Tyvaso (treprostinil) inhalation solution - 2 indications

Scroll down for more information on each indication:

• for the treatment of pulmonary arterial hypertension; approved July 2009
• for the treatment of pulmonary hypertension associated with interstitial lung disease; approved March of 2021

General Information

Tyvaso is a prostacyclin analogue. It directs vasodilation of pulmonary and systemic arterial vascular beds and inhibits platelet aggregation.

Tyvaso is specifically indicated for the following:

• for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability
• for the treatment of pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability

Tyvaso is suppled as a solution designed for oral inhalation. Tyvaso should be dosed in 4 separate, equally spaced treatment sessions per day, during waking hours. The treatment sessions should be approximately 4 hours apart.

Initial Dosage
Therapy should begin with 3 breaths of Tyvaso (18 mcg of treprostinil), per treatment session, 4 times daily. If 3 breaths are not tolerated, reduce to 1 or 2 breaths and subsequently increase to 3 breaths, as tolerated.

Maintenance Dosage
Dosage should be increased by an additional 3 breaths at approximately 1-2 week intervals, if tolerated, until the target dose of 9 breaths (54 mcg of treprostinil) is reached per treatment session, 4 times daily. If adverse effects preclude titration to target dose, Tyvaso should be continued at the highest tolerated dose. The maximum recommended dosage is 9 breaths per treatment session, 4 times daily.

Mechanism of Action

Tyvaso is a prostacyclin analogue. It directs vasodilation of pulmonary and systemic arterial vascular beds and inhibits platelet aggregation.

Side Effects

Adverse events associated with the use of Tyvaso may include, but are not limited to, the following:

• Cough
• Headache
• Throat Irritation
• Nausea
• Flushing
• Syncope

Indication 1 - for the treatment of pulmonary arterial hypertension

approved July 2009

Clinical Trial Results

The FDA approval of Tyvaso for PAH was based on the results of a 12-week, randomized, double-blind, placebo-controlled multi-center study, dubbed TRIUMPH. This trial enrolled 235 clinically stable subjects who were receiving either bosentan or sildenafil for at least three months prior to study initiation. The subjects received either placebo or Tyvaso in four daily treatment sessions with a target dose of 9 breaths (54 mcg) per session over the course of the 12-week study. The primary efficacy endpoint was the change in six-minute walk distance (6MWD) relative to baseline at 12 weeks. The subjects receiving Tyvaso had a placebo-corrected median change from baseline in peak 6MWD of 20 meters at Week 12.

Indication 2 - for the treatment of pulmonary hypertension associated with interstitial lung disease

approved March of 2021

Clinical Trial Results

The FDA approval of Tyvaso for PAH-ILD was based on the multicenter, randomized, double-blind, placebo-controlled, 16-week, parallel-group INCREASE study in 326 adult patients with World Health Organization (WHO) Group 3 PH-ILD. The patients were enrolled at 93 centers and randomized to inhaled Tyvaso (n=163) four times daily or placebo (n=163). The primary efficacy endpoint was the change in six-minute walk distance (6MWD) measured at peak exposure from baseline to Week 16. Results showed that Tyvaso significantly increased 6MWD by 31 meters as analyzed using the Mixed Model Repeated Measurement. When analyzed using a pre-specified worst case imputation for missing data and Hodges-Lehmann estimate, Tyvaso improved 6MWD by 21 meters relative to placebo over the same time period. The benefits of Tyvaso were observed across subgroups, including etiology and severity of PH-ILD, age group, gender, baseline hemodynamics, and dose group.