Tyvaso found to preserve lung function in those with IPF in large global trial
Inhaled therapy may be 'a true advancement' in care, per developer
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Treatment with Tyvaso (treprostinil) outperformed a placebo at preserving lung function and preventing clinical worsening — meaning, it led to gains beyond temporary symptom changes — among people with idiopathic pulmonary fibrosis (IPF) in the now-completed global TETON-2 clinical trial.
United Therapeutics, Tyvaso’s developer and the study’s sponsor, announced a few months ago that the Phase 3 trial testing the inhaled therapy had met its main goal. Now, the findings have undergone peer review, a process in which independent scientists go over the data. Full results from the TETON-2 trial were detailed in a paper titled “Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis,” published in The New England Journal of Medicine.
Data from the pivotal study showed “a statistically significant preservation of lung function across all [patient] subgroups,” as well as “fewer clinical worsening events” for treated participants over one year relative to those on the placebo, according to a company press release. United also noted that “the trial population reflected the characteristics of a general population of IPF patients,” with three-quarters of the participants already on a background treatment.
“The publication of TETON-2 in The New England Journal of Medicine marks a pivotal moment for the IPF community. For too long, patients have had limited options to treat this devastating disease,” said Martine Rothblatt, PhD, United’s chairperson and CEO.
According to Rothblatt, “nebulized Tyvaso has the potential to be the first and only inhaled anti-fibrotic treatment for IPF — a true advancement for patients and physicians alike.”
An inhalation therapy given via a portable, hand-held device, Tyvaso works by mimicking a naturally-occurring signaling molecule called prostacyclin. The therapy is approved to treat some forms of pulmonary hypertension, a condition in which there is abnormally high pressure in the vessels that carry blood from the heart through the lungs. By mimicking prostacyclin, Tyvaso can prompt blood vessels to relax and widen.
TETON 2 trial involved nearly 600 people worldwide with IPF
United notes the therapy has also shown antifibrotic effects, supporting its potential use in IPF, which is marked by fibrosis, or scarring, in the lungs.
The full results of this study … show that nebulized Tyvaso has the potential to transform IPF treatment and could serve as a first-line, inhaled therapy.
“Tyvaso’s unique antifibrotic mechanism, combined with notable clinical trial observations of improved lung function, led us to hypothesize that it could potentially serve as an effective treatment for patients with fibrotic lung disease,” said Peter Smith, senior vice president of product development at United, who also serves as the lead for the global TETON program.
“The full results of this study support our theory and show that nebulized Tyvaso has the potential to transform IPF treatment and could serve as a first-line, inhaled therapy,” Smith said.
The TETON 2 clinical trial (NCT05255991) enrolled nearly 600 adults with IPF in multiple countries. Participants were randomly assigned to take Tyvaso or a placebo via a nebulizer, four times daily. The study’s main goal was to assess the impact of treatment on forced vital capacity (FVC), a common measure of lung function that measures how much air someone can blow out in one sharp breath.
The results showed that, in patients given the placebo, the average FVC worsened by 136.4 mL after one year. By contrast, for patients given Tyvaso, the rate of FVC decline was significantly slower: After a year, the average FVC worsened by 49.9 mL.
Similar differences were seen in patients who were not taking other IPF therapies and in patients who were also taking the approved treatments Ofev (nintedanib) and/or pirfenidone (sold as Esbriet, with generics available).
Trial data show improvement in patients’ quality of life
A key secondary goal of the study was to compare rates of so-called clinical worsening, a composite event that encompasses death from any cause, as well as hospitalization due to lung problems or FVC worsening by at least 10% relative to norms.
These results showed rates of clinical worsening were significantly lower in patients given Tyvaso than in the placebo group.
“In this trial, [Tyvaso] was associated with a smaller decline in FVC and fewer clinical-worsening events than placebo over a period of 52 weeks in patients with IPF,” the researchers wrote.
Other secondary goals of the study included comparing the impact of treatment on time to first IPF exacerbation — disease flares where lung function suddenly worsens. No significant difference was seen in patients given Tyvaso or the placebo using this metric, the results showed.
Tyvaso was shown, however, to improve diffusing capacity, another measure of lung function, and to increase patient-reported measures of life quality, according to Steven D. Nathan, MD, who serves as chair of the TETON steering committee at Inova Fairfax Hospital in Virginia.
“TETON-2 not only met its primary endpoint of change in FVC but also attained statistical significance for time to clinical worsening,” said Nathan, who is also the study’s lead author.
“We also saw improved change in the diffusing capacity and, importantly, in patients’ quality of life. This achievement in patients with mild to moderate IPF over 52 weeks speaks to both the efficacy of the medication and the advantage of direct deposition through the inhaled route,” Nathan said.
Safety data in line with Tyvaso’s known profile
Safety data from TETON-2 were overall in line with Tyvaso’s known safety profile.
The most common safety issues reported in the study were cough, headache, and diarrhea, all of which are well-established as potential side effects of Tyvaso. These side effects were usually not serious. Side effects were the primary reason for study discontinuation among participants taking Tyvaso or the placebo, per the researchers.
To further test Tyvaso in IPF patients, United also launched an identical Phase 3 trial called TETON-1 (NCT04708782). That study enrolled participants in the U.S., Canada, and Chile. The company said the trial is ongoing with results expected soon.
United said it plans to use data from both TETON programs to file for regulatory approvals of Tyvaso as a treatment for IPF later this year.
Rothblatt said: “At United Therapeutics, our mission has always been to develop innovative therapies for patients with life-threatening pulmonary conditions.”
