Results from the first trial testing the oral autotaxin inhibitor ziritaxestat in adults with diffuse cutaneous systemic sclerosis have encouraged its originator, Galapagos NV, to explore next steps for the program, it said on Sept. 11. Need in the indication is high, with no drugs currently approved to treat the overall disease. The news appeared to expand the potential applications of the candidate, a key element in the company's decade-long alliance with Gilead Sciences Inc., that is also in development for idiopathic pulmonary fibrosis.
RBC Capital Markets analyst Brian Abrahams called news from the trial "modestly positive" for Galapagos shares, which he said "may have overshot to the downside" following the FDA's recent rejection of the company's Gilead-partnered multiple sclerosis drug, filgotinib.
Systemic sclerosis affects about 124,000 people in the U.S. and Europe, most of them female.
During the course of the phase IIa SSc trial, called Novesa, the skin thickening that characterizes the disease was reduced by a mean 8.3 points in patients randomized to ziritaxestat vs. 5.7 points for those in the placebo arm (p=0.0411). Both measures reflected statistically significant improvements from baseline, as measured using the modified Rodnan Skin Score (mRSS), a common assessment used in systemic sclerosis trials. The drug was generally well-tolerated, too, Galapagos said.
"Skin thickness – measured by mRSS – tends to increase early in disease and decrease later in disease, and an increase in thickening is associated with worsening internal organ involvement and increased mortality," said RBC’s Abrahams. "Our prior physician feedback had indicated a 4-5-[point] mRSS difference would be viewed as clinically meaningful, so the 2.6-[point] delta appears to be on the more modest end, though it is a high unmet need disease," he said.
Galapagos' chief medical officer, Walid Abi-Saab, said he was pleased with the results and that his team was "excited to see that after showing promising activity in the phase II Flora trial in idiopathic pulmonary fibrosis, ziritaxestat achieved statistically significant improvements in mRSS in diffuse SSc," the primary endpoint in the study. He committed to further analysis of the trial data to determine next steps, too.
The enthusiasm appeared to be tempered, however, by the fact that most patients enrolled in the study were on background immunosuppressant therapy, making it "difficult to measure" the impact on skin, he said. The company did not respond to a request for further information on Friday.
A clear example of the challenge Galapagos may face in measuring the impact of its drug arrived in a negative phase III trial of the Corbus Pharmaceuticals Holdings Inc. candidate lenabasum just earlier this week. In that trial, Corbus enrolled 365 patients with diffuse SSc. The company chalked up its outcome, a failure to separate from placebo on another measure of sclerosis, to a high-profile issue: "Unprecedented improvement" in subjects on placebo added to background drug therapy.
"Immunosuppressive drugs, alone or in combination, are increasingly becoming a mainstay of treatment for patients with early diffuse cutaneous SSc," said Robert Spiera, co-principal investigator on the Corbus study. "However, the impact of these drugs on disease has not previously been studied systematically and clearly was underappreciated by the community of SSc experts."
Two patients taking ziritaxestat in Galapagos' study experienced serious adverse events vs. just one patient in the placebo group. Both patients in the ziritaxestat group recovered fully, Galapagos said, and are still participating in a long-term extension trial.
Galapagos' U.S.-listed shares (NASDAQ:GLPG) climbed 8.8% to $136.85 on Friday following a similar increase in the company's Euronext Belgium shares.