Incyte (INCY) has announced a significant setback in its early-phase pipeline, pausing enrollment in the Phase 2 study of MRGPRX2 (INCB000262) for chronic spontaneous urticaria (CSU) following the observation of adverse preclinical toxicology findings. The company is collaborating with the U.S. Food and Drug Administration (FDA) to assess the data and determine the future direction of the program. This decision was made public on November 18, 2024.
In addition to the MRGPRX2 setback, Incyte also reported that Phase 2 study results for MRGPRX4 (INCB000547) in cholestatic pruritus (CP) did not support further development, leading to the discontinuation of the program.
MRGPRX2 Program Update
The pause in the MRGPRX2 trial represents a notable challenge for Incyte. Chronic spontaneous urticaria is a debilitating skin condition characterized by the spontaneous appearance of hives and itching, affecting an estimated 0.5% to 1% of the population. Current treatment options, such as antihistamines and biologics like Xolair (omalizumab), do not provide adequate relief for all patients, highlighting the unmet medical need in this space.
While enrollment in other INCB000262 proof-of-concept studies is complete, the data from these studies will be crucial in informing future development decisions and guiding the potential development of back-up molecules. The specific nature of the preclinical toxicology findings has not been disclosed, but such findings at this stage of development often necessitate extensive investigation and can potentially lead to program termination.
MRGPRX4 Program Discontinuation
The discontinuation of the MRGPRX4 program in cholestatic pruritus further impacts Incyte's dermatology and pruritus portfolio. Cholestatic pruritus is a severe itching condition associated with liver disease, significantly impacting the quality of life for affected individuals. The failure of MRGPRX4 to demonstrate sufficient efficacy in Phase 2 trials underscores the challenges in developing effective treatments for this condition.
Impact on Incyte's Pipeline
These developments affect two key programs in Incyte's early-phase pipeline, potentially creating gaps in their future product lineup. The toxicology findings for MRGPRX2 are particularly concerning as they emerged after clinical trials had begun, raising questions about the program's viability. The market for CSU treatments is substantial, with current options including Xolair and other biologics, making this setback more impactful for Incyte's growth prospects.
Incyte remains committed to advancing its pipeline of innovative therapies in oncology and inflammation & autoimmunity. The company will continue to work closely with the FDA to evaluate the MRGPRX2 data and explore potential alternative strategies.
