Positive Phase 1 study showed clean safety data and strong response of biomarker
Phase 2a Proof of Concept study in ulcerative colitis will start next month
Mechelen, Belgium; 27 March 2013 – Galapagos NV (Euronext: GLPG) announced today that GLPG0974, an inhibitor of FFA2 (free fatty acid receptor 2, formerly known as GPR43) being developed to treat chronic neutrophil-driven inflammatory conditions such as inflammatory bowel disease (IBD), showed a clean safety profile and a strong biomarker signal. In this second Phase 1 study with GLPG0974, the safety, tolerability, pharmacodynamics and pharmacokinetics were evaluated in 32 healthy volunteers dosed for 2 weeks. The positive outcome of this study supports progression to a Proof of Concept study in ulcerative colitis patients that is expected to start in 2Q 2013.
The completed Phase 1 study evaluated once- and twice-daily dosing regimens in healthy volunteers who received GLPG0974 for 2 weeks. This second Phase 1 study follows the First-in-Human study for GLPG0974 completed in 2012, in which a dose range was given as single doses. The current study confirmed that GLPG0974 was safe and well tolerated at all dose levels. A dose dependent inhibition of neutrophil activation was shown, up to a maintained 24-hour inhibition of the biomarker.
“GLPG0974 is the first FFA2 inhibitor to be tested clinically, and these results are very encouraging,” said Dr Piet Wigerinck, CSO of Galapagos. “The multiple ascending dose study showed stable PK, good safety and tolerability and a good inhibition of biomarker CD11b. The next step is a Proof of Concept study with GLPG0974. The aim of this study will be to show a clinical response in patients with ulcerative colitis. It is expected to start next month.”
Details of the second Phase 1 clinical study
The aim of this study was to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of oral multiple ascending doses of GLPG0974. The randomized, double-blind, placebo-controlled, single center study was conducted in 32 healthy volunteers in Belgium. GLPG0974 was dosed for 2 weeks as once- and twice-daily regimens. The study was designed to confirm the strong biomarker signal previously observed in the First-in-Human Phase 1 study. The biomarker that was measured in blood from healthy volunteers was CD11b, a neutrophil surface marker. The presence of CD11b increases when neutrophils are activated in response to inflammatory stimuli.
About candidate drug GLPG0974
GLPG0974 is an orally available small molecule that reduces migration of neutrophils, one of the critical cell types in inflammatory processes, by potent inhibition of FFA2 (free fatty acid receptor 2, formerly known as GPR43). Overactivity of neutrophils is a cause of tissue damage in illnesses such as inflammatory bowel disease. A reduction of neutrophil activation and migration by inhibition of FFA2 may provide for a novel anti-inflammatory treatment approach. By inhibiting FFA2, GLPG0974 prevents free fatty acid-induced activation and migration of neutrophils towards an inflammatory site, such as in the gut of patients with inflammatory bowel disease. GLPG0974 is the first inhibitor of FFA2 to be evaluated clinically. Galapagos expects to start a Proof of Concept study ulcerative colitis in 2Q 2013.
Inflammatory bowel disease is a group of inflammatory conditions in the small intestine and colon, the main forms being Crohn’s and ulcerative colitis. Crohn’s disease can affect the entire wall in any part of the gastrointestinal tract, while ulcerative colitis affects only the lining in the colon and rectum. Patients suffering from IBD conditions experience abdominal pain, vomiting, diarrhea, weight loss, and rectal bleeding, and may also have symptoms outside the bowel, such as problems with skin, eyes, and liver. Approximately 0.8% of the European population and 0.7% of the North American population is diagnosed annually with IBD. This chronic condition is without a medical cure and commonly requires a lifetime of care. Current drug treatment includes anti-inflammatory steroids and immuno-suppressive agents such as TNF inhibitors. Over the long term, up to 75% of patients with Crohn’s disease and 25% of those with ulcerative colitis will require surgery to remove the inflamed parts of the bowels. In the United States, IBD accounts for more than 700,000 physician visits and 100,000 hospitalizations per year, and disability in 119,000 patients.
Galapagos (Euronext: GLPG; OTC: GLPYY) is specialized in novel modes-of-action, with a large pipeline of four clinical, six pre-clinical, and 30 discovery small-molecule and antibody programs in cystic fibrosis, inflammation, antibiotics, metabolic disease, and other indications.
GLPG0634 is an orally-available, selective inhibitor of JAK1 for the treatment of rheumatoid arthritis and potentially other inflammatory diseases, about to enter Phase 2b studies. AbbVie and Galapagos signed a worldwide license agreement whereby AbbVie will be responsible for further development and commercialization after Phase 2b. Galapagos has another selective JAK1 inhibitor in Phase 2 in lupus and psoriasis, GSK2586184 (formerly GLPG0778, in-licensed by GlaxoSmithKline in 2012). GLPG0187 is a novel integrin receptor antagonist currently in a Phase 1b patient study in metastasis. GLPG0974 is the first inhibitor of FFA2 to be evaluated clinically for the treatment of IBD; this program will start a Proof of Concept Phase 2 study in Q2 2013.
The Galapagos Group, including fee-for-service companies BioFocus, Argenta and Fidelta, has over 800 employees and operates facilities in five countries, with global headquarters in Mechelen, Belgium. Further information at: www.glpg.com
Dr Piet Wigerinck, Chief Scientific Officer
Tel. +32 477 627103
Elizabeth Goodwin, Director Investor Relations
Tel: +31 6 2291 6240
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 Sources: Wikipedia, CDC.gov