Progressive pulmonary fibrosis (PPF) describes a phenotype of non-idiopathic pulmonary fibrosis (IPF) interstitial lung diseases (ILDs) that continues to worsen despite appropriate management, leading to lung scarring, loss of lung function, and early mortality. Current antifibrotic agents slow the rate of forced vital capacity (FVC) decline but do not halt or reverse fibrosis, leaving substantial unmet needs in survival, symptom control, and quality of life. Against this backdrop, the late-stage pipeline consists of both inhaled and targeted therapies that are expected to transform PPF care, according to GlobalData, a leading intelligence and productivity platform.
Current pharmacological options are extrapolated from IPF and include Boehringer Ingelheim’s Ofev (nintedanib), and Jascayd (nerandomilast) in the US. In some circumstances, pirfenidone may also be used, although it is prescribed off-label. These antifibrotics are prescribed alongside tailored background immunomodulation for the patients’ underlying ILD.
The late-stage pipeline for PPF care includes Bristol Myers Squibb’s (BMS’s) admilparant, United Therapeutics’ Tyvaso (treprostinil), and Insmed’s treprostinil palmitil (TPIP).
Admilparant represents a next-generation approach to treating PPF that aims to reduce the accumulation of scar tissue in the lungs. It is a lysophosphatidic acid receptor 1 antagonist that reduces the activation, proliferation, and migration of fibroblasts into the lungs as well as epithelial cell apoptosis, which contributes to lung fibrosis. Phase II results demonstrated a 69% reduced rate of FVC decline compared to placebo, which is superior to the currently marketed products. However, currently no long-term survival, exacerbation, or hospitalization data has been demonstrated, and this will have to be confirmed in the upcoming Phase III trial.
Connor Daniels, Healthcare Analyst at GlobalData, comments: “If BMS can demonstrate this, as well as improved tolerability compared to the current marketed assets, then admilparant has the potential to be positioned as the best-in-class antifibrotic to treat PPF patients.”
Tyvaso is an inhaled prostacyclin agonist that is already approved for pulmonary arterial hypertension and pulmonary hypertension associated with ILD. It is now in Phase III trials to explore its potential utility in treating PPF. Preclinical and clinical evidence suggests that Tyvaso binds to both the prostaglandin E receptor 2 (EP2) and the prostaglandin D receptor 1, resulting in reduced cell proliferation and collagen secretion, as well as a reduction in lung inflammation and fibrosis.
Daniels adds: “There is currently no PPF specific data for Tyvaso, but there is an opportunity for it to be positioned as a first line treatment based on the results of the TETON-PPF trial, where Tyvaso is being trialed in combination with the current standard of care.”
Like Tyvaso, TPIP is an inhaled prostacyclin agonist, but it has a slightly different mechanism of action. Tyvaso binds directly to the receptors, whereas TPIP is a prodrug and the addition of palmitil chain allows the molecule to remain in the lung tissue longer. The molecule is then slowly hydrolyzed to release the active treprostinil, resulting in a more sustained release of the drug and lower plasma concentrations. The main benefit of this approach is that the sustained release means patients may only need to take one dose of TPIP per day, compared with the four times a day with Tyvaso.
The high peak concentrations of Tyvaso can also cause side effects, such as coughing. Insmed will therefore try to demonstrate that TPIP is more convenient and better tolerated in Phase III trials, which were announced in January 2026 but have not yet started.
Daniels concludes: “The three pipeline assets demonstrate that the PPF market may be shifting from broad antifibrotics toward more targeted therapies and assets that can be used in combination with the current standard of care, ultimately providing patients with more treatment options.”
