Switching from the approved Tyvaso (inhaled treprostinil) nebulizer to Tyvaso DPI — an investigational dry-powder formulation — is safe, effective, and likely more convenient for people with pulmonary arterial hypertension (PAH), top-line data from the Phase 1 BREEZE trial show.
These positive findings also were supported by data from a study involving healthy volunteers. That data showed that United Therapeutics‘ new breath-powered inhaler led to treatment exposures comparable to those achieved with its existing Tyvaso nebulizer.
“We are pleased with these results, which demonstrate the safety, tolerability, and pharmacokinetic profiles of treprostinil administered as Tyvaso DPI,” Leigh Peterson, PhD, United’s vice president of product development, said in a press release. Of note, pharmacokinetics are a therapy’s absorption, distribution, metabolism, and excretion by the body.
Detailed data from both studies will be presented at upcoming scientific conferences and published in peer-reviewed journals.
Results from these and other trials will support United’s submission of a new drug application to the U.S. Food and Drug Administration (FDA) in April. That application will seek Tyvaso DPI’s approval for PAH and pulmonary hypertension associated with interstitial lung disease (lung scarring).
The company plans to use a rare pediatric disease priority review voucher to shorten the FDA’s review period to eight months, rather than the standard one year.
“If approved, we expect Tyvaso DPI will provide a major advancement in the delivery of inhaled treprostinil therapy, offering convenience benefits compared to our existing Tyvaso nebulizer,” Peterson said.
Treprostinil — a vasodilator that widens lung blood vessels, lowering blood pressure — was approved by the FDA in 2002 for the treatment of PAH. It is commercially available as Tyvaso in an inhaled form, as Orenitram in an oral form, and as Remodulin in an injectable form, all marketed by United.
While Tyvaso is administered as an inhaled solution using a hand-held, portable device, Tyvaso DPI combines a dry powder inhaled formulation of treprostinil with MannKind’s Dreamboat inhalation device. Dreamboat, approved by the FDA in 2014, is a small, portable, and easy-to-use device to deliver treatments through dry powder.
The company’s goal is to simplify dosing and offer PAH patients a more convenient and tolerable treprostinil treatment option. In collaboration with MannKind, United is developing Tyvaso DPI, formerly known as Treprostinil Technosphere, also for the treatment of pulmonary hypertension associated with interstitial lung disease.
The Phase 1 BREEZE study (NCT03950739) evaluated Tyvaso DPI’s safety, pharmacokinetics, and effectiveness in 51 PAH patients previously on a stable regimen of Tyvaso Inhalation Solution (six to 12 breaths four times a day).
Participants received Tyvaso DPI at the corresponding dose of Tyvaso Inhalation Solution for three weeks. All of the individuals underwent safety and pharmacokinetics assessments, as well as a six-minute walk test — to assess exercise capacity — before starting Tyvaso DPI and after the three-week treatment period.
At the same time, they completed questionnaires regarding satisfaction/preference for inhaled devices and patient-reported PAH symptoms and impact.
Top-line results showed that the transition from Tyvaso Inhalation Solution to Tyvaso DPI was safe and well-tolerated, with most adverse events (side effects) being mild to moderate. There were no occurrences of treatment-related serious adverse events. Moreover, the severity and frequency of the side effects were consistent with those reported in previous inhaled treprostinil studies involving PAH patients.
A total of 49 participants (96%) completed the treatment phase and the latest assessments. After three weeks of treatment, these patients showed improved exercise capacity, reduced patient-reported PAH symptoms and impact, and greater overall satisfaction with the Tyvaso DPI treatment relative to the Tyvaso nebulizer.
Pharmacokinetics data are still being analyzed by the company.
All participants who completed the three-week treatment chose to enter an extension phase, in which they will receive Tyvaso DPI until the study ends or the therapy becomes commercially available.
Notably, improvements seen in patients’ exercise capacity were sustained in the extension phase through the data cut-off date, United stated in the release.
The company also shared data from a second trial that assessed the pharmacokinetics, safety, and tolerability of three doses of Tyvaso DPI and three doses of Tyvaso Inhalation Solution in 36 healthy volunteers.
The results showed that participants’ exposure to treprostinil was comparable between Tyvaso DPI and Tyvaso Inhalation Solution at each dose level. However, Tyvaso DPI resulted in less treatment exposure variability between volunteers, suggesting a more precise dosing profile relative to the Tyvaso nebulizer.
Also, Tyvaso DPI’s safety profile was consistent with that reported on previous studies with Tyvaso Inhalation Solution.
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