Uptravi (selexipag) is a medicine, marketed by Actelion, that can help to slow the progression of pulmonary arterial hypertension (PAH), one of the most common complications of systemic scleroderma. It was approved by the U.S. Food and Drug Administration (FDA) to treat PAH in 2015.
How Uptravi works
PAH is characterized by constricted blood vessels in the lungs, resulting in elevated blood pressure. PAH treatments have long focused on the prostacyclin pathway. Prostacyclin is a naturally occurring hormone and a potent vasodilator, meaning it causes blood vessels to widen. It does this by binding to the prostacyclin receptor and activating it. Activation of the prostacyclin receptor is anti-inflammatory and anti-proliferative, meaning it inhibits cell growth.
Uptravi targets the prostacyclin receptor to activate vasodilation, which helps widen blood vessels and lower high blood pressure.
Uptravi in clinical trials
A number of Phase 1 clinical trials were performed, and found that Uptravi was safe and well-tolerated by healthy volunteers.
The medication’s safety and effectiveness in patients with PAH was assessed in a Phase 3 clinical trial (NCT01106014) called GRIPHON. This randomized, double-blind, and placebo-controlled trial enrolled 1,156 adult patients, including 170 people who disease was associated with systemic scleroderma.
Participants were randomly assigned to a treatment or placebo group. Those receiving the medicine started with 200 micrograms of Uptravi twice daily, and then received weekly increments up to 1,600 micrograms or their highest tolerated dose. On average, patients were treated with Uptravi for 1.4 years.
The study measured safety and efficacy as time until hospitalization associated with disease progression, the start of oxygen therapy, the need for a lung transplant, or death.
Results showed that Uptravi reduced the number of PAH-associated hospitalizations and the risk of death and morbidity (associated conditions) by 41 percent in PAH patients with connective tissue diseases. Those in the treatment arm were also able to walk 39 feet longer than patients receiving placebo in a test of exercise ability.
Uptravi’s benefits in terms of physical activity is being studied in a Phase 4 clinical trial (NCT03078907) currently recruiting PAH patients in the U.S., Europe, and the U.K. Participants will wear a wrist device that collects data on their daily physical activities, and are required report on their symptoms throughout the study. The trial is expected to finish in June 2019.
Another Phase 3 study (NCT03187678) assessed whether it is safe for PAH patients to switch from oral Uptravi to Uptravi injected into the bloodstream, particularly important to those who are hospitalized and unable to swallow. Results for this trial, which ended in June 2018, are not yet available.
A newly starting Phase 2 open-label study (NCT03492177) will evaluate the safety and tolerability of increasing doses of Uptravi in pediatric PAH patients, ages 2-18. Information on test sites is not yet available, and the trial is not yet open for recruitment.
The most common side effects of Uptravi include headaches, diarrhea, jaw pain, nausea, muscle pain, rash, joint pain, low red blood cell counts, and loss of appetite.
The safety of Uptravi in children with PAH (age 18 and younger) is not yet established.
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