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Galapagos FLORA trial targets IPF
MECHELEN, Belgium—Galapagos NV in August announced positive top-line results with its autotaxin inhibitor GLPG1690 in patients with idiopathic pulmonary fibrosis (IPF) in the FLORA Phase 2a trial. FLORA was an exploratory randomized, double-blind, placebo-controlled trial investigating a once-daily 600 mg oral dose of GLPG1690. The drug candidate was administered for 12 weeks in 23 IPF patients, 17 of whom received GLPG1690 and six of whom received placebo. Primary objectives of the trial were to assess safety, tolerability, pharmacokinetics and pharmacodynamics of GLPG1690 in an IPF patient population.
Secondary objectives included the evaluation of lung function, changes in disease biomarkers, functional respiratory imaging (FRI) and quality of life. Patients with previous experience on nintedanib or pirfenidone were required to have discontinued treatment with either agent for at least four weeks prior to initiating treatment with GLPG1690.
“GLPG1690 is a novel, small-molecule inhibitor of autotaxin. Autotaxin was discovered as a target by Galapagos, using our proprietary target discovery platform. Autotaxin plays an important role in the LPA pathway and, as a result, in fibrosis. GLPG1690 is the first drug to show stabilization of lung function during 12 weeks of treatment,” a Galapagos spokesperson tells DDNews. “Patients on placebo saw a decrease of 87 mL FVC [forced vital capacity] decline versus an increase of 8 mL in patients treated with GLPG1690.”
GLPG1690 has shown promising results in relevant preclinical models for IPF, and there is growing evidence in scientific literature that autotaxin plays a role in this disease. GLPG1690 successfully completed a Phase 1 trial in 2015, showing favorable findings relating to safety and tolerability as well as high target engagement in healthy volunteers. Galapagos received Orphan Drug designation for GLPG1690 in IPF from the FDA and European Commission.
In addition, this is the first autotoxin inhibitor to show effect in a 12-week IPF patient trial, according to a Sept. 19 investor presentation from Galapagos. Monotherapy shows stabilization of lung function as measured by FVC, and FRI confirms the FVC data with statistical significance. GLPG1690 was generally well tolerated, and Galapagos believes the results support a rapid move to late-stage trial.
Patients on GLPG1690 treatment showed a clear reduction of serum LPA18:2, a biomarker for autotaxin inhibition, as expected based on the mechanism of action of GLPG1690. Thus, the level of target engagement observed in Phase 1 with healthy volunteers was confirmed in IPF patients in FLORA. Rates of discontinuation due to adverse events, as well as serious adverse event rates, were similar between patients on GLPG1690 and placebo.
“Galapagos’ results with GLPG1690 are extremely exciting and exceed those of previous studies. This brings hope to patients with idiopathic pulmonary fibrosis that new effective treatment may be on the horizon. Importantly, some patients even showed an increase of lung function within only 12 weeks of treatment, and the drug was well tolerated. The results from FLORA beg the question how patients will fare with longer treatment. I urge Galapagos and the IPF community to progress to the next phase of clinical trials as rapidly as possible,” said Dr. Toby Maher, professor of interstitial lung disease at Imperial College London and Consultant physician at Royal Brompton Hospital in London.
Galapagos plans to rapidly progress GLPG1690 in a late-stage trial and has already had discussions with regulators regarding trial design. “We are aiming for late-stage clinical development; this still has to be finalized,” says the Galapagos spokesperson.
“Not only does GLPG1690 show early promise as a potential therapy for IPF, but it also marks an important milestone for Galapagos as a company: proof of concept in patients of a second mechanism of action coming from our target discovery platform. Galapagos has shown that this platform continues to deliver novel mechanisms of action beyond JAK1 in inflammation. The stabilization of FVC over 12 weeks upon GLPG1690 treatment is a major milestone in IPF, where, by way of reference, the currently approved treatments show a decrease of approximately 30 mL over the same treatment period,” added Dr. Piet Wigerinck, chief scientific officer of Galapagos.
Wigerinck said in a webcast from August 10, regarding other potential clinical indications, that “…As we said before, it’s our strategy to do more than one proof-of-concept clinical study with every novel mechanism of action … It will be too soon to report on that today but I can tell you, we are running a number of animal models. And over the coming months, we’ll let you know which is the second indication.”