Long-term Tyvaso DPI treatment safe, effective in PAH: Trial data
Patient satisfaction with dry powder inhaler was also improved
Long-term treatment with Tyvaso DPI safely and effectively leads to increases in exercise capacity in adults with pulmonary arterial hypertension (PAH). Tyvaso DPI is a dry powder, inhaled form of treprostinil.
Patient satisfaction was also improved with Tyvaso DPI compared with Tyvaso, which is a nebulized, inhaled formulation of treprostinil.
These are the results of the optional extension phase (OEP) of the Phase 1 BREEZE clinical trial (NCT03950739) that tested the safety, efficacy, and convenience of changing from Tyvaso to Tyvaso DPI. Previous BREEZE top-line data supported Tyvaso DPI’s approval in the U.S. for PAH and pulmonary hypertension associated with interstitial lung disease.
“The availability of a more portable device with improved tolerability and comparable efficacy can facilitate shared decision-making and support an individualized approach to therapy selection,” researchers wrote.
The study, “BREEZE Optional Extension Phase: Long-Term Safety and Efficacy of Treprostinil Dry Powder Inhaler (Tyvaso DPI) in Pulmonary Arterial Hypertension,” was published in the journal Respiratory Medicine. It was sponsored by United Therapeutics, which markets both Tyvaso and Tyvaso DPI.
Treprostinil relaxes, widens bllod vessels, lowering blood pressure
In PAH, the vessels that carry blood to the lungs become narrower, increasing blood pressure. As a result, the heart needs to work harder to pump blood, resulting in symptoms such as severe shortness of breath. In advanced disease stages, people with PAH may experience heart failure.
Treprostinil prompts blood vessels to relax and widen, lowering blood pressure and allowing the heart to pump blood more easily. It is available in inhaled, oral, under-the-skin, and into-the-bloodstream formulations.
Tyvaso was the first inhaled form of treprostinil to be approved for PAH. It comes as a liquid, which a nebulizer turns into vapor for inhalation. Tyvaso DPI, which uses a dry powder in an inhaler, “was developed as a small, portable, low-maintenance device to improve patient experience,” the researchers wrote.
This type of device “reduces the amount of pressure the patient must generate and provides greater consistency in the amount of drug delivered,” the researchers wrote. It is therefore “preferred … in patients with cardiopulmonary diseases,” they added.
The BREEZE trial assessed the safety and efficacy of switching from a stable regimen of Tyvaso (six to 12 breaths four times a day) to a corresponding dose of Tyvaso DPI in 51 adults with PAH. Participants self-administered the medication at their assigned dose four times a day for three weeks.
Top-line results demonstrated that the treatment transition was generally safe and tolerable. Tyvaso DPI treatment was also associated with significant improvements in exercise capacity, as assessed with the six-minute walk test (6MWT), reductions in patient-reported symptoms, and higher satisfaction compared to Tyvaso.
Participants experienced increase in exercise capacity with long-term treatment
All of the 49 participants who completed the three-week treatment period chose to enter the trial’s OEP, where they continued Tyvaso DPI treatment until it became commercially available.
OEP participants’ mean age was 56, and 84% were women. They received Tyvaso DPI for a median of 107 weeks (about two years) and up to 201 weeks (nearly four years) across all BREEZE phases. During the OEP, the therapy dose could be increased to each patient’s maximally tolerated dose.
Results showed that participants experienced an increase in their exercise capacity with long-term Tyvaso DPI treatment. Between one and two years of treatment, there was an increase in the proportion of patients experiencing an improvement of at least 30 meters (32% vs. 37%) and of at least 50 meters (16% vs. 26%).
Among people with available 6MWT data at two years, gains in the number of steps observed at one and two years were accompanied by increases in Tyvaso DPI dosage.
Patient satisfaction with the DPI device was overwhelmingly positive while drug-related adverse events were infrequen.
In addition, available responses of the PAH-SYMPACT questionnaire, a patient-reported measure of PAH symptoms and impacts, showed no significant differences in scores after switching to Tyvaso DPI.
“There was no loss of symptom management compared to while on [Tyvaso] inhalation solution,” the researchers wrote.
Satisfaction with Tyvaso DPI was higher than with Tyvaso, with most (88%) of the 21 responders at the last study visit strongly agreeing they were satisfied with the inhaler.
“At the end-of-study visit, 100% of patients said they agreed or strongly agreed that [Tyvaso] DPI is a favorable size and is easy to hold, travel with, and set up,” the researchers wrote.
In terms of safety, cough and headache were the most common adverse events possibly related to treatment, with each occurring in 14% of participants. There weren’t any treatment-related serious adverse events. There also wasn’t a clear relationship between dosage and side effect occurrence. Adverse events led to study discontinuation in five participants.
“Patient satisfaction with the DPI device was overwhelmingly positive while drug-related adverse events were infrequent,” the researchers wrote. “The long-term outcomes of the BREEZE OEP demonstrated that [Tyvaso] DPI was a safe and tolerable treatment option for patients with PAH that may provide long-term maintenance of clinical stability.”
Among the study’s limitations, the team noted the lack of a control group and the fact that it is unclear how well these results translate to patients with different demographics.
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