Tyvaso (inhaled treprostinil), a therapy developed and marketed by United Therapeutics, is administered as an inhaled solution using a hand-held, portable device.

It was approved by the U.S. Food and Drug Administration (FDA) in 2009 to ease symptoms of pulmonary arterial hypertension (PAH).

In 2021, the medication became the first FDA-approved therapy for the treatment of pulmonary hypertension associated with interstitial lung disease (PH-ILD). Interstitial lung diseases, or ILDs, are a large group of disorders characterized by fibrosis, or scarring, in the lungs.

How Tyvaso works

In PAH, the pulmonary arteries are narrowed. This restricts blood flow and causes abnormally high blood pressure in the lungs. Among other symptoms, the condition makes it more difficult for patients to exercise — or even do common tasks such as climbing stairs.

Prostacyclin, a molecule naturally produced by the body that dilates (widens) blood vessels, is found at abnormally low levels in PAH patients, and is thought to contribute to the development of the disease. This molecule also stops platelets, a type of specialized cell fragment found in the blood, from clumping together and potentially blocking arteries.

The active component of Tyvaso is a synthetic substance that mimics the action of prostacyclin. By binding to receptors on the cells of the arterial walls, it relaxes arterial wall muscles, making it easier for blood to be pumped through the lungs and increasing oxygen transport throughout the body.

Tyvaso in clinical trials

The results from TRIUMPH (NCT00147199), a double-blind Phase 3 clinical trial sponsored by United, were key in the FDA’s 2009 decision to approve Tyvaso for the treatment of PAH. The trial took place at 30 sites in the U.S., Europe, and Israel.

TRIUMPH enrolled 235 PAH patients, who already were taking Tracleer (bosentan) or Revatio (sildenafil citrate), to receive either Tyvaso or a placebo four times daily for 12 weeks (about three months). The trial assessed whether Tyvaso improved patients’ ability to exercise, measured by the six-minute walk test (6MWT), compared with the placebo. As its name suggests, the 6MWT measures the distance (in meters) that a person can walk in six minutes; it is commonly used to assess exercise capacity in people who are able to walk.

After the 12 weeks, patients given Tyvaso were shown to have experienced an improvement of 20 meters (about 66 feet) in the distance walked in six minutes, a significant increase relative to the study’s start. The results were published in the Journal of the American College of Cardiology.

A total of 206 participants who completed the TRIUMPH trial enrolled in an extension study, in which all patients received Tyvaso to test its long-term safety for up to two years. The results of this extension study, published in the Journal of Heart and Lung Transplantation, suggested that Tyvaso had a continued benefit on exercise ability, and that long-term use of the therapy was well-tolerated.

The FDA’s 2021 approval of Tyvaso for PH-ILD was supported by data from a Phase 2/3 clinical trial called INCREASE (NCT02630316), also sponsored by United. The trial enrolled 326 adults with PH-ILD at 97 locations in the U.S. Participants were randomly assigned to receive Tyvaso — inhaled four times daily, up to 12 breaths per session — or a placebo for 16 weeks (about four months).

The results from INCREASE showed that participants treated with Tyvaso experienced an average increase in 6MWT of nearly 21 meters (about 69 feet) over the 16 weeks. In contrast, participants given the placebo experienced a 10-meter (about 33-feet) decrease. Treatment with Tyvaso also significantly lowered levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), which is indicative of improved heart health.

Over the course of the study, significantly fewer participants on Tyvaso than placebo experienced clinical worsening (22.7% vs. 33.1%) or a sudden worsening of symptoms, called an exacerbation (26.4% vs. 38.7%).

Safety data from INCREASE indicated that Tyvaso was well-tolerated. The most common side effects were in line with the medication’s known safety profile and included cough, headache, shortness of breath, dizziness, nausea, fatigue, and diarrhea. Most adverse events (side effects) were mild or moderate in intensity. The rates of serious adverse events were similar among participants given Tyvaso or a placebo (23.3% and 25.8%).

Other information

The most common side effects of Tyvaso include cough, headache, throat irritation and pain, nausea, flushing of the face and neck, dizziness, and fainting.

In October 2017, the FDA approved a third-generation nebulizer for the Tyvaso inhalation system called TD-300/A.

United is developing a potentially more convenient, dry-powder formulation of Tyvaso, known as Tyvaso DPI, in collaboration with MannKind.

Tyvaso has not been approved for marketing in Europe, and in February 2010, United withdrew its application for Tyvaso as an add-on treatment for PAH to the European Medicines Agency.

The company also produces two other approved treprostinil formulations. These are marketed under the brand names Orenitram (extended release oral tablets) and Remodulin (administered as an injection into the vein or under the skin).

Last Updated: April 6, 2021

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