Monday, December 3, 2012

Monoclonal antibody GS-6624 well tolerated by patients with hepatic fibrosis in initial safety study

Monoclonal antibody GS-6624 well tolerated by patients with hepatic fibrosis in initial safety study

December 3, 2012
BOSTON — Patients with hepatic fibrosis treated with monoclonal antibody GS-6624 experienced reductions to AST and ALT levels with no serious adverse events, treatment discontinuations or dose adjustments in a study presented at The Liver Meeting.

In a trial assessing the safety of GS-6624 in patients with liver disease, researchers administered three 1-hour infusions of 10 mg/kg (mean dose 806.5 mg per infusion), each separated by 2 weeks, to 10 patients (nine men), with a mean Metavir fibrosis stage of 2.1 (range 1-3). A 6-week follow-up period occurred after study completion. Nine patients had chronic HCV, four had HIV/HCV coinfection and one had nonalcoholic steatohepatitis and HIV.

“This study involved the use of a monoclonal antibody … which targets lysyl oxidase-like 2, which is an enzyme that promotes cross-linking of type 1 collagen in all types of fibrosis; in the liver as well as other entities,” researcher Andrew H. Talal, MD, MPH, chief of gastroenterology and hepatology and professor of medicine at The State University of New York, Buffalo, told “This is the first use in human liver disease.”

All participants completed treatment with no interruptions or dose reductions. Mean levels of ALT, AST and gamma-glutamyltransferase decreased in all patients during treatment, with levels returning to baseline upon completion. Four patients with elevated ALT levels upon treatment initiation experienced a mean ALT decrease of 22% after two infusions.

Nine patients reported 28 adverse events, including abdominal pain (five patients), headache, fatigue and musculoskeletal pain (two patients each); no serious events were reported. Investigators also noted that no patients developed worsening liver enzymes while being treated.

A second cohort, which will receive a slightly lower dose of GS-6624, has since been fully enrolled, and investigators plan to present study results in 2013, along with the results of fine-needle aspirations performed before and after treatment in both sets of patients. Eight of the initial 10 patients also are involved in a 6-month extension study. Each patient receives 700 mg GS-6624 biweekly.

“There were no dose interruptions, adjustments, early discontinuations or SAEs in the first 10 patients in whom we used it,” Talal said. “This is a new paradigm in terms of treatment of fibrosis in liver disease, and one that maybe … underlies various etiologies: Wilson’s disease, NASH, autoimmune hepatitis, hepatitis B and C; it may form a common mechanism by which liver disease of diverse etiologies might be treated.”

Disclosure: The researchers report numerous financial disclosures.

For more information:
Talal AH. P1305: A Monoclonal Antibody Directed at the Lysyl Oxidase-Like 2 (LOXL2) Enzyme Appears Safe and Well Tolerated in Patients With Liver Disease. Presented at: The Liver Meeting 2012; Nov. 9-13, Boston.

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