Gilead posts combo NASH data from biotech buyouts

As the International Liver Congress kicks off in Vienna, Big Biotech Gilead Sciences is one of the first players to reveal its nonalcoholic steatohepatitis data.

Don’t get too excited. The data are out from a very small (just 20 patients) test and are very topline (more data out “later this year”), but here’s the low-down: The midstage, proof-of-concept trial was combining two of Gilead’s NASH assets, a selective, non-steroidal farnesoid X receptor (FXR) agonist cilofexor (aka GS-9674, from its Phenex buy) and the acetyl-CoA carboxylase (ACC) inhibitor firsocostat (aka GS-0976, which came from its Nimbus deal).

Details are thin, but Gilead said in a release that this combo saw improvements in hepatic steatosis, liver stiffness, liver biochemistry and serum fibrosis (scarring) markers.

In the study, 20 patients with the fatty liver disease got both cilofexor 30 mg and firsocostat 20 mg orally, once a day, for 12 weeks.

“A significant decline of at least 30 percent in hepatic fat measured by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) from baseline to 12 weeks was observed in 74% of patients”, the Big Biotech said, with “improvements in liver biochemistry tests including serum ALT (median relative reduction, -37%; p<0.001) and GGT (-32%; p<0.001), along with markers of reduced bile acid synthesis, were observed at 12 weeks.”

Treatment was “well tolerated” with no cases of itching (a potential problem in liver disease trials), with asymptomatic, grade 3 hypertriglyceridemia (higher levels of fat in the blood) seen in two patients.

“NASH is a complex disease with multiple biological pathways that influence its progression. Combination therapeutic approaches which target these pathways, are likely to be needed to effectively treat patients living with NASH, particularly those with advanced fibrosis who have the greatest unmet need,” said John McHutchison, M.D., chief scientific officer and head of R&D at Gilead.

“We are encouraged by the results of our proof-of-concept study being presented this week and look forward to sharing further combination data from the phase 2 ATLAS trial later this year.”

This release comes after the Californian company confirmed this week it is slashing 150 sales force jobs, or about 20% of its workforce in that area, as it looks to save some cash.

While cancer has become a major focus for Gilead after its recent $12 billion buyout of CAR-T maker Kite Pharma, NASH still represents a big pipeline hope for the biotech. But the company has tripped up along the way (as have most of its rivals) in getting a drug, a combo therapy, onto the market for a disease that could be worth up to $40 billion a year at peak.

Just two months back, Gilead was rocked when a phase 3 trial of its big NASH prospect selonsertib bombed. The ASK1 inhibitor was no better than placebo at improving fibrosis, wiping out hopes that selonsertib would spearhead Gilead’s push into a new market.

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It did have better luck when it posted data for firsocostat (then just GS-0976) back in 2017. The data showed a higher dose of its drug saw statistically significant reductions in liver fat in the phase 2 test. But, as ever with NASH, and with Gilead of late, there was a catch: The lower dose missed the mark.

Gilead also revealed data for cilofexor late last year, showing that the FXR agonist improved liver biochemistry and cholestasis—in which bile flow from the liver stops or slows down—in patients with primary sclerosing cholangitis, a rare, chronic liver condition that has no approved treatments.