Galapagos Reports Positive Topline Results in Phase 2 Sclerosis Trial

Rare Daily Staff

Galapagos reported positive topline results in the NOVESA phase 2a clinical trial of its experimental therapy ziritaxestat in patients with diffuse cutaneous systemic sclerosis.

Diffuse cutaneous systemic sclerosis (dcSSc) is a severe autoimmune disease with one of the highest mortality rates among rheumatic diseases, and no drugs currently approved to treat the overall disease. Systemic sclerosis (SSc) affects approximately 124,000 people in the US and Europe, with a predominance of female patients (greater than 80 percent). It causes hardening of the skin and problems in many organs. The condition can include a wide range of symptoms including joint pain, muscle pain, weakness, and cramps. More serious cases involve lung and kidney problems.

Ziritaxestat is a small molecule, selective autotaxin inhibitor co-developed with Gilead Sciences as part of the global collaboration between the two companies. Autotaxin is the main enzyme responsible for lysophosphatidic acid (LPA) production. LPA is a well-known pro-fibrotic and pro-inflammatory lipid. Ziritaxestat has Orphan Drug designation from regulators in the United States and European Union in both idiopathic pulmonary fibrosis (IPF) and SSc and is currently being studied in a global phase 3 program in IPF in addition to the ongoing NOVESA extension trial.  

NOVESA is a double-blind, placebo-controlled phase 2a proof-of-concept trial evaluating the efficacy, safety and tolerability of ziritaxestat (GLPG1690) in 33 patients with dcSSc. Patients recruited for NOVESA included mostly females (70 percent) around 50 years old, with a mean disease duration of 1.9 years. Most patients enrolled were on a background immunosuppressant therapy during the study.

Ziritaxestat reached the primary endpoint of the NOVESA study with a statistically significant change from baseline in the modified Rodnan Skin Score at Week 24, of -8.3 vs -5.7 for placebo. 

Ziritaxestat was generally well tolerated. No deaths were reported in this study. Two patients taking ziritaxestat experienced serious adverse events versus one patient in the placebo group. Both patients in the ziritaxestat group recovered fully and are still participating in the long-term extension trial. Thirty one of the 33 participants who completed the NOVESA trial continued in the long-term open label extension trial.

“After showing promising activity in the phase 2 FLORA trial in idiopathic pulmonary fibrosis, ziritaxestat achieved statistically significant improvements in mRSS in diffuse SSc, the primary endpoint in the NOVESA study,” said Walid Abi-Saab, chief medical officer of Galapagos. “We will now further analyze the NOVESA data to determine next steps in SSc, a disease with important unmet medical need.”

Photo: Walid Abi-Saab, chief medical officer of Galapagos