Switching treatment from United Therapeutics’ Tyvaso (inhaled treprostinil) to Actelion’s Uptravi (oral selexipag) is safe and considered convenient by patients with pulmonary arterial hypertension (PAH), a Phase 3b study reports.
The study, “Safety and tolerability of transition from inhaled treprostinil to oral selexipag in pulmonary arterial hypertension: Results from the TRANSIT-1 study” was published in the Journal of Heart and Lung Transplantation.
Uptravi is an oral prostacyclin receptor agonist that acts as a vasodilator, causing blood vessels to relax and dilate. The therapy was approved in the U.S. in 2015 as a twice-daily oral treatment for PAH to slow disease progression and reduce the risk of hospitalization.
According to the team, patients treated with “more burdensome inhaled therapies” that also target the prostacyclin pathway, such as Tyvaso, may consider changing to a more convenient treatment such as Uptravi, an oral therapy.
Actelion therefore conducted a clinical study to address whether such a transition would be feasible, safe, and considered convenient by PAH patients.
The trial, called TRANSIT-1 (NCT02471183) was an open-label, Phase 3b study taking place at 12 centers across the U.S. The study’s goals were to test the tolerability and safety of the transition, investigate the effects of Uptravi on PAH severity and patients’ exercise capacity, and compare patient satisfaction with the treatment change.
The transition period took 16 weeks, during which inhaled Tyvaso was tapered off over eight weeks, while oral Uptravi was titrated to the maximum tolerated dose for each patient, until week 12 (up to a maximal of 1,600 mcg twice a day). After this period, patients remained on the maximum dose of Uptravi until week 16. After that, those who wished could remain on treatment with Uptravi until it became commercially available.
To evaluate whether patients remained clinically stable during and after the therapy transition, researchers assessed PAH severity and progression using the WHO classification, the six-minute walk distance (6MWD) test to assess exercise capacity, and assessment of the serum levels of NT-proBNP, a marker of right heart failure in PH. All these parameters were assessed at the study’s start and at the end of the 16-week transition.
Patients were also asked to complete a questionnaire at week 16 to address whether the change in medication had improved their satisfaction with treatment.
A total of 34 PAH patients were enrolled, most of whom were women (82.4%), who had been on Tyvaso for an average of 3.3 years. Most patients (73.5%) were classified as WHO category 2 at the study’s start, meaning they had no symptoms at rest but felt uncomfortable and had shortness of breath with ordinary activities.
At week 16, nearly all patients (94.1%) had stopped receiving Tyvaso; most (28 patients out of 32) had completed a full transition to Uptravi (sustained treatment transition). After the study’s end, 31 patients continued treatment with commercial Uptravi.
Sustained treatment transition was defined as being on Uptravi at week 16, without any interruptions for at least eight days, and having discontinued Tyvaso after the eighth week.
Overall, the therapy switch was well-tolerated; the most frequent adverse events were typical of prostacyclin-based therapies, including headache, diarrhea, and jaw pain. The severity was mild for 5.9%, moderate for 70.6%, and severe for 20.6% of the patients. Most of these side effects appeared during the transition phase.
Three patients stopped Uptravi because of adverse events. One experienced pain and fainting (syncope), another had pain in the extremities, and a third interrupted treatment after week 16 because of shortness of breath and fainting.
Most patients “remained stable during the follow-up period based on clinical measures,” researchers wrote. WHO classification of disease severity remained unchanged in 23 patients (67.6%) and improved in nine. In 73.5% of the patients, 6MWD was either maintained or increased, and no significant change in NT-proBNP levels was noticed.
In the survey, PAH patients noted that changing to Uptravi “simplified their treatment regimen compared with inhaled treprostinil,” researchers said. Furthermore, the patients reported that the therapy improved the convenience and overall satisfaction with treatment without changing its effectiveness.
The study demonstrated that switching from Tyvaso to Uptravi “was generally successful, safe, and comparable” to other studies evaluating PAH therapy transitioning, researchers concluded.
The team also emphasized that Uptravi treatment “was associated with greater patient-rated convenience.”