Full Press Release Details
United Therapeutics Corporation Announces
TETON-2 Pivotal Study of Tyvaso Meets Primary Endpoint for the Treatment of Idiopathic Pulmonary Fibrosis
Positive results were observed
across all subgroups
Study meets several key secondary
endpoints with statistical significance
SILVER SPRING, Md. and RESEARCH
TRIANGLE PARK, N.C., September 2, 2025: United Therapeutics Corporation (Nasdaq: UTHR), a public benefit corporation, today announced
that its TETON-2 study evaluating the use of nebulized Tyvaso (treprostinil) Inhalation Solution for the treatment of idiopathic
pulmonary fibrosis (IPF) met its primary efficacy endpoint of demonstrating improvement in absolute forced vital capacity (FVC)
relative to placebo.
Tyvaso demonstrated superiority
over placebo for the change in absolute FVC by 95.6 mL (Hodges-Lehmann estimate, p <0.0001) from baseline to week 52 in patients with
IPF. Benefits of Tyvaso were observed across all subgroups, such as use of background therapy (nintedanib, pirfenidone, or no background
therapy), smoking status, and supplemental oxygen use.
Statistically significant improvements
relative to placebo were also observed in most secondary endpoints, including time to first clinical worsening event, as well as changes
from baseline to week 52 in percent predicted FVC, King's Brief Interstitial Lung Disease quality of life questionnaire (K-BILD),
and diffusion capacity of lungs for carbon monoxide (DLCO). While not statistically significant, both time to first acute exacerbation
of IPF and overall survival at week 52 trended in favor of Tyvaso. Treatment with Tyvaso was well-tolerated, and the safety profile was
consistent with previous Tyvaso studies and known prostacyclin-related adverse events. No new safety signal was seen.
"It is a profound honor
to witness the power of scientific innovation realized for patients in need," said Martine Rothblatt, Ph.D., Chairperson
and Chief Executive Officer of United Therapeutics. "TETON-2's successful outcome affirms the anti-fibrotic
power of Tyvaso. We have unlocked new hope for patients with IPF and their families."
"These overwhelmingly positive
data send a clear signal of the potential benefits of Tyvaso for patients with IPF," said Peter Smith, Pharm. D., Senior
Vice President, Product Development at United Therapeutics and the lead for the global TETON program. "We are deeply grateful
to every patient who participated in this important study and the investigators whose dedication made this milestone possible. These results
have the potential to reshape the treatment of IPF, extending new opportunities to a much broader patient population than ever before."
"As clinicians, we witness
firsthand the devastating impact of IPF, with limited therapies to offer these vulnerable patients under our care," said Steven
D. Nathan, M.D., Schar Chair, Advanced Lung Disease and Lung Transplant Program at Inova Fairfax Hospital and Chair of the TETON
Steering Committee. "Existing IPF treatments offer only modest benefits, often with challenging side effects. These results
represent a major step forward, giving us hope for improving outcomes in patients who desperately need better options. These unequivocally
positive results included endpoints that were not attained in prior phase 3 IPF clinical trials - including, importantly, a difference
in quality of life. It is also notable that most patients were already on standard of care anti-fibrotic therapy, which makes these results
even more impressive. We are especially excited for our patients, as these results offer a renewed sense of hope."
United Therapeutics intends to use the data from both the TETON-2
study and the ongoing TETON-1 study of nebulized Tyvaso (NCT04708782) to support a supplemental New Drug Application
to the FDA to add IPF to the labeled indications for nebulized Tyvaso. United Therapeutics plans to meet with the FDA before the end
of the year to discuss ways to potentially expedite the regulatory review process when TETON-1 results are available. Data
readout from TETON-1 is expected in the first half of 2026. Both the FDA and the European Medicines Agency have granted orphan
designation for treprostinil to treat IPF.
Additional TETON-2 study results
will be presented at the European Respiratory Society Congress in Amsterdam on September 28, 2025.
TETON-2 study (NCT05255991) was a 597-patient, multicenter, randomized, double-blind,
placebo-controlled phase 3 registration study evaluating the safety and efficacy of nebulized Tyvaso in subjects with IPF over a 52-week
period at sites in Argentina, Australia, Belgium, Chile, Denmark, France, Germany, Israel, Italy, Mexico, the Netherlands, New Zealand,
Peru, South Korea, Spain, and Taiwan. The study achieved full enrollment in July 2024.
