Tyvaso is an inhaled formulation of treprostinil developed and marketed by United Therapeutics. It is administered through a portable and hand-held device that delivers the medicine directly to the lungs.
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) in 2021. ILDs comprise idiopathic pulmonary fibrosis (IPF) and other lung fibrotic-related conditions, which are characterized by the thickening and stiffening of lung tissue that leads to the formation of scars (fibrosis).
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 this 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 PH, 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
The Phase 2/3 INCREASE trial (NCT02630316) supported Tyvaso’s approval as an PH-ILD treatment.
The study assessed and compared the therapy’s safety and efficacy to that of a placebo in 326 adults with PH-ILD over 16 weeks (about four months).
Its main goal was to evaluate whether Tyvaso — inhaled in up to 12 breaths per treatment session, four times daily — would be superior at improving patients’ exercise ability comparatively with the placebo. This was evaluated by the six-minute walking distance (6MWD) test, which measures the distance a person can walk in that time.
Results showed Tyvaso-treated patients treated had a significant mean increase of 21 meters (about 96 feet) in the 6MWD test compared with those on a 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.
The Phase 1 BREEZE trial (NCT03950739) evaluated the safety and effectiveness of a dry powder inhaled formulation of treprostinil, called Tyvaso DPI, in 51 people with PAH who were previously being receiving an inhaled solution of Tyvaso.
After three weeks, 49 patients showed improved exercise capacity, fewer patient-reported symptoms, and more satisfied with Tyvaso DPI in comparison to the inhaled version. Patients who completed the treatment and joined an extension phase to continue taking Tyvaso DPI also experienced improvements in exercise capacity.
A second trial focused on assessing the pharmacokinetics — the movement of a therapy into, through, and out of the body — of three doses of Tyvaso DPI and three doses of Tyvaso inhalation solution in 36 healthy volunteers showed that Tyvaso DPI had a more precise dosing profile.
Based on data from these two trials, United Therapeutics filed an application requesting FDA approval of Tyvaso DPI to also treat PH-ILD in April 2021. That request is under agency review.
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 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 April 2024, and six clinic visits will be required of enrolled patients.
The most frequent side effects reported in people using Tyvaso include cough, headache, shortness of breath, skin flushing, dizziness, nausea, throat irritation and pain, fatigue, and diarrhea.
Tyvaso was designated an orphan drug as a potential IPF treatment by the FDA in 2020. This designation is given to therapies with the potential to significantly improve treatment for rare diseases, and includes benefits for the developer like tax credits and FDA support for clinical trials. If a therapy is approved, it also grants its developer seven years of marketing exclusivity in the U.S.
In addition to its inhaled forms (solution and dry powder), treprostinil is available for PAH patients as an oral formulation called Orenitram, and in as 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.
Last updated: May 4, 2021
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