Emerging Phase III evidence for inhaled treprostinil in progressive pulmonary fibrosis (PPF) is reinforcing industry expectations that combination therapy will shape the next phase of fibrotic lung disease treatment. TETON-PPF trial data presented at the 2026 American Thoracic Society (ATS) International Conference highlights the potential for inhaled therapies to complement existing antifibrotics, while intensifying competitive dynamics in a market with significant unmet need and growing late-stage pipeline activity, according to GlobalData, a leading intelligence and productivity platform
At ATS 2026, United Therapeutics presented Phase III TETON-PPF trial design and enrolment details for Tyvaso (inhaled treprostinil) in PPF. The 52-week study is evaluating the efficacy, safety, and tolerability of four-times-daily inhaled Tyvaso in 698 adults with PPF. Patients were randomized to receive either inhaled Tyvaso or placebo, with eligibility requiring >10% fibrotic extent on high-resolution CT imaging and FVC ≥45% predicted.
As an inhaled prostacyclin agonist with antifibrotic and anti-inflammatory properties, Tyvaso could expand combination treatment options in PPF, although increasing late-stage pipeline competition may challenge future market positioning.
Connor Daniels, Healthcare Analyst at GlobalData, comments: “Crucially, over half of the participants enrolled in the study so far are receiving background antifibrotic therapy, 44.9% are receiving nintedanib and 13% are receiving pirfenidone. This means that the TETON-PPF dataset will directly inform the combination therapy question that KOLs identified as one of the most important unresolved clinical issues in PPF management.”
The TETON-1 (NCT04708782) and TETON-2 (NCT05255991) studies investigating Tyvaso in patients with IPF were impressive, with both studies meeting the primary endpoint of change from baseline in absolute FVC at week 52 as well as several secondary endpoints, including time to first clinical worsening.
Daniels adds: “PPF remains an indication with untapped potential for drug developers, with only two marketed assets and one off-label treatment. This creates an opportunity for Tyvaso as it has a MoA that can sit adjacent to, rather than directly competing with, existing antifibrotics.”
The key opinion leaders (KOLs) previously interviewed by GlobalData have noted that they see combination therapy as the future for PPF treatment and they expect Tyvaso to play an important role in this. However, KOLs also noted that the four times daily dosing and the high cost of the therapy has led to reduced compliance in other indications.
Additionally, Tyvaso may experience increased competition from Insmed’s next-generation prodrug treprostinil palmitil, which is expected to enter Phase III clinical trials in H2 2026 and has been designed to have improved pharmacokinetics and more convenient dosing.
If Insmed can demonstrate comparable efficacy with a reduced dosing burden, they could quickly become the preferred inhaled treatment for PPF. United Therapeutics will therefore have to quickly establish an early clinical and commercial foothold and leverage physician familiarity with Tyvaso from other indications and real-world evidence to stay ahead in the PPF market.
Daniels concludes: “A positive result would further validate inhaled prostacyclin as meaningful addition to the PPF treatment paradigm and help create a commercially attractive combination therapy alongside nintedanib and pirfenidone. However, United Therapeutics faces a narrow window to establish clinical and commercial dominance before the potential launch of the next generation pipeline asset treprostinil palmitil, which has been designed to address the dosing burden of Tyvaso.”
