Galapagos Stopping ISABELA Phase 3 Program of Ziritaxestat in Treating IPF

Galapagos and Gilead Sciences have suspended the worldwide ISABELA Phase 3 program investigating the potential of oral ziritaxestat (GLPG1690) to treat people with idiopathic pulmonary fibrosis (IPF).

The decision to halt the program, which includes two identical Phase 3 trials — ISABELA 1 (NCT03711162) and ISABELA 2 (NCT03733444) — was based on recommendations of the independent data monitoring committee overseeing the studies.

After reviewing data from both trials, the committee concluded that the potential benefits of ziritaxestat did not offset its possible risks, and both studies should stop.

Trial investigators are now being informed of the decision, and will be responsible for contacting study participants and telling them to discontinue the treatment.

“We are very disappointed not to be able to bring a novel medication to patients suffering from such a devastating disease with high unmet need. We would like to thank the patients and the medical professionals who participated in the ISABELA studies and contributed to the advancement of IPF research,” Walid Abi-Saab, MD, chief medical officer of Galapagos, said in a press release.

“We intend to learn from this data in our continued commitment to develop therapies in IPF and fibrosis,” Abi-Saab added.

Originally developed by Galapagos, ziritaxestat is an inhibitor of autotaxin, an enzyme that is thought to contribute to IPF progression. In 2019, the company in-licensed ex-European rights to ziritaxestat to Gilead, which was sharing Phase 3 trial costs.

Launched a few months prior to this licensing agreement, the ISABELA program aimed to explore the therapeutic potential of ziritaxestat in up to 1,500 IPF patients, ages 40 and older, diagnosed within five years of enrolling in the studies.

Patients, who were allowed to continue taking their routine medications, were randomly assigned to one of two daily doses (200 or 600 mg tablet) of ziritaxestat, or to a placebo, as an add-on for one year.

The trials’ main goal was to assess whether ziritaxestat might be superior to placebo at slowing lung function decline throughout that year. In both studies, lung function was evaluated by forced vital capacity (FVC), a parameter that measures the total amount of air a person is able to exhale after a deep breath.

“We are extremely disappointed by this news. Despite this setback, we remain committed to leveraging our novel target research engine and strong cash balance to discover potential therapies for IPF and fibrosis,” Onno van de Stolpe, CEO of Galapagos, said.

All other clinical studies of ziritaxestat are also being stopped, including the long-term extension of the Phase 2a NOVESA trial (NCT03976648) in patients with scleroderma.

Detailed data from the ISABELA trials will be presented at future scientific meetings, Galapagos said in its release.