United Therapeutics Corp.

Shares in United Therapeutics climbed nearly 33% on Tuesday — adding $4.5 billion to its valuation — after the company reported that its inhaled lung disease treatment, Tyvaso (treprostinil), met the primary endpoint in pivotal study for idiopathic pulmonary fibrosis (IPF). A dry powder version of Tyvaso is approved for pulmonary arterial hypertension (PAH); the Phase III TETON-2 study evaluated a nebulised formulation of the prostacyclin mimetic dosed as three breaths four times per day. The 597-patient study met its primary efficacy endpoint of improving absolute forced vital capacity (FVC) relative to placebo. At 52 weeks, patients who received Tyvaso saw a 95.6-mL change in absolute FVC from baseline, a statistically significant increase. Analysts at Jefferies had previously estimated that Tyvaso would need to demonstrate at least a 56 mL to 80 mL FVC change to succeed in TETON-2. A more ideal result, they said, would be an absolute FVC change falling between 80 mL to 100 mL — and it looks like Tyvaso has come in at the upper end of that range.There were also no new safety signals, with Tyvaso's safety profile consistent with previous studies. If Tyvaso remained safe, and scored a high FVC change, the analysts predicted that it could become the first inhaled therapeutic to provide a favourable efficacy and safety profile versus the currently available oral drugs, suggesting substantial value addressing the growing IPF market.United's drug also met several key secondary endpoints, achieving statistically significant 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). Patients who received Tyvaso also had a significantly longer time to first clinical worsening event, relative to placebo."Existing IPF treatments offer only modest benefits, often with challenging side effects," commented Steven Nathan, chair of the TETON steering committee. "These unequivocally positive results included endpoints that were not attained in prior Phase III 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."The results, United said, support a supplemental marketing submission to the FDA to add IPF to Tyvaso's label. The drugmaker plans to meet with the US regulator by year-end to discuss the possibility of expediting the inhaled drug's review when data from its second pivotal study, TETON-1, are available in the first half of 2026. The company will share additional findings from TETON-2 at the European Respiratory Society Congress later this month.

United Therapeutics is looking to add idiopathic pulmonary fibrosis to its repertoire of lung disease benefits. United Therapeutics is making headway in unlocking a new lung disease market for its drug Tyvaso (treprostinil) with a pivotal phase 3 win in idiopathic pulmonary fibrosis (IPF).United’s Teton-2 study of Tyvaso, in its nebulized inhalation solution, hit its primary and “most” secondary endpoints, according to a Sept. 2 press release (PDF) from the company.In the study, the drug demonstrated superiority over placebo when measured by participants' change in absolute forced vial capacity (FVC) from baseline to Week 52. The absolute FVC endpoint refers to the amount of air a patient can forcefully exhale after a deep breath and is a crucial factor in diagnosing lung diseases.Several secondary endpoints also reflected statistically significant improvements, according to United. Those included the time to first clinical worsening effect and the King’s Brief Interstitial Lung Disease quality of life questionnaire, United said.Endpoints measuring the time to first acute exacerbation of IPF and overall survival didn’t reach statistical significance, the company noted, but they “trended in favor” of Tyvaso by Week 52.The “overwhelmingly positive" results have the potential to “reshape the treatment of IPF, extending new opportunities to a much broader patient population than ever before,” United’s senior vice president of product development, Peter Smith, who heads up the global Teton program, said in the company's release.The company estimates the U.S. IPF market to comprise more than 100,000 patients. United’s share price spiked by more than 33% by Tuesday afternoon, reaching a share price of $408 compared to Friday’s $304.76 at market close.Along with the Teton-2 results, United aims to make its case for a Tyvaso label expansion with an ongoing U.S. and Canada-specific Teton-1 trial that’s expected to read out in the first half of 2026. The company plans to meet with the FDA before the end of 2025 to discuss ways to potentially speed up the review process when the Teton-1 results are available, the company said. If approved, Tyvaso would make a splash in the “sizable” IPF market as the first inhaled therapy that can treat the lung disease, Jefferies analysts explained in a note to clients, describing the trial results as both clinically meaningful and competitive. As it stands, Roche’s Esbriet and Boehringer Ingelheim’s Ofev dominate the IPF space. Both are oral pills.The Jefferies team expects that Tyvaso could be used on top of current standard of care in IPF and the similar condition progressive pulmonary fibrosis.Tyvaso has been marketed since 2009 for pulmonary arterial hypertension (PAH) and generated $469.6 million in second-quarter sales across its nebulized inhalation solution and a newer dry powder inhalation. An IPF indication could bolster Tyvaso’s revenues with potentially billions of dollars on the line, Jefferies analysts forecast.  Still, William Blair analysts connected the dots between United’s win and Insmed’s path for its treprostinil palmitil inhalation powder, a treprostinil prodrug that recently scored in a phase 2 PAH study. The analysts described Tyvaso’s results as a “further validation” of inhaled treprostinil in fibrotic lung diseases and suggested that Insmed’s offering could have an “improved profile” in any indication in which nebulized Tyvaso has proven efficacy, including IPF.Mizuho analysts agreed that United’s win is a “huge net positive” for Insmed and wrote that the latter company has previously “stated its willingness” to quickly advance the candidate into phase 3 IPF studies if it posted a win in the disease. As it stands, Insmed is focused on an early 2026 trial readout in the PAH population. The company’s treprostinil prodrug works as an inactive compound that becomes active once metabolized in the body.

