Date: 2015-09-22
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the European Respiratory Society Annual Meeting in Amsterdam, Netherlands
Company: Galapagos (Belgium) Janssen Pharmaceutica, a J&J company (USA - NJ)
Product: GLPG1690
Action
mechanism: enzyme inhibitor/autotaxin inhibitor. GLPG1690 has a novel mode of action discovered by Galapagos, with potential application in pulmonary diseases. Galapagos identified autotaxin as playing a key role in inflammation, using an inflammation assay in its unique target discovery platform. Pharmacology and translational studies published by other parties in the literature since then suggest autotaxin may play a key role in metabolic disease, arthritic pain, oncology, and lung disease. In 2007, Galapagos announced an alliance agreement with Janssen Pharmaceutica NV providing the option to worldwide, commercial licenses to certain Galapagos internal inflammatory disease programs. These programs are based on novel targets for inflammatory disorders that were identified and validated by Galapagos using its proprietary target discovery engine. Subsequent Galapagos research led to the discovery of GLPG1690, a first-in-class molecule that entered the clinic for inflammatory disorders. Galapagos is responsible for execution of Phase 1 and Phase 2A studies with GLPG1690. Janssen Pharmaceutica NV and Galapagos have mutually agreed to terminate these inflammation alliance and option agreements in March 2015.
Disease: chronic obstructive pulmonary disease (COPD)
Therapeutic area: Lung diseases - Respiratory diseases
Country: Belgium
Trial
details: The aim of the Phase 1 study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of oral single and multiple ascending doses of GLPG1690. The randomized, double-blind, placebo-controlled, single center study is being conducted in at least 40 healthy volunteers in Belgium. In the first part of the study, single ascending doses will be evaluated. In the second part, the new compound will be administered daily for 14 days.The pharmacokinetics of a solid dosage formulation of GLPG1690 will be compared with those of a liquid dosage formulation of GLPG1690. Also, the potential of cytochrome P450 (CYP)3A4 induction after repeated dosing with GLPG1690 will be explored. (NCT02179502)
Latest
news: * On September 22, 2015, Galapagos announced the presentation of pre-clinical and Phase 1 results for autotaxin inhibitor GLPG1690 at the European Respiratory Society Annual Meeting in Amsterdam, Netherlands. Galapagos expects to file an exploratory Phase 2 study in idiopathic pulmonary fibrosis before year end. GLPG1690 has potential application in other pulmonary diseases such as chronic obstructive pulmonary disease (COPD), as supported by the presentation on pre-clinical findings at ERS this year: "Pharmacological profile and efficacy of GLPG1690, a novel ATX inhibitor for COPD treatment," poster PA2129 in Poster Discussion Session: "New targets and modalities for the treatment of asthma and COPD" Galapagos is the first to show efficacy of an autotaxin inhibitor in pre-clinical models for COPD and IPF, pointing to novel therapeutic areas for autotaxin inhibition. The poster shows how GLPG1690 acts as a potent inhibitor of mouse and human autotaxin (IC50: 100 -500 nM range). Furthermore, GLPG1690 reduces inflammation in a mouse steroid-resistant tobacco smoke model to a similar extent as a standard therapy for COPD. Galapagos also presents the topline results with GLPG1690 in Phase 1 in healthy human volunteers: "Favorable human safety, pharmacokinetics and pharmacodynamics of the autotaxin inhibitor GLPG1690, a potential new treatment in COPD," oral presentation OA484 in session "Advances in the future treatment of COPD" . GLPG1690 was safe and well tolerated up to a single oral dose of 1500 mg and up to 1000 mg twice daily for 14 days, with no significant adverse effects on ECGs, vital signs or laboratory parameters. The compound also showed good oral bioavailability with a half-life of 5 hours and a dose-proportional increase in exposure. GLPG1690 showed concentration-dependent reduction of a relevant biomarker (plasma LPA18:2 levels) with a maximum of approximately 90%. At steady state, continuous reduction of this biomarker levels of >60% was observed from 0 to 24 hours. The presentation will also include relevant pre-clinical model data for COPD and IPF with GLPG1690. * On February 16, 2015, Galapagos announced that GLPG1690, a first-in-class molecule for pulmonary disease, has demonstrated target engagement, a good safety profile, and favorable drug properties in a Phase 1 study. Galapagos is developing GLPG1690 within its alliance with Janssen Pharmaceutica NV. The aim of the Phase 1 study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of oral single and multiple ascending doses of GLPG1690. The randomized, double-blind, placebo-controlled, single center study was conducted in 40 healthy volunteers in Belgium. In the first part of the study, single ascending doses were evaluated. In the second part, the new compound was administered daily for 14 days. GLPG1690 proved to be safe and well-tolerated over a wide dose range in healthy volunteers. Engagement of the thus far undisclosed novel target was confirmed using a relevant biomarker. GLPG1690 displayed a favorable pharmacokinetic and pharmacodynamic profile. The data shown in Phase 1 encourage Galapagos to explore a Phase 2 study design in pulmonary disease. * On July 1, 2014, Galapagos announced that GLPG1690, a first-in-class molecule aimed at treating pulmonary diseases, has been dosed in a Phase 1 First-in-Human study. Galapagos will receive a € 6.6 million milestone payment from Janssen Pharmaceutica NV for this achievement. In 2007, Galapagos announced an alliance agreement with Janssen Pharmaceutica NV providing the option to worldwide, commercial licenses to certain Galapagos internal inflammatory disease programs. These programs include novel targets for inflammatory disorders that were identified and validated by Galapagos using its proprietary target discovery engine. Subsequent Galapagos research led to the discovery of GLPG1690, a first-in-class molecule that entered the clinic for pulmonary disorders. Galapagos is responsible for execution of Phase 1 and Phase 2A studies with GLPG1690.
