Galapagos NV and Gilead Sciences are discontinuing all clinical trials with the investigational medication ziritaxestat. This includes the long-term extension of the Phase 2a NOVESA trial in scleroderma, as well as the Phase 3 ISABELA program in idiopathic pulmonary fibrosis (IPF).
The decision is based on the recommendations of the ISABELA trials’ Independent Data Monitoring Committee (IDMC), which, after reviewing interim data, concluded the benefit-risk profile of the investigational medication did not support further clinical study. An IDMC is a group of independent experts who periodically review data from an ongoing trial to ensure its integrity and the safety of participants.
The trials’ investigators will be informed of the decision and contact individual participants to discontinue treatment, the companies said.
“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,” Walid Abi-Saab, MD, chief medical officer at Galapagos, said in a press release.
Ziritaxestat (also known as GLPG1690) is a small molecule that blocks the activity of autotaxin. This enzyme produces lysophosphatidic acid, a signaling molecule that promotes fibrosis (scarring) and inflammation in organs. Both scleroderma and IPF are characterized by abnormal scarring.
The clinical trial NOVESA (NCT03798366) recruited 33 adults who have had experienced symptoms of diffuse cutaneous scleroderma for up to five years, or who had new systemic (body-wide) symptoms other than Raynaud’s phenomenon two years prior to recruitment. The study’s main goal was to assess whether ziritaxestat (as oral tablets) helped treat the abnormal skin thickening seen in scleroderma, while also analyzing the therapy’s safety.
The ISABELA program consists of two Phase 3 clinical trials with identical designs, named ISABELA 1 (NCT03711162) and ISABELA 2 (NCT03733444). These studies were designed to test the safety and effectiveness of ziritaxestat in 1,500 people with IPF.
“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. We intend to learn from this data in our continued commitment to develop therapies in IPF and fibrosis,” Abi-Saab said.
“We are extremely disappointed by this news,” added Onno van de Stolpe, CEO of Galapagos. “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.”