Deupirfenidone Advances to Phase 3 Trial for Idiopathic Pulmonary Fibrosis

Deupirfenidone, a potential new treatment for idiopathic pulmonary fibrosis, is set to be tested in a phase 3 trial this year after a successful phase 2b trial and meeting with the FDA. The FDA and the European Commission granted orphan drug designation to support the late-stage development of the drug deupirfenidone, an antifibrotic and deuterated form of pirfenidone.

If this trial yields positive results, deupirfenidone would be one step closer to becoming the fourth therapy for IPF to receive FDA approval. There are currently 3 FDA-approved therapies to treat IPF: nerandomilast (JASCAYD; Boehringer Ingelheim), nintedanib (OFEV; Boehringer Ingelheim), and pirfenidone (Esbriet; Genentech). Nerandomilast, an oral phosphodiesterase-4B inhibitor, was approved in 2025 and is the first new IPF therapy approved in more than 10 years.

In the phase 2b ELEVATE IPF trial, patients with IPF had less FVC decline between baseline and 26 weeks with receipt of three daily doses of 825 mg deupirfenidone vs. placebo. Relative to the lung function decline with placebo, patients receiving 825 mg deupirfenidone also experienced a 50% greater treatment effect than those receiving the FDA-approved dose of 801 mg pirfenidone (80.9% vs. 54.1%).

Deupirfenidone is a next generation antifibrotic and a deuterated form of pirfenidone, one of the three FDA-approved therapies for IPF. Deuteration involves replacing select hydrogen atoms with deuterium, a heavier and more stable isotope, with the goal of slowing the drug's metabolic breakdown. This approach may offer the ability to achieve higher drug exposure that could significantly improve efficacy outcomes without sacrificing tolerability.

At a dose of 825 mg three times daily, deupirfenidone demonstrated an approximately 50% greater treatment effect than pirfenidone 801 mg three times daily, based on reductions in lung function decline relative to placebo (80.9% vs. 54.1%). This enhanced effect was associated with approximately 50% higher drug exposure compared with pirfenidone at similar doses. Importantly, the increased exposure achieved with deupirfenidone was not accompanied by a worsening of tolerability.

In the phase 3 SURPASS-IPF trial, researchers will evaluate deupirfenidone vs. pirfenidone. For more than a decade after the approval of the first antifibrotics, there was essentially no successful therapeutic innovation in IPF. The two cornerstone antifibrotic therapies, pirfenidone and nintedanib, were approved over 10 years ago, and despite numerous late-stage development efforts since then, most programs failed to demonstrate meaningful benefit.

Historical data suggest that only one out of four people living with IPF in the United States has ever started treatment with an approved antifibrotic. While pirfenidone and nintedanib represented important advances at the time of approval, their real-world impact has been limited by a challenging balance between efficacy and tolerability. Both therapies offer only modest slowing of lung function decline, and their side effects frequently limit dose optimization, treatment initiation and long-term adherence.

Although there is no absolute cure for IPF, many of the approved therapies, alone and in combination, have been shown to slow the rate of disease progression. All 3 drugs have been shown to slow the rate of forced vital capacity decline in patients with IPF. An overwhelming number of patients with IPF experience adverse events that frequently impact their quality of life, despite treatment with antifibrotics. Although the majority of 106 patients surveyed said that the treatment "gave them hope" and helped slow the progression of their disease, approximately 90% said they experienced at least 1 adverse event as a result of treatment.

With at least 20 therapies in Phase II testing for idiopathic pulmonary fibrosis — most with first-in-class potential — the next two years are poised to deliver proof-of-concept readouts that help identify the signaling pathways most central to fibrosis progression and guide development strategy.