Tyvaso Improves Lung Function in PH-ILD Patients, New Trial Data Show

Treatment with Tyvaso (inhaled treprostinil) can improve lung function in people with pulmonary hypertension associated with interstitial lung disease (PH-ILD), new data from a completed Phase 2/3 clinical trial show.

These data were presented at CHEST 2020, the annual meeting of the American College of Chest Physicians, in the poster, “The Impact of Inhaled Treprostinil on Patient Lung Function: Results from the INCREASE Study.”

“We are encouraged by the favorable impact on lung function in PH-ILD patients receiving Tyvaso versus placebo in the INCREASE study, as well as preclinical evidence demonstrating the antifibrotic activity of treprostinil,” Leigh Peterson, PhD, vice president of product development at United Therapeutics, which markets the treatment, said in a press release.

ILDs are a group of lung diseases characterized by scarring (fibrosis) within the lungs. Often, ILD is complicated by pulmonary hypertension, or abnormally high pressure in the lung’s blood vessels. Currently, no medications are approved to treat PH-ILD in the U.S.

Tyvaso contains treprostinil, which is a vasodilator — a medication that causes blood vessels to widen, lowering the pressure within them. It is administered as an inhaled solution using a hand-held, portable device.

Tyvaso is approved in the U.S. to treat pulmonary arterial hypertension (PAH; WHO Group 1 PH), but not PH-ILD (Group 3).

A supplemental new drug application, supported by trial results, requests that Tyvaso also be approved for PH patients with ILD. It is currently under review by the U.S. Food and Drug Administration, with a decision expected by April.

INCREASE, a Phase 2/3 clinical trial (NCT02630316), evaluated the safety and efficacy of Tyvaso (inhaled four times daily, up to 12 breaths per session) in people with PH-ILD compared with a placebo.

The trial enrolled 326 adults with PH-ILD. Among participants, the most common causes of PH-ILD were idiopathic interstitial pneumonia (45%), and idiopathic pulmonary fibrosis (28%).

It met its primary goal, that of greater exercise capacity in treated patients, the company announced earlier this year.

Data presented at CHEST showed that over the 16-week study, patients given Tyvaso had significantly fewer exacerbations (26.4%), or flares in which disease symptoms suddenly get worse, than those on a placebo (38.7%).

At multiple time points, participants’ lung function was assessed using forced vital capacity (FVC), a measure of the total amount of air a person can exhale with a breath, commonly used as a marker of lung function.

On average, placebo group patients experienced a decline in FVC over the course of the study, while FVC values for those on Tyvaso remained stable or increased.

Specifically, the average FVC value was 28.47 mL higher in the Tyvaso-treated group after eight weeks, and 44.40 mL higher after 16 weeks, poster data show. Similarly, in Tyvaso-treated patients, percent predicted FVC — which assesses FVC measurements based on typical values — also improved at weeks eight and 16.

Subgroup analyses found that Tyvaso-treated patients with idiopathic interstitial pneumonia or idiopathic pulmonary fibrosis experienced significant improvements in FVC, relative to disease-matched patients given placebo.

“Findings of a significant placebo-corrected difference in FVC combined with significantly fewer exacerbations in
patients receiving inhaled treprostinil compared to those receiving placebo suggest that patients on inhaled treprostinil had a favorable impact on the course of the underlying lung disease,” the researchers concluded in their poster.

Treatment with Tyvaso was well tolerated overall. Most adverse events were mild or moderate in intensity, and safety data were generally in line with previous findings for Tyvaso in other patient populations. Commonly reported side effects in the trial included cough, headache, shortness of breath, dizziness, nausea, fatigue, and diarrhea.

Of note, these findings, in combination with previous pre-clinical research indicating that Tyvaso could have anti-fibrotic effects, suggest it may be a useful treatment for ILD, even in the absence of PH.

United Therapeutics is planning a Phase 3 clinical trial, called TETON, to evaluate Tyvaso in people with chronic fibrosing ILD.

“We look forward to launching our phase 3 TETON clinical program next year; the first study … will enroll subjects with idiopathic pulmonary fibrosis,” Peterson said.