Tyvaso Improved Lung Function in IPF Patients With PH

Four months of treatment with Tyvaso (inhaled treprostinil) significantly improved lung function in adults with pulmonary hypertension associated with interstitial lung disease (PH-ILD), according to a post-hoc analysis of data from the Phase 2/3 INCREASE clinical trial.

PH-ILD comprises a group of conditions characterized by significant lung scarring (fibrosis), including idiopathic pulmonary fibrosis (IPF).

Notably, these lung improvements were more pronounced in the subgroup of IPF patients, supporting Tyvaso’s evaluation as a potential treatment for IPF — the goal of the recently launched Phase 3 TETON trial (NCT04708782). The trial is currently recruiting adults with IPF at seven of its predefined 21 sites across the U.S.

“Patients with IPF have generally used two therapies that modestly slow the progression of their disease but come with challenging side effects that can make treatment difficult,” Gil Golden, MD, PhD, United Therapeutics’ chief medical officer, said in a press release.

“This analysis is exciting because rather than slowing down the rate of FVC [forced vital capacity] deterioration, Tyvaso actually improved FVC in the relatively short 16-week duration of the INCREASE study,” Golden said.

FVC is a standard lung function parameter that measures how much air a person is able to exhale after a deep breath.

“If the TETON study supports eventual approval of Tyvaso in patients with IPF, we look forward to providing a new treatment option for these patients with few current treatment options for this life-threatening medical condition,” Golden said.

These findings were shared in the study, “Inhaled treprostinil and forced vital capacity in patients with interstitial lung disease and associated pulmonary hypertension: a post-hoc analysis of the INCREASE study,” published in The Lancet Respiratory Medicine.

Tyvaso, delivered directly to the lungs through a portable handheld device, is a liquid-based inhaled formulation of treprostinil, a vasodilator agent that is able to lower blood pressure by relaxing and widening blood vessels in the lungs.

Tyvaso is approved in the U.S. to treat pulmonary arterial hypertension (PAH) and to improve exercise ability in people with PH-ILD. PAH is a condition in which the narrowing of the arteries that connect the heart to the lungs result in high blood pressure.

Previous preclinical studies suggested that Tyvaso also has anti-fibrotic properties.

Last year, the therapy received orphan drug designation in the U.S. for treating IPF, which is meant to accelerate its development and regulatory review.

The Phase 2/3 INCREASE study (NCT02630316) evaluated the safety and effectiveness of 16 weeks (about four months) of treatment with Tyvaso against a placebo in 326 adults with PH-ILD. Participants inhaled up to 12 breaths of either Tyvaso or a placebo, four times daily.

Top-line results showed that Tyvaso significantly increased patients’ exercise capacity — as assessed with the six-minute walking distance test — after four months of treatment, compared with a placebo, meeting the trial’s main goal.

INCREASE also met its secondary goals, with Tyvaso-treated patients showing significant reductions in NT-proBNP — a marker of heart strain — and a 39% lower risk of clinical worsening relative to those given a placebo.

Notably, these benefits, along with significantly fewer disease flares (sudden symptom worsening) and improvements in lung function, were observed across key patient subgroups, such as those based on the underlying lung fibrotic disease.

Tyvaso was generally well-tolerated, and its safety profile was consistent with that reported in previous trials. The most frequently reported adverse side effects included cough, headache, shortness of breath, dizziness, nausea, fatigue, and diarrhea.

Newly published data concerned a post-hoc analysis of INCREASE — an examination conducted after the completion of the trial. It sought to further investigate the effects of Tysavo in patients’ lung function, as assessed with FVC.

Results showed that compared with placebo, Tysavo was associated with improvements in lung function, representing a 1.8% significant increase in FVC after both two and four months of treatment.

Subgroup analysis revealed that adults with PH associated with IPF benefited the most from Tysavo in terms of lung function. When treated with Tysavo, this subgroup showed the greatest FVC differences relative to those on a placebo at two and four months of treatment, reaching statistical significance at four months.

Leigh Peterson, PhD, senior vice president of United’s product development, said that FVC was measured in the INCREASE study “as a safety endpoint to make sure treatment with Tyvaso was not exacerbating patients’ underlying lung diseases.

“What we found was quite to the contrary, as we saw improvement in lung function among several subgroups including those with PH associated with IPF,” Peterson added.

“These data, collected in patients presenting with IPF plus pulmonary hypertension, warrant the further investigation of [Tyvaso]’s effects in patients diagnosed with IPF alone, before their disease progresses and they develop pulmonary hypertension,” said Steven Nathan, MD, an INCREASE investigator and steering committee member.

Nathan is the director of the advanced lung disease program and the lung transplant program at Inova Fairfax Hospital in Falls Church, Virginia, and a professor of medicine at Virginia Commonwealth University-Inova Campus.

“We are looking to expand on these results in the TETON study, in hopes of demonstrating a label-enabling FVC improvement in patients with IPF,” Peterson said.

The placebo-controlled Phase 3 TETON trial, which enrolled its first patient in June, is assessing Tysavo’s safety and effectiveness in up to 396 adults, ages 40 and older, with IPF.

Participants will be assigned randomly to receive either Tysavo or a placebo for one year, after which they will have the option to receive the therapy for two years in an open-label extension study (NCT04905693).

TETON’s main goal is to evaluate changes in patients’ lung function, as measured by FVC, while secondary goals include time to clinical worsening, time to first IPF flare, and overall survival.

United also is seeking approval in the U.S. of Tysavo DPI, an experimental dry powder inhaled formulation of treprostinil, for PAH and PH-ILD. The regulatory application is currently under priority review, which may shorten the review process to eight months from the standard 12 months.