” We were very impressed by the additional insights FRI brought to this clinical trial. The FRI data gave us confidence in the potential of this drug, supporting the signal observed in the lung function measurements. This type of information is very valuable when designing the next clinical trials for this compound.”
Dr Piet Wigerinck, Chief Scientific Officer of Galapagos.
- FRI confirmed the observed signal in Forced Vital Capacity with statistical significance after 12 week treatment with GLPG1690 compared to placebo
- GLPG1960 is a novel autotaxin inhibitor developed by Galapagos aimed at slowing down IPF disease progression
- FRI facilitates IPF drug development in smaller, well powered studies
FLORA was an exploratory, randomized, double-blind, placebo-controlled trial investigating a once daily oral dose of GLPG1690. The drug candidate was administered for 12 weeks in 23 IPF patients, 17 of whom received GLPG1690 and 6 placebo. While the primary objectives of the trial were to assess safety, tolerability, pharmacokinetics and pharmacodynamics of GLPG1690 in an IPF patient population, the study also assessed changes in FRI parameters, lung function, disease biomarkers and quality of life.
The study demonstrated absence of lung function decline over the 12 week treatment period with more sensitive functional respiratory imaging (FRI) parameters confirming the observed disease stabilization in the GLPG1690 arm, versus disease progression in the placebo arm. Two FRI parameters, specific airway volume and specific airway resistance, were significantly (p < 0.05) different between the treatment and placebo arm. The fact that FRI parameters reached statistical significance sooner than conventional endpoints confirms the enhanced power of FRI compared to lung function measures which can be more variable due to the required patient participation. More sensitive endpoints allow for smaller clinical trials which is highly beneficial in an orphan disease such as IPF where number of patients is limited but mortality is high.
“We are very excited to see that these study results confirmed the potential of FRI to develop drugs using smaller clinical trials. This will significantly accelerate the development of better treatments in a disease with a high unmet medical need.” said Dr Jan De Backer, Chief Executive Officer of FLUIDDA.
FLUIDDA will continue the dialogue with the regulators to pursue biomarker approval for FRI in the IPF indication.
Figure 1. Functional Respiratory Imaging (FRI) yields highly accurate, regional information related to fibrosis (green), emphysema (black), blood vessels (red) and airways (blue)
About Functional Respiratory Imaging
Functional Respiratory Imaging (FRI) is a novel image based diagnostic that combines imaging techniques such as High-Resolution CT scans (HRCT) and flow simulations (Computational Fluid Dynamics – CFD). This combination yields 3D visualization and regional quantification of the patient’s lung structure and lung function. FRI provides unparalleled insights in to the respiratory system and helps drug developers develop better drugs more rapidly and assists clinicians in selecting the most optimal treatment for individual patients. Fri has been successfully applied in IPF, asthma, COPD, CF and Lung Transplantation.
GLPG1690 is a small molecule, selective autotaxin inhibitor which is fully proprietary to Galapagos. Galapagos identified the autotaxin target using its proprietary target discovery platform and developed molecule GLPG1690 as an inhibitor of this target. GLPG1690 showed promising results in relevant pre-clinical 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, and high target engagement in healthy volunteers. Galapagos received orphan drug designation for GLPG1690 in IPF from the U.S. Food & Drug Administration (FDA) and European Commission (EC). GLPG1690 is an investigational drug and its efficacy and safety have not been established.
IPF is a chronic, relentlessly progressive fibrotic disorder of the lungs that typically affects adults over the age of 40. There are approximately 200,000 patients with IPF in the U.S. and Europe, with 75,000 newly diagnosed patients per year. As such, IPF is considered a rare disease. The clinical prognosis of patients with IPF is poor as the median survival at diagnosis is 2 to 5 years. Currently, no medical therapies have been found to cure IPF. The medical treatment strategy aims to slow the disease progression and improve the quality of life. Lung transplantation may be an option for appropriate patients with progressive disease and minimal comorbidities.
Regulatory agencies have approved Esbriet®1 (pirfenidone) and Ofev®2 (nintedanib) for the treatment of IPF. Both pirfenidone and nintedanib have been shown to slow the rate of lung function decline in IPF and are likely to become the standard of care worldwide. These regulatory approvals represent a major breakthrough for IPF patients; yet neither drug improves lung function, and the disease continues to progress in the majority of patients despite treatment. Even though FVC was used as the primary endpoint, it is not considered a validated endpoint by FDA. Regulators therefore continue to encourage the exploration of sensitive biomarkers measuring disease stage and biological response to treatment to facilitate clinical development decisions and accelerate drug development.