NHLBI and FAP Target 18F-FAPI-74 for Cardiopulmonary Fibrosis Diagnosis Phase 3 Trial Initiated
Clinical Design and Key Objectives
The National Heart, Lung, and Blood Institute (NHLBI) is recruiting for a Phase 3 trial (NCT07613099) to image active cardiopulmonary fibrosis using 18F-FAPI-74 PET/CT. The unbranded 18F-FAPI-74 is an 18-fluorine-labeled fibroblast activation protein inhibitor, with the target molecule being fibroblast activation protein (FAP). The trial will enroll 210 adults at the NIH Clinical Center and compare the fibrosis detection performance of non-contrast chest CT, 18F-FDG PET/CT, and cardiac MRI in a fibrosis cohort. The trial is scheduled to start in August 2026 and conclude in May 2031, emphasizing long-term diagnostic validation over short-term regulatory events.
Clinical Value Differing from Existing Imaging
CT and cardiac MRI effectively visualize accumulated scarring and structural changes but differ in their ability to directly measure ongoing fibroblast activity. 18F-FAPI-74 binds to FAP on activated fibroblasts to capture dynamic fibrosis signals in interstitial lung disease, lung transplantation, acute lung injury, pulmonary arterial hypertension, and cardiovascular disease. The trial will repeatedly evaluate imaging and blood biomarkers over up to two years to analyze disease progression and treatment response. Success could establish 18F-FAPI-74 as a companion biomarker for selecting patients to initiate or modify antifibrotic therapy.
Competitive Landscape and Regulatory Context
The direct comparator, 18F-FDG PET/CT, measures inflammation and glucose metabolism, while CT and MRI assess anatomical damage, making FAP-based imaging a complementary competitor. In the treatment market, Ofev (nintedanib, a VEGFR·FGFR·PDGFR tyrosine kinase inhibitor), Esbriet (pirfentanil, a TGF-β-related fibrosis signaling inhibitor), and Jascayd (neldénimast, a PDE4B inhibitor) are key benchmarks. The FDA received a positive advisory committee recommendation for Esbriet in March 2010 and approved Esbriet and Ofev for IPF in October 2014. Jascayd was approved for IPF in October 2025 and for progressive pulmonary fibrosis in December 2025. 18F-FAPI-74 is currently a research-use Phase 3 diagnostic radiopharmaceutical, with a distinct regulatory pathway.
Commercialization and Market Implications
SOFIE Biosciences retains rights to 18F-FAPI-74 in the U.S., while GE HealthCare Technologies (GEHC) secured development, manufacturing, and commercialization rights outside the U.S. via a contract in October 2023. The agreement is exclusive but does not include upfront payments, milestones, royalties, or equity investment for the NHLBI trial itself, so no deal value is disclosed. The global PET radiotracer market is projected to reach approximately USD 3.2 billion in 2025 and USD 5.8 billion in 2032, with Ofev's 2025 sales alone reaching EUR 3.825 billion. Therefore, clinical validation could serve as a turning point to expand FAPI imaging from its tumor-focused applications into the multi-billion-dollar fibrosis diagnostic and treatment monitoring space.
The 210-patient Phase 3 trial is the first late-stage cardiopulmonary study to validate whether 18F-FAPI-74 detects active fibrosis more effectively than CT, 18F-FDG PET/CT, and cardiac MRI. Positive results would enhance the commercial asset value of SOFIE Biosciences and GE HealthCare Technologies (GEHC). Researchers could secure tools for patient selection and early efficacy assessment in antifibrotic trials by linking FAP signals with blood biomarkers and disease progression. The industry sees an opportunity to connect the 2025 USD 3.2 billion PET radiotracer market and Ofev's EUR 3.825 billion in 2025 sales, which reflect treatment demand. However, the 2031 completion timeline indicates that revenue contribution will be a mid-to-long-term issue. In the short term, recruitment speed and diagnostic performance relative to standard imaging are key, while mid-to-long-term value will depend on establishing reproducibility and clinical performance for FDA approval and quantifying response to Esbriet, Ofev, and Jascayd.
Source: ClinicalTrials.gov (api_ct)