Pulmonary fibrosis (PF) is a chronic, progressive lung disease characterized by the irreversible scarring of lung tissue. This scarring, or fibrosis, stiffens the lungs and severely impairs their ability to transfer oxygen into the bloodstream, leading to shortness of breath and a persistent, dry cough. The most common and severe form is Idiopathic Pulmonary Fibrosis (IPF), which has an unknown cause and a particularly poor prognosis. While existing treatments can help manage the condition, they do not offer a cure, meaning the disease continues to worsen over time. The development of new pharmacological approaches is continuously sought to slow the decline in lung function for patients.
Contextualizing Pulmonary Fibrosis Treatment
For more than a decade, the treatment landscape for IPF was defined by two primary antifibrotic medications: nintedanib and pirfenidone. These established drugs function by targeting pathways involved in the fibrotic process, demonstrating the ability to slow the rate at which lung function declines in patients with IPF.
Nintedanib operates as a tyrosine kinase inhibitor, blocking multiple cellular pathways that promote scar tissue formation. Pirfenidone possesses anti-inflammatory and antifibrotic properties, although its exact mechanism of action is not completely understood. Neither medication can reverse existing lung damage, but they remain the therapeutic standard for managing disease progression. The limited number of options and the side effect profiles of these drugs highlight the need for new agents with different mechanisms.
Identifying the Latest Approved Therapy
The newest drug approved by the U.S. Food and Drug Administration (FDA) for IPF treatment is Nerandomilast, marketed under the brand name Jascayd. This oral medication was approved in 2025, marking the first novel therapy introduced for this patient population in over ten years. The approval provides a third therapeutic option in a disease area that has seen little change.
Nerandomilast is indicated for use in adults diagnosed with Idiopathic Pulmonary Fibrosis. Its regulatory status was fast-tracked through Priority Review and Breakthrough Therapy Designation. The drug can be prescribed as a standalone therapy or in combination with previously approved antifibrotic agents, offering flexibility in treatment planning.
Mechanism of Action and Clinical Efficacy
Nerandomilast functions as a preferential inhibitor of phosphodiesterase 4B (PDE4B). This mechanism modulates the cellular environment, providing both antifibrotic and immunomodulatory effects. By inhibiting the PDE4B enzyme, the drug influences signaling molecules that promote inflammation and the production of scar tissue.
The drug’s effectiveness was established through the FIBRONEER-IPF Phase 3 clinical trial, a randomized, placebo-controlled study involving adults with IPF. The primary endpoint measured was the change from baseline in Forced Vital Capacity (FVC) over a 52-week period. FVC measures the maximum amount of air a person can forcefully exhale and is the standard metric for tracking lung function decline in IPF.
Results demonstrated that patients receiving the 18 mg dose of Nerandomilast experienced a smaller decline in lung function compared to those on a placebo. The adjusted mean decline in FVC for patients on the active drug was approximately 106 milliliters (mL) over 52 weeks, compared to a 170 mL decline in the placebo group. This 64 mL difference indicates that the treatment slowed the progression of the disease. A positive treatment effect began to appear as early as two weeks after starting the 18 mg dosage.
Patient Suitability and Safety Profile
Nerandomilast is approved for use in adult patients diagnosed with IPF. The recommended starting dosage is 18 milligrams (mg) taken orally twice daily, ideally separated by twelve hours. If patients experience difficulties tolerating the medication, the dosage may be reduced to 9 mg twice daily, though this adjustment is not recommended if the patient is also taking pirfenidone.
The most commonly reported side effects included gastrointestinal issues such as diarrhea and nausea, decreased appetite, and fatigue. Other frequent adverse events were upper respiratory tract infections and depression. A small percentage of patients discontinued the drug due to adverse reactions, with diarrhea being the most common reason. Unlike some other antifibrotic agents, the prescribing information does not require routine liver enzyme monitoring, which simplifies the patient management process.