions: • Selexipag lowers rate of death or complication related to PAH vs. placebo • No difference in mortality between groups • Addition of selexipag to baseline regimen of two meds gave benefits consistent with overall treatment effect • Similar efficacy regardless of dose range Sitbon O, et al. N Engl J Med. 2015;373(26):2522-33. Uptravi® - Selexipag Summary • Uptravi®, Selexipag, is an oral prostacyclin receptor agonist for pulmonary arterial hypertension (PAH) • Should not be used with strong CYP2C8 inhibitors • Administered at 200 mcg BID and titrated on a weekly basis to the highest tolerated dose or the max dose of 1600 mcg BID • Most common side effects include; headache, diarrhea, jaw pain and nausea • Can use in combination with PAH medications (PDE-5 inhibitors and endothelin receptor antagonists) but should not be used with another prostacyclin agonist Uptravi® - Selexipag References 1. www.uptravi.com 2. Uptravi package insert. Actelion. Dec. 2015. 3. Sitbon O, Channick R, Chin KM, et al. Selexipag for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2015;373(26):2522-33.