Gilead Sciences Exits MASH Therapeutics and Liver Disease Pipeline Following Termination of Novo Nordisk Combination Therapy Collaboration

Aug 12, 2025 09:15 CST Updated 09:15

Gilead Sciences

Antiviral Drug Developer

After the release of the Q2 2025 earnings report, Gilead Sciences announced the termination of its MASH (Metabolic Dysfunction-Associated Steatohepatitis, previously known as NASH, Nonalcoholic Steatohepatitis) combination therapy project in collaboration with Novo Nordisk. This project was evaluating the combination of cilofexor and firsocostat with semaglutide for the treatment of MASH. This decision signifies that Gilead has completely cleared its pipeline in fibrotic diseases and will allocate more resources to oncology and other fields, marking a full departure from its long-standing focus on liver disease.

MASH is a complex and progressive liver disease characterized by excessive fat accumulation in the liver accompanied by inflammation. As the condition advances, it can lead to liver fibrosis, and in severe cases, result in scarring of the liver or even progress to end-stage liver disease requiring a liver transplant. Globally, the number of MASH patients is substantial and on the rise. The significant unmet clinical needs have attracted numerous pharmaceutical companies to invest in related drug development, with Gilead Sciences being one of them. Gilead has committed substantial manpower, resources, and finances in an attempt to address this medical challenge, yet the journey of research and development has been fraught with difficulties.

Looking Back at the End of 2019: Gilead's NASH Drug Development Suffered a Major Setback

Faced with such research results, opinions in the industry are divided. Some believe that the study's failure may be due to the small number of patients in each cohort (approximately 30 patients in the firsocostat and cilofexor monotherapy groups, and about 70 patients in the combination therapy group), pointing out that the firsocostat/cilofexor combination therapy group shows some potential. They suggest discussing with regulatory agencies to conduct a larger-scale Phase IIb study. However, J.P. Morgan bluntly declared this another setback for Gilead Sciences in the NASH field, equivalent to yet another project being eliminated. Despite the setback in the critical indicator of liver scarring, Gilead noted that the firsocostat-cilofexor combination therapy achieved statistically significant improvements in other NASH metrics, such as reduced liver enzyme levels and positive outcomes in non-invasive tests for scarring. Additionally, in secondary endpoints including steatosis (liver fat accumulation), inflammation, hepatocyte ballooning, and NAFLD Activity Score (used to measure the activity of fatty liver disease), it performed better than the placebo group.

To break the deadlock in research and development, Gilead turned its attention to external collaborations. As early as April 2019, Gilead reached a clinical collaboration agreement with Novo Nordisk, aiming to integrate their technological and resource advantages in the NASH field. The core of this collaboration was to conduct a proof-of-concept study exploring the feasibility and efficacy of combining Novo Nordisk's semaglutide with Gilead's cilofexor and firsocostat for the treatment of NASH patients. During subsequent research, the collaboration showed positive signs. The two companies announced an expansion of their NASH clinical collaboration, planning to initiate a new Phase IIb double-blind, placebo-controlled study. This study aims to evaluate the safety and efficacy of a fixed-dose combination of semaglutide, Gilead's cilofexor, and firsocostat, used either separately or in combination, in patients with decompensated cirrhosis (F4) caused by NASH. This four-arm study, involving approximately 440 patients, will focus on assessing the treatment's impact on liver fibrosis improvement and NASH regression.

This Phase IIb study was initiated based on the positive results of the Phase IIa proof-of-concept study announced in November 2020. The study evaluated the use of semaglutide alone or in combination with cilofexor/firsocostat in 108 patients with NASH and mild to moderate fibrosis. The results showed that all treatment regimens were well tolerated within 24 weeks, with gastrointestinal issues being the most common adverse events. Post-hoc analysis of exploratory efficacy endpoints for liver health biomarkers revealed statistically significant improvements in hepatic steatosis (measured by MRI-PDFF) and liver injury (measured by serum alanine aminotransferase ALT) in the combination therapy group, surpassing the effects observed in the semaglutide-only group. These early data brought new hope to combination therapies for NASH, generating high expectations in the industry for this therapeutic approach.

But reality did not go as people wished, and Gilead Sciences ultimately announced the termination of this collaborative project. Although a Phase II clinical trial involving 457 patients was completed in December 2024, Gilead Sciences has not yet publicly disclosed any related data, prompting widespread speculation about the reasons.

In addition to making significant adjustments in the field of liver diseases, Gilead has also initiated a cleanup in its oncology pipeline by terminating the development of two early-stage oncology assets: DGKα inhibitor GS-9911 and MCL1 inhibitor zamzetoclax (GS-9716). Both candidates were previously in Phase I clinical trials, aimed at treating patients with advanced solid tumors and advanced solid malignancies, respectively. This major shift in research direction highlights a strategic realignment for Gilead, with the company likely to increase investment in oncology and other areas of strength to seek new growth opportunities. The once highly anticipated liver disease sector, particularly the development of MASH treatments, may become a thing of the past in Gilead's history.

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