Nerandomilast slows lung function decline in IPF, PPF: Clinical trials
Developer seeking approval in US, EU, China, with other countries to follow
Nerandomilast, Boehringer Ingelheim’s investigational oral therapy, significantly slowed lung function decline in people with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) after a year of treatment, according to final data from two Phase 3 clinical trials.
FIBRONEER-IPF (NCT05321069) enrolled 1,177 IPF patients, while FIBRONEER-ILD (NCT05321082) enrolled 1,176 adults with progressive forms of pulmonary fibrosis other than IPF.
Because the studies met their primary goal, the company has submitted applications seeking the approval of nerandomilast to treat both IPF and PPF in the U.S., the European Union, and China, with other countries to follow.
“Having two phase III trials meet the primary endpoint is a major breakthrough for the scientific community, highlighting nerandomilast’s potential to have a meaningful impact on patients’ unmet needs,” Toby Maher, MD, PhD, trial investigator and professor at the Keck School of Medicine of the University of Southern California in Los Angeles, said in a company press release.
Results from the trials were published in The New England Journal of Medicine in two separate studies: “Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis” and “Nerandomilast in Patients with Progressive Pulmonary Fibrosis.” Data were also presented as a late-breaking abstract at the American Thoracic Society 2025 International Conference, held this month in San Francisco.
Lung function declined less in IPF patients receiving nerandomilast
Pulmonary fibrosis (PF) is marked by scarring, or fibrosis, in the lungs, which causes them to stiffen and harden. This results in symptoms such as shortness of breath, a dry and hacking cough, and fatigue. IPF is a type of PF and has an unknown cause, while PPF encompasses lung diseases other than IPF in which symptoms and signs of fibrosis progressively worsen.
“Idiopathic pulmonary fibrosis and progressive pulmonary fibrosis are devastating conditions, with one in two people dying within five years of IPF diagnosis,” said Shashank Deshpande, head of human pharma and member of the board of managing directors at Boehringer. “Despite this stark reality, ongoing research may provide new possibilities for patients, as there remains a need for additional therapies.”
Nerandomilast (BI 1015550) is designed to block the activity of phosphodiesterase 4B (PDE4B), a pro-inflammatory enzyme involved in fibrosis. It’s expected to reduce inflammation and scarring in PF, thereby slowing or stopping lung function decline.
FIBRONEER-IPF participants were randomly assigned to receive one of two nerandomilast doses (9 mg or 18 mg) or a placebo, twice daily, for one year. At enrollment, most participants (77.7%) were also receiving the antifibrotic therapy Ofev (nintedanib) or Esbriet (pirfenidone).
The study’s primary goal was to assess changes in lung function, as measured by forced vital capacity, the maximum amount of air forcibly exhaled after a deep breath.
Idiopathic pulmonary fibrosis and progressive pulmonary fibrosis are devastating conditions, with one in two people dying within five years of IPF diagnosis. Despite this stark reality, ongoing research may provide new possibilities for patients, as there remains a need for additional therapies.
After one year, the lung function of IPF patients who received the placebo declined more, by a mean of 183.5 mL, than that of patients who were treated with the lower dose (mean decline of 138.6 mL) or higher dose (mean decline of 114.7 mL) of nerandomilast. Differences between both doses and the placebo were statistically significant, meeting the trial’s primary goal.
Similar results were observed in the subset of IPF patients who were not on antifibrotic therapy.
A composite secondary goal combining the time to the first acute pulmonary exacerbation, the first hospitalization for respiratory cause, or death was not met.
The most frequent adverse event was diarrhea, which was also the most common reason for participants to drop out of the trial. Diarrhea most commonly occurred in patients treated with the lower (31.1%) and higher dose of nerandomilast (41.3%) than in those given the placebo (16%). Other adverse events were balanced across all three treatment groups, including vasculitis (blood vessel inflammation), depression, suicidality, drug-induced liver injury, or fatalities.
Similar results seen in ILD, IPF clinical trials
In FIBRONEER-ILD, patients were randomly assigned to receive the same doses of nerandomilast given in the other trial or a placebo, with 43.5% receiving Ofev at enrollment. Two patients took Esbriet rather than Ofev, but were analyzed as part of the same group.
After one year, the lung function of PPF patients who received a placebo declined more, by a mean of 165.8 mL, compared with that of patients given the 9 mg (mean decline of 84.6 mL) and the 18 mg dose of nerandomilast (mean decline of 98.6 mL). Again, there was a statistically significant difference between the treatment and placebo groups.
The same trend was seen in PPF patients who were not on antifibrotic therapy.
Like in FIBRONEER-IPF, the composite secondary measure in this trial was not met. Still, there were fewer deaths in the two nerandomilast dose groups than in the placebo group.
The safety and tolerability profile of nerandomilast in this trial was largely consistent with FIBRONEER-IPF data, with diarrhea being more frequently reported in the 9 mg (29.5%) and 18 mg (36.6%) groups than in the placebo group (24.7%). The occurrence of all other adverse events was similar across the treatment groups.
“The latest efficacy, safety and tolerability data on nerandomilast points to its potential in addressing the needs of those impacted by IPF and PPF,” Deshpande said.
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