The US Food and Drug Administration has approved JASCAYD (nerandomilast) tablets for treating progressive pulmonary fibrosis in adults, marking the drug's second indication following its recent approval for idiopathic pulmonary fibrosis. The approval positions nerandomilast as the first and only preferential phosphodiesterase 4B inhibitor with immunomodulatory and antifibrotic effects available for progressive pulmonary fibrosis treatment.
The FDA's decision was based on results from FIBRONEER-ILD, described as the largest clinical trial program in progressive pulmonary fibrosis (PPF) to date. In the phase 3 study, patients receiving JASCAYD at 18 mg demonstrated an adjusted mean decline in forced vital capacity of -86 mL from baseline at week 52, compared with -152 mL in the placebo group, yielding a treatment difference of 65 mL. Patients receiving a 9-mg dose showed a -69 mL decline vs placebo, with a treatment difference of 83 mL.
"Progressive pulmonary fibrosis is linked to underlying clinical [interstital lung disease (ILD)] diagnoses including autoimmune ILDs, which can be caused by disorders like rheumatoid arthritis or systemic sclerosis – as well as hypersensitivity pneumonitis, among other conditions," said Shervin Assassi, MD, professor and director of rheumatology at McGovern Medical School, UTHealth Houston. "These underlying conditions often lead to the lungs being overlooked, yet lung scarring may lead to debilitating and irreversible impact on lung function."
JASCAYD demonstrated similar permanent discontinuation rates to placebo, with adverse events leading to treatment cessation in 10% of patients in the 18-mg group, 8% in the 9-mg group, and 10% in the placebo group. The most common adverse reactions included diarrhea, COVID-19 infection, upper respiratory tract infection, depression, weight loss, decreased appetite, nausea, fatigue, headache, vomiting, back pain, and dizziness.
The trial's key secondary composite endpoint—time to first occurrence of any component over up to 109 weeks, including acute ILD exacerbation, hospitalization for respiratory cause, or death—showed no statistically significant treatment difference between JASCAYD and placebo. However, exploratory analysis revealed that JASCAYD at 18 mg demonstrated a nominally statistically significant reduction in acute ILD exacerbations compared with placebo.
A prespecified analysis of overall survival showed hazard ratios for all-cause mortality at up to 114 weeks of 0.51 for both the 18 mg and 9 mg doses compared with placebo, though these results were not prespecified for multiplicity control.
Diarrhea occurred more frequently in patients using concomitant nintedanib. Among patients taking background nintedanib, diarrhea was reported in 49% of those receiving JASCAYD at 18 mg twice daily, 50% receiving 9 mg twice daily, and 37% receiving placebo. Without concomitant nintedanib, diarrhea occurred in 27%, 16%, and 16% of patients, respectively.
Diarrhea was the most common adverse reaction associated with treatment discontinuation and occurred most frequently in patients treated with JASCAYD 18 mg (4%) or JASCAYD 9 mg (3%) with background antifibrotic therapy vs patients receiving placebo (1%) and background antifibrotic therapy. In patients not receiving concomitant nintedanib, diarrhea led to treatment discontinuation in 1% of patients treated with JASCAYD at 18 mg and in no patients receiving JASCAYD at 9 mg or placebo. In most patients treated with JASCAYD, diarrhea was of mild to moderate intensity and generally occurred within the first 3 months of treatment.
"The US [FDA] approval of JASCAYD is an important step forward to help slow lung function decline for people living with PPF, providing a new, well-tolerated treatment option," said Shashank Deshpande, chairman of the Board of Managing Directors and Head of Human Pharma at Boehringer Ingelheim.
The FDA-approved product label contains no Warnings and Precautions section. Boehringer Ingelheim will provide access support through its CareConnect4Me patient support program.
Source: PRNewswire
