Gilead 1Q19 – NASH focus turns to phase 2b ATLAS combination therapy trial on heels of two negative phase 3 readouts for selonsertib; Partnerships with Novo Nordisk and others highlighted – May 2, 2019

Executive Highlights

  • Gilead gave its 1Q19 updatetoday. In NASH, Gilead’s 1Q19 was marked first by negative phase 3 resultsfor selonsertib in the STELLAR 4trial (n=877) in F4 fibrosis (compensated cirrhosis) due to NASH, announced in February. Weeks later in April, Gilead also announced negative phase 3 resultsfor selonsertib in the STELLAR 3trial (n=802) of the ASK-1 inhibitor in F3 fibrosis due to NASH. In both trials, selonsertib missed the primary endpoint of ≥1 stage improvement in fibrosis without worsening of NASH at 48 weeks. Management has indicated that it will not further investigate selonsertib as monotherapy for NASH.
  • 1Q19 was a watershed quarter in the NASH competitive landscape, and it seems most likely that Intercept’s obeticholic acidwill become the first-ever therapy approved for NASH. Also in February, Intercept announcedpositive interim results from the phase 3 REGENERATE study on one of two co-primary endpoints in F2/F3 fibrosis due to NASH: The 25 mg dose of OCA improved liver fibrosis with no worsening of NASH, while trending positively but not reaching superiority on NASH resolution with no worsening of fibrosis. The 10 mg dose achieved nominal significance on fibrosis. Intercept will file the FXR agonist with FDA and EMA in 2H19, setting OCA up to potentially become the first approved NASH therapy. Importantly, FDA has agreed that only one co-primary endpoint must be met for approval – and fibrosis is strongly regarded as the more important of the two. Of the phase 3 NASH trials scheduled to report in 2019, only Genfit’s RESOLVE-IT study for elafibranor (dual PPAR agonist) remains outstanding, with topline data scheduled for release late this year. 
  • In Gilead’s own NASH pipeline (see below), the phase 2b ATLAS study is expected to complete in October 2019, and 24-week data are expected in 4Q19 (see the trial design just below). ATLAS is testing combinations of selonsertib, cilofexor (FXR agonist), and firsocostat (ACC inhibitor) in F3-F4 patients. Pending a positive readout from ATLAS, and possiblyeven once 24 week data is in hand, we expect the company to move a combination therapy into phase 3 – though we’re curious how partnerships may impact these plans. Of note, Gilead just presentedpositive proof-of-concept results for a firsocostat/cilofexor combination (n=20) at the International Liver Congress, demonstrating ≥30% reduction in hepatic fat (measured by MRI-PDFF) in 74% of treated patients at 12 weeks.
  • Partnerships have also become a key part of Gilead’s NASH strategy: In January, Gilead announcedit had acquired, from Yuhan, global rights to develop and commercialize two undisclosed small molecules as potential NASH treatments. Moreover, an April partnershipwith Novo Nordisk will see combination trials of GLP-1 agonist Ozempic (semaglutide), FXR agonist cilofexor (GS-9674), and ACC inhibitor firsocostat (GS-0976) in NASH. Finally, a three-year collaborationwith insitro is focused on using machine learning and genomics to discover and develop new NASH therapies. The latter two were highlighted by CMO Dr. John McHutchison during prepared remarks. 

Read on below for Q&A from the call, a summary of Gilead’s entire NASH pipeline, and the phase 3 NASH competitive landscape

ATLAS Trial Design

Gilead NASH Pipeline Summary


Product Details




ASK-1 inhibitor

Phase 3


Selonsertib missed primary endpoint in STELLAR 3 and STELLAR 4 trials in F3 fibrosis and cirrhosis

Firsocostat (GS-0976)

ACC inhibitor

Phase 2

Phase 2 resultspresented October 2017 (trial completed July 2017); Positive proof-of-concept data presented at EASL 2017

Cilofexor (GS-9674)

FXR agonist

Phase 2

Phase 2 trial completed January 2018, presented at The Liver Meeting 2018

Combination regimens

Nine cohorts, each receiving a different combination of selonsertib, GS-0976, and GS-9674

Phase 2a

Data presented at ICL 2019, showing proof-of-concept for firsocostat+cilofexor at 12 weeks; Phase 2 trial of combinations expected to complete July 2019(delayed from May 2018); Data presented at EASLin April 2018

ATLAS: combination regimens

Selonsertib/GS-9674; selonsertib/GS-0976; GS-9476/GS-0976; monotherapies

Phase 2b

Screening closed 3Q18; Expected to complete October 2019, moved up from April 2020; 24-week data expected 4Q19; Targeting 2023 combination regimen approval

Competitive Landscape: Phase 3 NASH Pipeline Summary


Drug Name



Other Remarks

(completion = primary completion date)


Elafibranor (GFT505)

Dual PPAR alpha/gamma agonist

Phase 3

RESOLVE-ITtrial in F1-F3 fibrosis recruiting with completion expected December 2021; Interim results expected in 2019; Phase 2a results reported March 2015

Intercept Pharmaceuticals

Obeticholic acid

FXR agonist

Phase 3

Positive interim results in F2-F3 fibrosis announced February 2019, expected to support 2H19 regulatory filing; REGNERATEand REVERSEtrials in F1-F3 fibrosis and cirrhosis recruiting and expected to fully complete October 2022 and July 2020, respectively


Cenicriviroc (CVC)

CCR2/CCR5 inhibitor 

Phase 3

AURORA trial in F2-F3 fibrosis recruiting with primary completion expected October 2021 (pushed back from July 2019 and Sept. 2020); Acquired from Tobira Therapeutics September 2016


Selonsertib (GS-4997)

ASK-1 inhibitor

Phase 3

Selonsertib missed primary endpoint in STELLAR 3 and STELLAR 4 trials in F3 fibrosis and cirrhosis 

Select Questions and Answers

Q:At this point, how much of a strategic priority would you say the NASH portfolio or the HIV portfolio is, and if the answer is high, how aggressive do you think you want to be on the meeting front to add assets to these two categories?

A:Specifically related to NASH, although the results in the first quarter this year didn't turn out as we had expected, it's very clear that this disease needs scientific advancement. It's a heterogeneous disease, there are challenges with diagnosis, and at the same time, Gilead's expertise in liver disease makes it an area of continued interest for us. I'm particularly interested in the fact that a disease like this with the challenges associated with it may very well require combination therapies, and of course we will have some readouts on our combination approaches in the second half of this year. You heard already from John some of the partnerships that we have on that front. 

Q:You decided to have a collaboration with Novo Nordisk on NASH. How does it compare to the others in that market today are in development today if you look at some glue, data in Nash? Thank you.

A:GLP-1 agonism is a compelling mechanism of action, and Novo Nordisk is clearly a leader in the pharmaceutical development of products for patients with diabetes and metabolic syndrome. The mechanism of action is not necessarily directly related to NASH, but has many of the effects you would want to see in patients with NASH, and additionally and importantly has other metabolic benefits in terms of glucose control, insulin secretion, and a weight-loss component. There is a significant weight-loss component, and we think that is very compelling for us to explore with other mechanisms of action that are really focusing on separate drivers of NASH pathogenesis. So we believe it's a very exciting and a very important collaboration. Novo Nordisk brings a lot of people and a lot of depth of knowledge about metabolic syndrome to the table while we bring a lot of expertise in liver disease. So it's a wonderful collaboration that we are just starting looking forward to. So we will combine semaglutide with our FXR agonist and our ACC drug as well, and that will be the initial collaboration.


--by Ann Carracher and Kelly Close