PAH Patients Prefer Yutrepia Over Tyvaso in INSPIRE Study
Yutrepia, an inhaled formulation of treprostinil, was generally well tolerated and improved the quality of life for people with pulmonary arterial hypertension (PAH) in the Phase 3 INSPIRE clinical trial.
The therapy was preferred by nearly all trial participants who switched to it from Tyvaso, an older inhaled treprostinil formulation marketed by United Therapeutics.
Full trial results were detailed in the study, “INSPIRE: Safety and Tolerability of Inhaled LIQ861 (Treprostinil) in Pulmonary Arterial Hypertension (PAH),” published in Pulmonary Circulation. The work was funded by Yutrepia developer Liquidia.
“The INSPIRE study confirms the long-term safety profile, dosing convenience, and tolerability of Yutrepia in PAH patients,” Rajeev Saggar, chief medical officer at Liquidia, said in a press release.
Treprostinil is a vasodilator that prompts blood vessels to relax and widen, thereby lowering blood pressure. Yutrepia, previously called LIQ861, is a dry powder formulation administered using an inhaler device.
The U.S. Food and Drug Administration (FDA) last year granted tentative approval to Yutrepia to treat PAH. The decision means Yutrepia has met all regulatory requirements for approval in terms of safety and effectiveness, but it can’t yet be brought to market due to ongoing litigation with United, which sued Liquidia in 2020 for allegedly infringing on its patents for Tyvaso. A final decision from the FDA is expected later this year.
The FDA’s decision was supported by data from a Phase 3 clinical trial called INSPIRE (NCT03399604). The study enrolled 121 people with PAH; most participants were female, white, and non-Hispanic (mean age, 54).
Among the participants, 55 were on Tyvaso upon entering the study while the other 66 were taking two or fewer other therapies and were treated with Yutrepia in addition to their background therapies.
Participants who switched to Yutrepia from Tyvaso were started on a dose of Yutrepia based on their prior dose of Tyvaso. Those new to Yutrepia were started on a dosage of 26.5 micrograms (mcg) four times daily. Dose increases were permitted based on tolerability and symptom control. By month 12, most were on a dose of at least 79.5 mcg four times daily.
Over the course of the study, with an average follow-up time of about a year, 29 patients (24%) discontinued from the trial, with side effects being the most common reason. The researchers noted that this discontinuation rate compares favorably to studies of other inhaled PAH therapies, where rates higher than 40% have been reported.
Nearly four in five (79.3%) patients reported a side effect related to treatment. Common side effects included cough, headache, upper respiratory tract infection, shortness of breath, dizziness, throat irritation, diarrhea, chest discomfort, fatigue, and the common cold. Most of these were mild or moderate.
The frequency of side effects was markedly lower for patients who switched from Tyvaso (72.7% vs. 84.8%). Patients who switched from Tyvaso also had lower rates of side effects judged moderate or severe (58.1% vs. 81.8%).
Four participants had serious side effects of treatment, including nausea, headache, and throat pain. One of these (who experienced vomiting on the first day of treatment) withdrew from the study. The serious side effects did not lead to Yutrepia discontinuation for the other three.
“While nearly all patients experienced treatment-related [adverse events] consistent with the known side effects seen with inhaled treprostinil therapy … these were mostly mild to moderate in severity and generally did not hinder patients’ ability to continue therapy and titrate to higher doses as needed,” the researchers said, adding that the overall safety profile of Yutrepia “was reassuring, with no unexpected safety concerns noted.”
Measures of physical function, including the six-minute walk distance and WHO functional class, were generally stable or improved over a year on Yutrepia.
Mean scores on the MLHFQ, a measure of health-related quality of life for people with heart disease, improved by more than 10 points after two or four months in the study. Improvements of more than 5 points on the MLHFQ are considered clinically meaningful.
As this was an open-label trial, meaning the participants and the researchers knew what treatment was being given, no definitive conclusions about its effectiveness can be made.
In a week two survey of the trial, all but one (98.2%) of the participants who switched from Tyvaso to Yutrepia said they preferred the RS00 Model 8 dry-powder inhaler device used with Yutrepia over the device they had previously used. The remaining patient reported no preference. All patients preferred or strongly preferred the Yutrepia device at month four.
“The administration of LIQ861 with an easy-to-use dry-powder inhaler offers clinicians an inhaled PAH therapy that may be preferred by many patients based on its added convenience and potential to facilitate a more active lifestyle,” the researchers concluded.
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