The double-blind, placebo-controlled Phase 2a study, called NOVESA (NCT03798366), will evaluate the efficacy, safety, and pharmacological profile of Galapagos’ GLPG1690. It is set to enroll 30 participants with diffuse cutaneous scleroderma, a condition characterized by skin fibrosis (scarring) in the arms, legs, and trunk, and a higher risk of fibrosis in internal organs such as the lungs.
NOVESA’s primary goal is a change in the modified Rodnan skin score at 24 weeks. This measure assesses skin thickness as a marker of disease severity, with increased thickness linked to involvement of internal organs and higher mortality.
Secondary objectives and exploratory goals include forced vital capacity (FVC) — a measure of lung function — high-resolution computed tomography (most commonly used in lung disease), quality of life as assessed by the Scleroderma Health Assessment Questionnaire, and the Combined Response Index for Systemic Sclerosis, a scleroderma disease composite score.
GLPG1690 is a small molecule that works by selectively inhibiting autotaxin. This enzyme is responsible for the production of the cellular signaling molecule lysophosphatidic acid (LPA), a well-known pro-fibrotic and pro-inflammatory lipid (fat). Prior work revealed that LPA accelerates lung, kidney and liver fibrosis, promotes the release of inflammatory molecules, and reduces apoptosis — “programmed” cell death, as opposed to cell death caused by injury.
Besides scleroderma, Belgium-based Galapagos recently launched the worldwide ISABELA Phase 3 program that will study GLPG1690 in the treatment of idiopathic pulmonary fibrosis (IPF). This program contains two identically designed trials, called ISABELA1 (NCT03711162) and ISABELA2 (NCT03733444).
Results from the Phase 2 FLORA study (NCT02738801) in IPF patients showed that 600 mg of GLPG1690 per day led to an improvement in FVC at 12 weeks, and that treatment with the investigational compound was well-tolerated.
“In addition to our Phase 3 program in IPF, we are excited to broaden our development program with [GLPG1690] to a second indication,” Walid Abi-Saab, Galapagos’ chief medical officer, said in a press release.
“[Scleroderma] is particularly interesting, as this disease straddles our expertise in autoimmune diseases as well as in fibrosis,” Abi-Saab said.
Abi-Saab also highlighted that the anti-inflammatory and anti-fibrotic effects of GLPG1690 mean that it has “the potential to address the important unmet medical need in [scleroderma].”