Transition to dry powder inhaled treprostinil safe, tolerable for patients with PAH
Transition from nebulized inhaled treprostinil to a dry powder inhaled formulation was safe, well tolerated and led to significant improvements in clinical and patient-reported outcomes in patients with pulmonary arterial hypertension.
Final results of the BREEZE study and its ongoing optional extension phase were recently published in Pulmonary Circulation.
The dry powder formulation of treprostinil studied in BREEZE is in development with a reusable breath-powered dry powder inhaler (Tyvaso DPI, United Therapeutics Corporation) and is undergoing review by the FDA. If approved, Tyvaso DPI is expected to provide a more convenient method of administration compared with nebulized treprostinil, according to a company press release.
The BREEZE study enrolled 51 adults with PAH (mean age, 55.9 years; 84.3% women) on a stable treprostinil inhalation solution regimen (Tyvaso, United Therapeutics) who transitioned to the dry powder formulation. The primary outcome was the safety and tolerability of treprostinil inhalation powder during a 3-week treatment phase in patients currently treated with treprostinil inhalation solution. Secondary outcomes included change in 6-minute walk distance, device preference and satisfaction assessed using the Preference Questionnaire for Inhaled Treprostinil Devices (PQ-ITD) and patient-reported PAH Symptoms and Impact questionnaire.
The majority of patients were on dual background PAH therapies at baseline.
Most patients (96%) completed the 3-week treatment phase.
Researchers reported no serious adverse events related to the study drug. Most adverse events were mild to moderate and were consistent with those observed in other inhaled treprostinil studies in patients with PAH, according to the researchers. Mild adverse events were reported in 53% and moderate adverse events in 12% during the treatment phase. The most common adverse events reported were cough, headache and dyspnea.
Three weeks after transitioning to the dry powder formulation, 6-minute walk distance improved 11.5 m compared with baseline (P = .0217); overall satisfaction, on the PQ-ITD, improved (P < .0001); and physical PAH impacts (P = .0438) and cognitive/emotional PAH impacts (P = .0048) improved at week 3 as well as physical PAH impacts (P = .0438) at week 11, according to responses to the PAH Symptoms and Impact questionnaire, the researchers reported.
Systemic exposure between nebulized treprostinil and dry powder inhaled treprostinil was comparable between the two formulations. Between-subject variability for area under the curve and peak serum concentration parameters was similar across dose levels for each formulation. However, variability of AUC and peak serum concentration was two- to three-fold lower for the dry powder formulation, according to the release.
Participants in the BREEZE study could continue in an optional extension phase. All participants who completed the treatment phase (49 of 51) elected to continue in the optional extension phase. As of the July 2021 data cutoff for the publication in Pulmonary Circulation, 17 patients had reached 51 weeks of Tyvaso DPI use and 39 patients were still participating in the optimal extension phase, but not all had reached the 51-week visit at the cutoff, according to information in the release.
During the optional extension phase, none of the serious adverse events were determined to be related to the study treatment. Mild adverse events were reported in 61% and moderate adverse events in 49% of patients during the optional extension phase. The most common adverse events included those observed during the treatment phase as well as low incidences of arthralgia, diarrhea, dizziness and pneumonia, according to the results. During the optional extension phase, most patients either maintained or increased their study dose from baseline. Additionally, improvements in 6-minute walk distance were sustained for up to week 51 at the data cutoff date, according to the release.
The new study builds on earlier data presented at the European Respiratory Society International Congress in 2021. The optional extension phase is ongoing, according to the release.
United Therapeutics has submitted a new drug application to the FDA seeking approval of Tyvaso DPI for treatment of adults with PAH and interstitial lung disease-associated PAH, according to the release.
“If approved, I believe Tyvaso DPI could represent a very exciting addition to the treatment paradigm for the PAH population,” Leslie A. Spikes, MD, associate professor of pulmonary and critical care medicine at the University of Kansas Medical Center, Kansas City, Kansas, said in the release. “The ease of use, portability and ability to titrate the dose with Tyvaso DPI should have a beneficial impact on patient compliance and persistence and could result in improved exercise ability.”
- United Therapeutics announces the publication of Tyvaso DPI BREEZE clinical and long-term data in the journal Pulmonary Circulation. Published April 6, 2022. Accessed April 7, 2022.