The results could help with the large unmet need for more GCA treatment options, Dr. Cid said.
Ziritaxestat
A phase 2a trial called NOVESA with 33 patients who have active diffuse cutaneous systemic sclerosis (dcSSc) found the autotaxin inhibitor ziritaxestat (GLPG1690) significantly improved their Rodnan skin score compared with placebo at week 24, said Dinesh Khanna, MD, director of the Scleroderma Program at the University of Michigan, Ann Arbor.
Per standard of care, 95.2% of ziritaxestat patients and 83.3% of placebo patients used background immunosuppressive therapy.4 Patients were randomized 2:1 for oral ziritaxestat 600 mg daily or matching placebo for 24 weeks. Patients were adults with a confirmed dcSSc diagnosis and a modified Rodnan skin score of more than 10 at screening. A statistically significant difference (least square mean difference, –2.8) in the mean Rodnan skin score was observed between the treatment versus placebo groups.
Two serious adverse events occurred in the ziritaxestat group and one in the placebo group, but they were likely not linked to the study drug.
Thirty-one of the 33 patients opted to continue in an open-label extension study to continue ziritaxestat for the next 48 months, Dr. Khanna said.
VIB7734, a Monoclonal Antibody
A phase 1 study with the monoclonal antibody VIG7734, which selectively targets plasmacytoid dendritic cells (pDCs), led to reduced blood and skin pDCs and a subsequent reduction in type 1 interferon levels in blood and inflamed skin among subjects with lupus, reported Victoria Werth, MD, professor of dermatology at the Hospital of the University of Pennsylvania, Philadelphia.
The randomized, double-blind, placebo-controlled, multiple ascending dose trial enrolled adult subjects in three sequential cohorts and a placebo group.5 Cohort 1 (n=6) included patients with systemic lupus erythematosus (SLE) or Sjögren’s syndrome; cohorts 2 and 3 (n=16 overall) included subjects with SLE or cutaneous lupus erythematosus with a CLE Disease Area and Severity Index Activity score of 8 or greater. The placebo group included nine subjects.
Subjects received treatment or placebo subcutaneously every four weeks, as well as three doses as an add-on. Levels of pDC were quantified in the blood and skin, and a type 1 interferon signature was measured.
At week 1, a decrease in circulating pDCs was seen, which continued through the three months of treatment. The median change in interferon 1 signature at three months was –54% in the VIB7734 50 mg group, –83% in the 150 mg group and +8% in the placebo group. Safety was similar among the treatment and placebo groups, Dr. Werth said.
