October 09, 2025
3 min read
Key takeaways:
- The FDA based nerandomilast’s approval on results from two trials, one of which was the FIBRONEER-IPF trial.
- This marks the first treatment approved for patients with IPF in more than a decade.
The FDA granted approval to nerandomilast, now Jascayd, for treating adults with idiopathic pulmonary fibrosis, marking the first treatment approved for this indication in more than 10 years, according to a notice from FDA.
In a press release from Jascayd’s manufacturer Boehringer Ingelheim, the company said the FDA’s decision on the phosphodiesterase 4B inhibitor was, in part, based on findings from the FIBRONEER-IPF trial and Trial 2.
The FDA granted approval to nerandomilast, now Jascayd, for treating adults with idiopathic pulmonary fibrosis.
The multicenter, randomized, double-blind, placebo-controlled FIBRONEER-IPF trial was published in The New England Journal of Medicine in May 2025 and presented at the 2025 American Thoracic Society International Conference.
In the phase 3 FIBRONEER-IPF study, adults aged 40 years or older with IPF receiving twice-daily, oral 18 mg Jascayd vs. placebo for 52 weeks had a significantly smaller degree of FVC decline (adjusted mean change, –114.7 mL vs. –183.5 mL; adjusted difference, 68.8 mL; 95% CI, 30.3-107.4; P < .001).
Similarly, a significantly smaller FVC reduction was found in those receiving 9 mg Jascayd vs. placebo (–138.6 mL vs. –183.5 mL; adjusted difference, 44.9 mL; 95% CI, 6.4-83.3; P = .02), according to the study.
Researchers continued to report less FVC decline in the subgroup of patients who used nintedanib (n = 535), with smaller FVC reductions in those receiving Jascayd vs. placebo (18 mg, –118.5 mL; 9 mg, –130.7 mL vs. –191.6 mL).
Patients in the pirfenidone subgroup (n = 380) receiving 18 mg Jascayd also had a smaller degree of FVC decline between baseline and week 52 vs. patients receiving placebo (–133.7 mL vs. –197 mL), but this was not the case when researchers compared the 9 mg Jascayd group with the placebo group (–201.8 mL vs. –197 mL).
“Jascayd dosage may be reduced for intolerability to 9 mg twice daily, expect in patients also taking pirfenidone,” the FDA wrote in its release.
Switching to Trial 2, which also included adults aged 40 years or older with IPF, Boehringer Ingelheim highlighted that the twice-daily oral 18 mg Jascayd group vs. the placebo group had a reduction in FVC decline of 91 mL at week 12.
In terms of safety, the FIBRONEER-IPF trial reported that a greater proportion of patients receiving either dose of Jascayd vs. placebo experienced diarrhea (18 mg, 41.3%; 9 mg, 31.3% vs. 16%).
The FDA and Boehringer Ingelheim further noted that COVID-19, upper respiratory tract infection, depression, decreased weight, decreased appetite, nausea, fatigue, headache, vomiting, back pain and dizziness were the most frequent side effects of Jascayd treatment.
In the FIBRONEER-IPF trial, slightly more patients receiving 18 mg and 9 mg Jascayd had to permanently discontinue treatment due to an adverse event vs. patients receiving placebo (14% and 11.7% vs. 10.7%). Additionally, researchers found that diarrhea was the adverse event commonly behind these discontinuations (6.1% and 1.8% vs. 0.5%).
Notably, both the 18 mg and 9 mg oral doses of Jascayd have also been shown to lower FVC decline vs. placebo at week 52 in patients with progressive pulmonary fibrosis in the phase 3 FIBRONEER-ILD trial.
“Jascayd is a welcome new treatment option with a well-tolerated safety profile for physicians to consider for appropriate patients,” Toby Maher, MD, PhD, professor of clinical medicine at the USC Los Angeles Keck School of Medicine and author on the FIBRONEER trials, said in the Boehringer Ingelheim release.
Perspective
The U.S. FDA approval of nerandomilast for treatment of IPF marks the first new drug approval for IPF in more than 10 years. Since 2014, the medications pirfenidone and nintedanib have been the only antifibrotic treatment options for pulmonary fibrosis of any kind, so this is a welcome development in the pulmonary fibrosis community. While they have been available for over a decade, clinical use of pirfenidone and nintedanib in IPF remains low, around a quarter of IPF patients in a 2021 study by Dempsey and colleagues using claims data, with tolerability and access challenges among the reasons for this.
The phase 3 FIBRONEER-IPF study, along with its sister study FIBRONEER-ILD in progressive non-IPF pulmonary fibrosis, was published earlier this year. Nerandomilast slowed absolute decline in FVC when compared with placebo, and the study included subjects on background pirfenidone or nintedanib or no background therapy. The most frequent adverse event was diarrhea, and this was seen more frequently with concomitant use of nintedanib, not unexpected as nintedanib use is also frequently complicated by diarrhea. Due to a drug interaction, only the higher 18 mg dose of nerandomilast should be used with concomitant pirfenidone.
The unmet needs in IPF remain significant, and the approval of nerandomilast begins to close the gap by adding a third antifibrotic option to the arsenal. Nerandomilast may be used as monotherapy or as an add-on to nintedanib or pirfenidone, but it remains to be seen how pulmonologists will utilize these options in the clinic and how payers shape the framework with their own priorities and requirements.
Ultimately, a biomarker that predicts treatment response to the various options would be ideal. But in the meantime, I will plan to continue my current practice of shared decision-making based on patient values and preferences, although I will expect these conversations to take a little longer with a third option on the menu. Clinicians prescribing nerandomilast should be prepared to discuss the expected benefits and possible side effects and plan for close follow-up, especially for patients on combination therapy, in case tolerability is an issue.
Moving forward, real world data will be important in understanding trends in utilization, management and clinical response outside a tightly controlled trial setting. Comparative effectiveness studies would be helpful in charting the treatment paradigm and defining treatment success and failure beyond tolerability.
References:
Dempsey TM, et al. Ann Am Thorac Soc. 2021;doi:10.1513/AnnalsATS.202007-901OC.
Richeldi L, et al. N Engl J Med. 2025;doi:10.1056/nejmoa2414108.
Amy Hajari Case, MD, FCCP
Disclosures: Case reports being a site principal investigator on both of Boehringer Ingelheim’s FIBRONEER (IPF and ILD) protocols.
