Last updated Jan. 18, 2022, by Marisa Wexler, MS
Fact-checked by Joana Carvalho, PhD
Tyvaso is an inhaled formulation of treprostinil developed and marketed by United Therapeutics. It is administered through a portable, hand-held device that delivers the medicine directly to the lungs.
In 2021, it became the first therapy approved in the U.S. to improve exercise capacity in people with pulmonary hypertension associated with interstitial lung disease (PH-ILD). ILDs comprise idiopathic pulmonary fibrosis (IPF) and other lung fibrotic-related conditions, which are characterized by the thickening and stiffening of lung tissue that lead to fibrosis, or scar tissue formation.
Tyvaso was initially approved in 2009 by the U.S. Food and Drug Administration (FDA) to ease symptoms of pulmonary arterial hypertension (PAH) and to aid exercise capacity for that patient group.
How does Tyvaso work?
IPF is a type of pulmonary fibrosis that has no clear cause. People with late-stage IPF may develop pulmonary hypertension, a condition in which the arteries connecting the heart to the lungs become increasingly narrower, causing a rise in blood pressure.
Treprostinil, Tyvaso’s active ingredient, is a lab-made molecule that mimics the activity of a compound naturally produced in the body, called prostacyclin. Prostacyclin works to widen blood vessels so that blood flows more easily with less pressure. It also helps to prevent blood clots from forming within blood vessels and arteries.
By helping blood vessels to relax and widen, Tyvaso is expected to improve blood circulation while keeping blood pressure low.
Tyvaso in clinical trials
Tyvaso’s approval as a treatment for PH-ILD was supported by data from the Phase 2/3 INCREASE trial (NCT02630316). The trial, sponsored by United, enrolled 326 adults with PH-ILD who were given either Tyvaso or a placebo for 16 weeks (about four months).
The study’s main goal was to evaluate whether Tyvaso — inhaled in up to 12 breaths per treatment session, four times daily — would be superior to placebo at improving patients’ exercise ability, as measured by the six-minute walking distance (6MWD) test. As its name suggests, the 6MWD test measures the distance a person can walk in six minutes; it is commonly used to measure exercise ability in people who are able to walk.
Results showed Tyvaso-treated patients had a significantly higher 6MWD than those given placebo. Treatment also significantly lowered the levels of a marker of heart strain, called NT-proBNP; reduced the occurrence of exacerbations (episodes of sudden disease worsening); and prevented lung function decline.
A randomized and double-blind Phase 3 trial, TETON (NCT04708782), is now enrolling up to 396 adults with IPF, ages 40 and older.
This new trial will assess the safety and efficacy of inhaled Tyvaso, compared with a placebo, in IPF for about one year. Participants will start the study by taking three breaths of the therapy or the placebo, at sessions done four times daily. Use will increase gradually to the target of 12 breaths per session four times daily. Treatment doses may be adjusted for maximum benefit, and those who complete this trial may be invited to continue or start treatment in an open-label extension.
TETON’s main goal is to assess changes in lung function, as seen in forced vital capacity (FVC, a measure of the amount of air a person can forcefully and quickly exhale after a deep breath) from the study’s start to week 52. Secondary goals include time to clinical worsening, time to first acute exacerbation, and changes in patient perceptions, as measured in the K-BILD questionnaire, whose 15 items address breathlessness and activities, psychological well-being, and chest symptoms.
This trial is due to conclude in June 2024, and six clinic visits will be required of enrolled patients.
Tyvaso is administered in four separate treatment sessions each day. The initial dosage is three breaths per session, which should be gradually increased up to nine breaths per session if tolerated. One breath of Tyvaso delivers about 6 micrograms of treprostinil to the lungs.
The most frequent side effects reported in people using Tyvaso include cough, headache, skin flushing, dizziness, nausea, throat irritation and pain, and diarrhea. Treatment with Tyvaso may increase the risk of hypotension (abnormally low blood pressure) or bleeding, especially if taken in combination with other medications that may lower blood pressure or prevent blood clotting, respectively.
United has developed a dry powder inhaled formulation of treprostinil, called Tyvaso DPI. This formulation has shown a more precise dosing profile than standard Tyvaso in healthy volunteers. A Phase 1 study called BREEZE (NCT03950739), which enrolled 51 people with PAH, showed that the two formulations had similar safety and efficacy profiles, though patients were generally more satisfied with Tyvaso DPI. United applied for approval of Tyvaso DPI in the U.S. in 2021; however, an inspection issue at a third-party manufacturing facility delayed the FDA’s decision on the new formulation, which now is expected in 2022.
In addition to its inhaled forms (solution and dry powder), treprostinil is available for PAH patients as an oral formulation called Orenitram and as an injectable known as Remodulin. Both are marketed by United Therapeutics.
The FDA approved the Dreamboat inhalation device (developed by MannKind), a portable and easy-to-use device for dry powder treatments including Tyvaso DPI, in 2014.
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