Gilead drops PAH, DKD tests after PhII failure; highlights positive noises for NASH

Gilead ($GILD) will not bother to start late-stage studies of its experimental pulmonary arterial hypertension (PAH) and diabetic kidney disease (DKD) drug after it failed in Phase II studies.

In a brief update, Gilead said its GS-4997 (selonsertib), an investigational inhibitor of apoptosis signal-regulating kinase 1, missed its primary endpoints in two studies for both PAH and DKD.

“Due to insufficient evidence of efficacy, Gilead has decided not to pursue Phase III studies of GS-4997 in PAH or DKD at this time,” the Big Biotech said in a statement. Specific data will be presented “at upcoming scientific conferences.”

Fortunately for the co, these failures did not extend into its test for nonalcoholic steatohepatitis (NASH), also known as non-alcoholic fatty liver disease, where selonsertib “showed anti-fibrotic activity” in an open-label Phase II study.

Detailed data weren’t given, but it looked at 72 patients with NASH and moderate to severe liver fibrosis (scarring), who were given Gilead’s med (18-mg or 6-mg orally once daily) alone or in combination with Gilead's simtuzumab (SIM)--an investigational injected antibody directed against lysyl oxidase-like-2, or that drug on its own alone for 24 weeks.

In the top-line data, Gilead said that after 24 weeks, the 18-mg formulation of its med with SIM showed a fibrosis improvement ≥1 stage from baseline of 43% (n=13/30), while a 6-mg version with SIM hit 30% (n=8/27). SIM alone only got 20% (n=2/10).

When it came to progression to cirrhosis, 18-mg GS-4997 and SIM was 3% (n=1/30); 6-mg with SIM was 7% (n=2/27); and 20% (n=2/10) for SIM alone.

SIM has seen problems this year when it failed tests in cancer and idiopathic pulmonary fibrosis. The numbers are small and the test open-label, and more will need to be done to show just how well this med works in NASH. 

Full data will be shown at The Liver Meeting in Boston next month, but the company is now seeking a late-stage study for this med in fatty liver disease--a potential $40 billion market with a number of biopharmas all in a race to be first to market.

Unsurprisingly, Gilead did not want to talk about the failed studies, but focused on the relatively positive noises from its NASH test.

“We are committed to advancing our pipeline of investigational molecules that separately target metabolic dysfunction, inflammation and/or fibrosis associated with NASH,” said Norbert Bischofberger, CSO at Gilead.

“We are encouraged by these data demonstrating the anti-fibrotic effect of GS-4997 in patients with NASH after only 24 weeks of treatment, and look forward to sharing the complete results with the hepatology community. Additionally, pending discussions with regulatory agencies, we plan to initiate a Phase III clinical trial program of GS-4997 in patients with NASH.”

Hep C 

Gilead also announced updated data from across four Phase III studies of its once-daily, fixed-dose combo of Sovaldi (sofosbuvir), velpatasvir and voxilaprevir across a broad range of Hep C patients with genotypes 1 through 6.

The treatment, also known as SOF/VEL/VOX, across a number of iterations managed to hit SVR12 rates of between 90% to 98% after 12 weeks. While the POLARIS-1, POLARIS-3 and POLARIS-4 studies hit their targets, one test, POLARIS-2 did not meet its primary endpoint.

Gilead said in a statement: “With a pre-specified 5% margin, the SVR12 rate for patients receiving treatment with SOF/VEL/VOX for eight weeks [in POLARIS-2] was not statistically non-inferior to the SVR12 rate for patients receiving SOF/VEL for 12 weeks.”

But the data were still strong enough in Gilead’s eyes to warrant a marketing attempt. “Based on these Phase III results, we plan to submit regulatory applications for SOF/VEL/VOX for the treatment of chronic HCV in the United States in the fourth quarter of 2016 and shortly thereafter in Europe,” said Bischofberger.

The positives seemed to outweigh the negatives for investors, as its shares climbed nearly 2% after midday on the news.