By: Jack (Hongkai) Bao, Staff Editor
On December 21st 2015, the FDA approved selexipag (Uptravi®), marketed by Actelion Pharmaceuticals US, Inc. for the treatment of pulmonary arterial hypertension (PAH) in adults.1
Selexipag offers a newer treatment alternative for PAH, the conventional therapy of which originally included vasodilators such as Epoprostenol (Flolan®) and Treprostinil (Remodulin®) as well as Phosphodiesterase-5 Inhibitors (PDE-5i) such as Sildenafil (Revatio®) and Tadalafil (Adcirca®). Selexipag however, is an IP (prostacylin) receptor agonist. It mimics the effects of prostacyclin, which is a major product of cyclooxygenase that causes potent vasodilation.1
This vasodilation is necessary in patients with PAH. PAH is a condition characterized by high blood pressure affecting the arteries of an individual’s lungs. This condition can occur when arteries or capillaries in the lungs become occluded, forcing the right side of the heart to work harder to pump blood to the lungs. Ultimately, PAH can cause the right side of the heart to fail and can lead to fatal events.2 PAH is usually asymptomatic in the first few months or years of progression. However as it continues, more serious symptoms can manifest, such as dyspnea while exercising or at rest, fatigue, dizziness, chest pain, and peripheral edema in the ankles and legs.2 PAH can also lead to a number of complications such as cor pulmonale (right-sided heart failure), thrombosis and eventual pulmonary embolism, arrhythmias, and hemorrhage in the lungs, which can lead to hemoptysis.2 By vasodilating the pulmonary arteries, selexipag allows blood to flow more easily, reducing the workload of the heart.
The GRIPHON trial studied the long-term effects of selexipag on morbidity, mortality, as well as its general safety and efficacy in patients.3 Patients had a 50:50 chance of receiving either selexipag or placebo, and patients on selexipag were titrated up to the maximum tolerable dose of 200 µg to 1600 µg twice daily.4 Of the 1,156 patients studied, selexipag had a significant impact on morbidity and mortality by reducing the risk of events occurring by 40% when compared to placebo.4 The main adverse effects observed during the GRIPHON trial included nausea, diarrhea, myalgia, arthralgia, flushing, and pain in extremities.4
Selexipag was given orphan drug designation, which means that the manufacturer received the typical incentives for developing and manufacturing drugs for rare disease states such as PAH.1 The introduction of selexipag into the market will offer an alternative for patients suffering from PAH which has been proven to be safe and efficacious.
- FDA approves new orphan drug to treat pulmonary arterial hypertension. U.S. Food and Drug Administration. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm478599.htm. Updated 12/22/2015. Accessed 01/03/2015.
- Mayo Clinic Staff. Diseases and conditions: pulmonary hypertension. Mayo Clinic. http://www.mayoclinic.org/diseases-conditions/pulmonary-hypertension/basics/treatment/con-20030959. Published 03/27/2013. Accessed 01/04/2016.
- McLaughlin V, Channick R, Chin K, et al. Effect of Selexipag on morbidity/mortality in pulmonary arterial hypertension: results of the GRIPHON study [abstract]. J Am Coll Cardiol. 2015;65(10_S). doi:10.1016/S0735-1097(15)61538-8.
- 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. doi:10.1056/NEJMoa1503184.