Gilead Launches Sequencing Spree After Phase III NASH Flop

Gilead Launches Sequencing Spree After Phase III NASH Flop
Unhealthy Liver Anatomy Illustration. 3D render

Gilead Sciences is turning to gene sequencing to refresh its nonalcoholic steatohepatitis (NASH) pipeline. The company is collaborating with Renown Institute for Health Innovation (Renown IHI) to sequence 15,000 people with NASH and nonalcoholic fatty liver disease. That data, and more, will then be compared to data from 40,000 healthy Nevada residents gathered by Renown IHI.

“Combining the sequencing of protein coding DNA, with extensive electronic health record data will enable a deep analysis of the roles of genetics and environment in NASH incidence and progression,” said John McHutchison, M.D., chief scientific officer and head of research and development, Gilead Sciences. Notably, participants may also benefit directly from this sequencing program. “Any genetic variants identified in participants through the collaboration may be shared with [them] for patient care purposes,” said Anthony Slonim, MD., DrPH, president and CEO, Renown Health.

Gilead’s high hopes for selonsertib, an ASK-1 inhibitor, were recently dashed by disappointing results from the STELLAR-3 study, which looked at its potential for bridging fibrosis due to nonalcoholic steatohepatitis.

This is a major blow, since NASH is a large untapped market. Estimates of its prevalence are shaky, because of uneven data. But The National Institutes of Health has estimated that between 3% and 12% of U.S. adults suffer from this condition or earlier stages of it. That’s roughly 10 million to 30 million people.  Some drug companies have calculated that it represents an estimated $35 billion market.

Gilead has invested heavily in this field and does not seem deterred.  It has three compounds, selonsertib, cilofexor, and firsocostat, it hopes will be approved alone or in combination. “We believe that effective therapy for NASH will ultimately require a combination approach that targets distinct pathways involved in the pathogenesis of this disease,” said McHutchison in a company release. Data from the Phase 2 ATLAS combination trial of the three drug candidates in patients with advanced fibrosis due to NASH, is anticipated later this year

Now, Gilead is adding a new instrument to their R&D toolbox – their sequencing project with Renown IHI.

Renown IHI is a collaboration between Nevada’s Desert Research Institute (DRI), and Renown Health, a locally governed and owned, not-for-profit integrated healthcare network serving Nevada, Lake Tahoe and northeast California. DRI specializes in investigating the effects of natural and human-induced environmental change and advancing technologies. Renown Health, meanwhile, maintains electronic health records for 1.02 million registered patients. In 2016, Renown and DRI established the Healthy Nevada Project (HNP), which they describe as “the nation’s first community-based population health study.” That project currently comprises 40,000 participants.

In 2017 HNP began a partnership with personal genomics firm Helix to leverage its population health services, exome sequencing, and consumer engagement tools. The HNP is now an ongoing collaboration between Renown IHI, DRI, and Helix. HNP combines genetic, environmental, social and clinical data to address individual and community health needs with the goal of improving health across the state and the nation.

“The analysis of these large datasets in collaboration with Renown IHI could help identify genetic variants that impact the risk of developing NASH and thereby advance the discovery and development of new treatments for this disease,” said McHutchinson.