Subjects were randomly assigned
1:1 to receive nebulized Tyvaso or placebo, stratified by IPF background therapy use. All subjects initiated nebulized Tyvaso or placebo
at a dose of three breaths administered four times daily (QID) and titrated to a target dosing regimen of 12 breaths QID. Study
drug doses were titrated up as tolerated, until the target dose or maximum clinically tolerated dose was achieved.
The primary endpoint of the study
was the change in absolute FVC from baseline to week 52. Secondary endpoints included: (1) time to clinical worsening; (2) time to first
acute exacerbation of IPF; (3) overall survival at week 52; (4) change in percent predicted FVC from baseline to week 52; (5) change in
the K-BILD questionnaire from baseline to week 52; and (6) change in DLCO from baseline to week 52.
Safety assessments included the
development of adverse events, serious adverse events, vital signs, clinical laboratory parameters, and electrocardiogram parameters.
Eligible subjects completing the TETON-2
study could enroll in the TETON-OLE study (NCT04905693), an ongoing open-label extension study to evaluate the long-term
safety and tolerability of nebulized Tyvaso in subjects with fibrotic lung disease.
pulmonary fibrosis, or IPF, is a scarring disease of the lungs of an unknown (idiopathic) cause
and is the most common of the idiopathic interstitial pneumonias. IPF is characterized by the progressive loss of the ability of the
lungs to transfer oxygen into the blood, ultimately resulting in respiratory failure and death. While the precise causes of IPF remain
unknown, IPF rarely presents before age 50 and can be associated with cigarette smoking and certain genetic dispositions. In addition,
some evidence suggests that gastroesophageal reflux (acid reflux, or heartburn), certain viral infections, air pollution, and workplace
exposures may be risk factors for IPF. According to recent research, IPF is estimated to affect between 0.33 and 4.51 people per
10,000 persons worldwide. Further, United Therapeutics estimates there are over 100,000 IPF patients in the United States.
About Tyvaso (treprostinil)
TYVASO (treprostinil) Inhalation Solution is a prostacyclin mimetic
indicated for the treatment of:
The effects diminish over the minimum recommended dosing
interval of 4 hours; treatment timing can be adjusted for planned activities.
While there are long-term data on use of treprostinil by
other routes of administration, nearly all clinical experience with inhaled treprostinil has been on a background of an endothelin receptor
antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor. The controlled clinical experience with TYVASO was limited to 12
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
TYVASO is a pulmonary and systemic vasodilator. In patients with low
systemic arterial pressure, TYVASO may produce symptomatic hypotension.
TYVASO inhibits platelet aggregation and increases the risk of bleeding.
Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (e.g.,
gemfibrozil) may increase exposure (both Cmax and AUC) to treprostinil. Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin)
may decrease exposure to treprostinil. Increased exposure is likely to increase adverse events associated with treprostinil administration,
whereas decreased exposure is likely to reduce clinical effectiveness.
Like other inhaled prostaglandins, TYVASO may cause acute bronchospasm.
Patients with asthma or chronic obstructive pulmonary disease (COPD), or other bronchial hyperreactivity, are at increased risk for bronchospasm.
Ensure that such patients are treated optimally for reactive airway disease prior to and during treatment with TYVASO.
DRUG INTERACTIONS/SPECIFIC POPULATIONS
The concomitant use of TYVASO with diuretics, antihypertensives, or
other vasodilators may increase the risk of symptomatic hypotension.
Human pharmacokinetic studies with an oral formulation of treprostinil
(treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor, gemfibrozil, increases exposure
(both Cmax and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer, rifampin, decreases exposure to treprostinil. It
is unclear if the safety and efficacy of treprostinil by the inhalation route are altered by inhibitors or inducers of CYP2C8.
Limited case reports of treprostinil use in pregnant women are insufficient
to inform a drug-associated risk of adverse developmental outcomes. However, pulmonary arterial hypertension is associated with an increased
risk of maternal and fetal mortality. There are no data on the presence of treprostinil in human milk, the effects on the breastfed infant,