Incyte and iTeos Therapeutics have both announced the termination of clinical development programs for zilurgisertib and inupadenant, respectively, following disappointing clinical trial results. These decisions reflect a strategic recalibration in the face of underwhelming data and a renewed focus on more promising assets within their pipelines.
Incyte Discontinues Zilurgisertib Development
Incyte has ceased the development of zilurgisertib, an investigational ALK2 inhibitor, which was being evaluated for myelofibrosis-associated anemia and fibrodysplasia ossificans progressiva. The decision was based on the candidate's "limited efficacy" observed in a Phase I trial, according to William Blair analysts. Zilurgisertib was designed to block ALK2, thereby boosting the production of hepcidin, increasing plasma iron levels, and promoting red blood cell production while suppressing ossification.
BMO Capital Markets noted that this discontinuation adds to a growing list of pipeline setbacks for Incyte. The company had previously indicated that zilurgisertib required higher doses than initially anticipated to achieve promising efficacy, suggesting potential weaknesses in overall activity. Zilurgisertib now joins INCB000547, a MRGPRX4 antagonist, in Incyte’s discontinued programs after Phase II data failed to meet expectations for chronic pruritus.
iTeos Deprioritizes Inupadenant for NSCLC
iTeos Therapeutics has deprioritized the development of inupadenant, a small molecule A2AR blocker, in metastatic non-small cell lung cancer (NSCLC). According to CEO Michel Detheux, the decision stems from Phase II data indicating that the candidate "does not meet a sufficient level of clinical activity to warrant further investment."
The Phase II trial evaluated inupadenant in combination with carboplatin and pemetrexed, yielding a 63.9% overall response rate in post-immunotherapy patients, with a median progression-free survival (PFS) of 7.7 months across all doses. Exploratory analysis suggested that inupadenant treatment restored normal levels of the CXCL3 chemokine, a biomarker associated with clinical activity. Despite these findings, iTeos is redirecting resources to prioritize other "differentiated, first- or best-in-class therapies." The company plans to provide more details on its pipeline strategy in 2025.
