A TETON-2 post hoc analysis at CHEST 2026 found 126 progression events with inhaled treprostinil vs 161 with placebo across 52 weeks.
A post hoc analysis of the phase 3 TETON-2 trial presented at the
In the primary TETON-2 analysis, inhaled treprostinil produced a smaller decline in forced vital capacity (FVC) and a lower hazard of clinical worsening compared with placebo across 52 weeks (hazard ratio [HR], 0.71; log-rank P =.02).¹,² Clinical worsening was a composite of death, respiratory hospitalization, or a ≥ 10% relative decline in percent predicted FVC, measured as time to the first event. Because the endpoint stops at the first event, a less severe outcome such as an FVC decline can close out a patient’s contribution before later hospitalizations, exacerbations, or deaths are counted.
“Once someone has one of those events, it kind of draws a curtain on what happens subsequently,” said investigator Steven D. Nathan, MD, director of the Advanced Lung Disease Program and medical director of the lung transplant program at Inova Fairfax Hospital, in an interview with HCPLive. “If you look at just one progression event, it’s, for want of a better analogy, running a half marathon. But what happens if you run the full marathon?”
Nathan and colleagues analyzed patients in the TETON-IPF program for every disease progression event occurring during the 52-week study period, not only the first.¹ Qualifying events included a ≥10% relative decline in percent predicted FVC, adjudicated respiratory-related hospitalization, adjudicated acute exacerbation of IPF, concurrent exacerbation plus respiratory hospitalization, and death.
TETON-2, a randomized, double-blind, placebo-controlled phase 3 trial, enrolled 597 patients, and results from the 598-patient TETON-1 study were pending at the time of abstract submission.¹ Baseline characteristics were balanced between the inhaled treprostinil and placebo groups.
In TETON-2, 126 total events occurred in 82 patients receiving inhaled treprostinil, compared with 161 events in 115 patients receiving placebo (P =.003).¹ A numerically greater proportion of patients in the placebo group experienced > 1 progression event (39% [n = 36] vs 28% [n = 26]; P <.166). According to Nathan, patients with 1 event tended to go on to accumulate additional events, a pattern more pronounced in the placebo group.
The investigators displayed recurrent events in a waterfall plot, which accounts for both first and subsequent occurrences of progression within each patient.¹ Nathan described the color-coded plot as an outcomes heat map, showing both the total burden of events in each arm and the specific type of each event.
The most frequent events in the inhaled treprostinil and placebo groups were ≥ 10% relative decline in percent predicted FVC (54 vs 86 events), concurrent IPF exacerbation with respiratory hospitalization (6 vs 18 events), and death (17 vs 23 events).¹ Adjudicated respiratory hospitalizations were numerically more frequent with inhaled treprostinil (45 vs 34 events). The investigators attributed the difference in total events primarily to FVC decline and concurrent exacerbation with hospitalization.
Nathan also pointed to mortality following a first progression event, which he said was approximately halved with inhaled treprostinil, at roughly 22 deaths in the treatment arm vs 44 with placebo. The abstract did not report safety outcomes.
“Patients and providers need to persist with the therapy because there are going to be benefits beyond the initial progression events,” said Nathan. The investigators concluded the results support continuing inhaled treprostinil after any clinical worsening event.¹
The FDA has accepted a supplemental New Drug Application (sNDA) for nebulized inhaled treprostinil in IPF based on TETON-1 and TETON-2, with a decision anticipated in late April 2027, according to United Therapeutics.³ TETON-1 results, presented at ATS 2026, showed a 33% reduction in the risk of clinical worsening with inhaled treprostinil (HR, 0.67).⁴ Inhaled treprostinil remains investigational for IPF.
Editor’s note: Reported disclosures for Nathan include Boehringer Ingelheim Pharmaceuticals, United Therapeutics Corporation, and more.
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