Switching to Orenitram may benefit some PAH patients on Uptravi

Study of real-world data show transition is safe, may reduce risk

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A doctor hands a glass of water to a patient who is taking an oral medication.

Switching to Orenitram, an oral formulation of treprostinil, appears safe and may benefit some patients with pulmonary arterial hypertension (PAH) who are not responding well to Uptravi (selexipag) or are experiencing side effects from such treatment.

That’s according to data from a small group of 10 patients who took part in ADAPT (NCT03045029), a registry that recorded the effects of the real-world use of Orenitram over 1.5 years (78 weeks). The registry was sponsored by United Therapeutics, which markets Orenitram.

“This multicenter, real-world, observational analysis demonstrated that patients can be safely transitioned from [Uptravi] to oral [Orenitram],” the researchers wrote.

Moreover, the team noted that “patients demonstrated clinical benefit after transitioning,” with three individuals showing a reduction on a risk calculator and five maintaining the same risk category from the study’s start to the last follow-up.

The data were described in “Safety and efficacy of transitioning from selexipag to oral treprostinil in pulmonary arterial hypertension: Findings from the ADAPT registry,” a study published in Pulmonary Pharmacology and Therapeutics.

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Patients switched from Uptravi due to poor response, side effects

A narrowing of the pulmonary arteries, which take blood from the heart to the lungs, can lead to high blood pressure in these blood vessels. The condition, known as pulmonary arterial hypertension or PAH, reduces the amount of oxygen that can get into the lungs, causing symptoms that make exercise difficult.

Uptravi is an approved medication that works in a way similar to prostacyclin, a naturally occurring molecule that lowers blood pressure by causing the blood vessels to widen. The therapy can be given orally or via an into-the-vein or intravenous infusion.

Just as with any other medication, some patients may not respond well to Uptravi or may experience side effects that make them stop using it. But what happens when they switch to another medication, such as Orenitram, is not well described.

“In the setting of unsatisfactory clinical response or tolerability issues while on [Uptravi], there is little data on clinical benefit, safety, or strategies on transitioning to oral [Orenitram],” the researchers wrote.

To learn more, a team in the U.S. now studied the switch from Uptravi to Orenitram, a medication that also mimics the way prostacyclin works. Orenitram, given as a tablet, is used to delay disease progression and improve exercise capacity.

In the setting of unsatisfactory clinical response or tolerability issues while on [Uptravi], there is little data on clinical benefit, safety, or strategies on transitioning to oral [Orenitram].

The study’s data came from the ADAPT registry, which followed patients who were started on Orenitram sustained-release tablets taken by mouth three times a day. Of the 179 patients in ADAPT, 10 had transitioned from Uptravi.

Their mean age was 61.8 and seven (70%) were women. Five (50%) had idiopathic PAH, meaning its cause was unknown. In four (40%), PAH was associated with connective tissue disease, and in one (10%), it was associated with exposure to a drug or toxin.

Seven individuals (70%) were switched to Orenitram because they did not respond well to Uptravi or saw their disease get worse, while three (30%) did not tolerate the medication well. Overall, the patients had received Uptravi for a median of 66 weeks, or just longer than 15 months; their median total daily dose was 2,800 micrograms (mcg).

Four of the patients (40%) were started on Orenitram as soon as they stopped Uptravi, which they had taken at a median total daily dose of 1,000 mcg. Orenitram was started at a median dose of 0.375 milligrams (mg); at the last follow-up visit, its median total daily dose was 9 mg.

In the other six patients (60%), the switch was done by gradually reducing Uptravi’s dose while increasing that of Orenitram over a median six weeks; this is called cross-titration. Before the switch, Uptravi’s median total daily dose was 3,200 mcg; at the last follow-up, that of Orenitram was 15 mg.

Five patients, or 50% in all, showed clinical improvement after the switch.

That means they met at least two of three varying criteria. One was an increase in the distance walked in six minutes, a standard assessment, by at least 10% or 30 meters (about 98 feet). Another was a classification under World Health Organization guidelines of functional class I or II. The final criteria was a decrease in NT-proBNP or BNP, a marker of heart disease, by at least 30%.

According to a risk calculator called REVEAL Lite 2, three individuals (30%) improved their risk category and five patients (50%) maintained it after the switch. Two (20%) saw an increase in risk even after the switch.

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Small study, but largest data set to date, per researchers

At the time of switching, three patients reported diarrhea, headache, and an unspecified side effect. None of the three patients who had stopped taking Uptravi due to side effects were intolerant to Orenitram.

After switching, “the most bothersome side effects reported for the ten patients were headache, diarrhea, and pain in extremities,” the researchers wrote.

One patient was admitted to the hospital due to fainting and low blood pressure, or hypotension, about five weeks into treatment. This was possibly related to Orenitram, according to the team. However, “the patient recovered and was discharged from the hospital,” they noted.

All patients transitioned off Uptravi in an outpatient setting without the need for medications other than oral treprostinil to bridge the potential gap between one therapy and the next, which other researchers had suggested “due to safety concerns,” the scientists wrote.

In addition to its oral formulation, treprostinil is available as a solution for continuous infusion or injection under the skin (subcutaneous administration) or into a vein (intravenous administration), for which it is sold as Remodulin, or as generics. Treprostinil also is available as Tyvaso, a solution for inhalation.

While the number of patients was small, the researchers noted that “this was the largest data set on [Uptravi] to [Orenitram] transitions.”

The team concluded that the study’s findings support the use of Orenitram “as a safe and clinically appropriate treatment option.”

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