United Therapeutics’ stock price soared Tuesday after the company reported a Phase 3 win in a lung disease that’s had a spate of failures. Tyvaso hit the primary goal in the TETON-2 trial in idiopathic pulmonary fibrosis (IPF). Patients who took Tyvaso for one year were able to more forcefully expel air from their lungs compared to those on placebo by a highly statistically significant margin. Tyvaso also achieved most of the study’s secondary endpoints. United’s shares $UTHR were up about 35% by midday Tuesday, hitting an all-time high at one point. There has been a recent string of clinical trial failures for IPF drugs from both large and small biopharma companies. Novartis ended a Phase 2 IPF study last October, and Pliant Therapeutics discontinued a Phase 2b study for its experimental IPF drug in March. Novartis did not disclose a reason for its discontinuation, while Pliant cited “an imbalance in unadjudicated IPF-related adverse events” between the two trial arms. Meanwhile, Boehringer Ingelheim last year touted multiple Phase 3 successes for its IPF drug nerandomilast. But that drug’s efficacy underwhelmed analysts once they saw the full data and began asking questions about the drug’s potential as a combination treatment and in the real world. Then in December, PureTech reported a successful Phase 2b readout showing that deupirfenidone appeared to stack up better against nerandomilast in cross-trial comparisons. Tyvaso’s latest results garnered no such pessimism. The magnitude of the United drug’s efficacy compared to other standard-of-care treatments is “unprecedented,” Leerink analyst Roanna Ruiz wrote in a note to investors. Tyvaso was also able to provide such a benefit for patients still taking other drugs, “positioning it uniquely in the IPF treatment landscape,” Ruiz added. The FDA usually requires two Phase 3 studies to succeed for this disease, and United is running another trial called TETON-1 that should read out in the first half of next year. While TETON-2 was a global study, TETON-1 enrolled patients in the US and Canada. Tuesday’s data significantly increase the likelihood that both studies end up being positive, according to TD Cowen analyst Joseph Thome. If TETON-1 ends up as another win and Tyvaso is approved, its peak global sales in IPF could reach $2.3 billion, Thome estimates. Tyvaso has been approved for another lung condition called pulmonary arterial hypertension since 2009. But in 2022, United got a separate formulation approved using an inhalation powder, compared to the original inhaled solution. The TETON-2 trial in IPF tested the original solution formulation.