Drug Development

Promising or inconclusive? Gilead fields PhII GS-4997 data, triggering more pushback on NASH claims

Gilead posted a detailed snapshot of Phase II efficacy data for GS-4997, now known as selonsertib, for NASH and liver fibrosis, triggering a mixed response of enthusiasm and some clear skepticism from the analysts watching this late-stage drug, some of whom got their first crack in when Gilead outlined the top line data from this study in October.

The numbers were detailed for selonsertib alone, in combination with simtuzumab or in simtuzumab alone. And investigators had a mixed bag of results underscoring drug activity, ranging from the 43% of patients taking selonsertib seeing an improvement in fibrosis compared to the 20% in the simtuzumab arm to the 20% in the selonsertib arm experiencing a minimum 15% reduction in liver stiffness to the 32% in the combo group and none taking simtuzumab alone.

Phase 2 Data for Selonsertib in Nonalcoholic Steatohepatitis (NASH) Presented at The Liver Meeting® 2016.

Phase 2 Data for Selonsertib in Nonalcoholic Steatohepatitis (NASH) Presented at The Liver Meeting® 2016.


Gilead $GILD acknowledged earlier this month that simtuzumab has been a bust in the clinic, prompting its R&D team to drop it completely. It also has GS-9674 in early-stage studies for NASH and recently picked up another program from Nimbus. And NASH remains a key feature in the pipeline as Gilead looks to overcome the hangover from its hep C bash, where revenue is now declining steadily.

Brian Skorney, Baird

Brian Skorney, Baird

Even last month, though, analysts like Brian Skorney at Baird were shaking their head over what Gilead had to offer:

“The numbers are too small, the duration of treatment is too short and the data is complicated by the inclusion of another drug instead of placebo.”

After its stunning success with hep C, Gilead’s R&D strategy in general has come under frequent attack as skepticism grows about its ability to overcome its growing problems on the revenue side of the business.

Rohit Loomba, the lead study author and director of the NAFLD Research Center, had this to say in a statement:

“After only 24 weeks of therapy, selonsertib exhibited promising anti-fibrotic activity in this study, which was the first known multi-center NASH clinical trial to use centrally-assessed MRE, MRI-PDFF, in addition to liver biopsy as endpoints. Based on these data, selonsertib represents an important investigational drug candidate for further clinical trials in patients with NASH and significant fibrosis.”

Geoffrey Porges, Leerink

Geoffrey Porges, Leerink

Well, maybe, responds Leerink’s Geoffrey Porges, who notes that this is the study that prompted Gilead to go big in Phase III:

“In their most recent earnings conference call the company disclosed that the product has failed in development in other indications such as diabetic nephropathy, and parallel programs in these liver diseases, including simtuzumab, have also been discontinued. However, management’s reaction to GS4997 was very positive and suggested impressive phase II results. Our reaction to the phase II results is that they do show encouraging signs of disease activity, but at this stage regard the evidence of benefit, and safety and tolerability, as inconclusive. The evidence of effect is persuasive on some endpoints, but unclear on others, and the NASH field is likely to require continued research to refine trial endpoints and to establish some meaningful correlation between those endpoints and clinical benefit for patients. GS4997 also appears to have some tolerability liabilities, which could add to the drug’s limitations in both development and commercialization.”

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Sr. Manager, Regulatory Affairs, CMC
CytomX Therapeutics San Francisco, CA
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Catalytic Data Science Charleston, SC
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Flatiron Health New York City or San Francisco

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