Gilead Announces Top-Line Phase 2 Results for GS-4997 (Selonsertib) in Nonalcoholic Steatohepatitis (NASH), Pulmonary Arterial Hypertension (PAH) and Diabetic Kidney Disease (DKD)
Gilead Sciences, Inc. (Nasdaq:GILD) today announced the top-line results from three Phase 2 studies of GS-4997 (selonsertib), an investigational inhibitor of apoptosis signal-regulating kinase 1 (ASK1), in nonalcoholic steatohepatitis (NASH), pulmonary arterial hypertension (PAH) and diabetic kidney disease (DKD). GS-4997 demonstrated anti-fibrotic activity in an open-label Phase 2 clinical trial that included 72 patients with NASH and moderate to severe (F2-F3) liver fibrosis, who received treatment with GS-4997 (18 mg or 6 mg orally once daily) alone or in combination with simtuzumab (SIM), an investigational antibody directed against lysyl oxidase-like-2 (LOXL2), or SIM alone (125 mg administered via weekly subcutaneous injections) for 24 weeks. Top-line efficacy data for fibrosis-related endpoints from 67 evaluable patients are summarized in the table below. Complete results will be presented at The Liver Meeting® 2016 in Boston.
Endpoint (Week 24)
GS-4997 18 mg
GS-4997 6 mg
|Fibrosis Improvement ≥1 Stage from Baseline*||43% (n=13/30)||30% (n=8/27)||20% (n=2/10)|
|Progression to Cirrhosis||
*Fibrosis staged according to the NASH Clinical Research Network (CRN) classification by a central pathologist blinded to treatment group.
Overall, GS-4997 was well tolerated with no dose-related increase in the incidence of treatment-emergent adverse events or serious adverse events. The most common adverse events were headache, nausea and sinusitis.
“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, PhD, Executive Vice President, Research and Development and Chief Scientific Officer, Gilead Sciences. “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 3 clinical trial program of GS-4997 in patients with NASH.”
Separately, a Phase 2 study of GS-4997 in PAH did not achieve its primary endpoint and a Phase 2 study in DKD did not achieve its primary endpoint based on a preliminary analysis. Due to insufficient evidence of efficacy, Gilead has decided not to pursue Phase 3 studies of GS-4997 in PAH or DKD at this time. Data from these studies will be submitted for presentation at upcoming scientific conferences.
About the GS-4997 Phase 2 Studies
Study GS-US-384-1497 was a Phase 2, randomized, open-label clinical trial designed to evaluate the safety, tolerability and efficacy of GS-4997 alone or in combination with simtuzumab in 72 patients with NASH and fibrosis stages F2-F3. Eligible patients were randomized (2:2:1:1:1) to receive GS-4997 6 mg (n=20), GS-4997 18 mg (n=22), GS-4997 6 mg plus simtuzumab 125 mg (n=10), GS-4997 18 mg plus simtuzumab 125 mg (n=10) or simtuzumab 125 mg alone (n=10) for 24 weeks. GS-4997 was administered orally once daily and simtuzumab was administered via weekly subcutaneous injection. Since no differences were observed between combination and monotherapy, data in the table above are presented by GS-4997 treatment group only.
Study GS-US-223-1015 was a Phase 2 double-blind, placebo-controlled, dose-ranging study evaluating the efficacy, safety and tolerability of GS-4997 in 334 patients with type 2 diabetes mellitus and Stage 3 or 4 renal impairment and albuminuria. Eligible patients were randomized (1:1:1:1) to receive GS-4997 doses of 2 mg (n=81), 6 mg (n=84), 18 mg (n=84) or matching placebo (n=85) once daily on top of DKD background therapy for 48 weeks. The primary endpoint was change in estimated glomerular filtration rate (eGFR) from baseline at Week 48.
ARROW was a Phase 2, dose-ranging, randomized, double-blind, placebo-controlled study designed to determine the safety, efficacy and tolerability of three doses of GS-4997 in 151 patients with PAH (WHO Group 1). Patients were randomized (1:1:1:1) to receive placebo or GS-4997 doses of 2 mg, 6 mg or 18 mg administered once daily on top of stable PAH therapy. The primary endpoint was change from baseline versus placebo in pulmonary vascular resistance (PVR) at Week 24, as measured by right heart catheterization.
Further information about these studies can be found at www.clinicaltrials.gov .
GS-4997 and simtuzumab are investigational products and have not been determined to be safe or efficacious.
GS-4997 is an investigational small molecule inhibitor of apoptosis signal-regulating kinase 1 (ASK1), a protein that promotes inflammation, apoptosis (cell death) and fibrosis in settings of oxidative stress. Oxidative stress normally occurs at low levels in healthy states, but can be increased in many pathological conditions such as NASH.
About Gilead’s Clinical Programs in NASH
Gilead is advancing a pipeline of novel investigational therapies for the treatment of NASH with advanced fibrosis. Gilead is currently planning or conducting Phase 2 and Phase 3 clinical trials evaluating single-agent and combination therapy approaches against multiple core pathways associated with NASH – metabolic dysfunction, inflammation and fibrosis.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate its Phase 3 clinical trial program evaluating GS-4997 in patients with NASH in the currently anticipated timelines or at all. In addition, there is the possibility of unfavorable results from further clinical trials involving GS-4997, including in patients with NASH. Further, it is possible that Gilead may make a strategic decision to discontinue development of GS-4997 if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. As a result, GS-4997 may never be successfully commercialized. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2016, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
For more information on Gilead Sciences, please visit the company’s website at www.gilead.com , follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
Gilead Sciences, Inc.
Sung Lee, 650-524-7792
Nathan Kaiser, 650-522-1853
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