SAN DIEGO – A new analysis of phase II research finds that the experimental drug ozanimod prompted histologic healing in ulcerative colitis patients at 8 and 32 weeks.
“Ozanimod both induces and maintains remissions in a proportion of patients with refractory ulcerative colitis,” said study coauthor Dr. Stephen B. Hanauer, professor of medicine and medical director of the Digestive Health Center at Northwestern University, Chicago. “It’s a safe and effective oral drug for ulcerative colitis and possibly Crohn’s disease.”
Dr. Stephen B. Hanauer
Ozanimod, an experimental drug developed by Celgene and its subsidiary Receptos, has been undergoing review as a treatment for both multiple sclerosis and ulcerative colitis.
“Ozanimod impacts lymphocyte trafficking by retaining lymphocytes in lymph nodes and prevents recirculation. The mechanism of action is impairing S1P [sphingosine-1-phosphate] that ‘traps’ lymphocytes in lymph nodes.” Dr. Hanauer said.
“Other mechanisms by which lymphocyte trafficking has been inhibited have been effective in treating multiple sclerosis and Crohn’s disease (natalizumab) and both ulcerative colitis and Crohn’s disease (vedolizumab),” he said. However, he said, natalizumab has been linked to a risk of progressive multifocal leukoencephalopathy, a rare and mostly fatal brain disease.
Vedolizumab, meanwhile, “is a biologic that requires IV infusions.” By contrast, he says, ozanimod is an oral drug.
In a recent issue of the New England Journal of Medicine, researchers published findings from a phase II randomized, double-blind, placebo-controlled trial of ozanimod in 197 patients with moderate to severe ulcerative colitis. Patients were assigned to high dose (n = 67), low dose (n = 65), or placebo (n = 65) (N Engl J Med. 2016 May;374:1754-62).
At 8 weeks, clinical remission (Mayo Clinic score less than or equal to 2, with no subscore over 1) occurred in 16% of patients who received 1-mg doses (P = .048) and 14% of those who received the 0.5-mg doses (P = .14); the remission rate was 6% for placebo.
The new analysis examined histologic improvement from baseline to 8 and 32 weeks. (Those who reached clinical response continued through 32 weeks.) Improvement was greater in the high-dose group than in the placebo group at week 8 (Geboes score [–4.37 vs. –2.20; P = .0345]) and week 32 (Geboes score [–5.50 vs. –2.24; P = .0033]); low-dose improvement was greater than placebo but didn’t reach statistical significance.
Histologic remission (Geboes score less than 2) occurred in 15/67 (22.4%) for high dose (P = .0705, compared with placebo), 9/65 (13.8%) for low dose (P = .6294, compared with placebo) and 7/65 (10.8%) for placebo at week 8. At week 32, remission was 21/67 (31.3%) for high dose (P = 0.0006, compared with placebo), 15/65 (23.1%) for low dose (P = .0164, compared with placebo) and 5/65 (7.7%) for placebo.
Adverse events were “minor, without significant cardiotoxicity or risk of infections,” Dr. Hanauer said. The events affected 26/67 (38.8%) patients on the high dose, 26/65 (40.0%) on the low dose, and 26/65 (40.0%) on placebo; worsening of ulcerative colitis and anemia were most common, especially in the placebo group.
The cost of the drug is unclear, Dr. Hanauer said.
The patients are now in open-label follow-up, he said.
The study is industry funded by Receptos. Dr. Hanauer is on the ozanimod steering committee and consults for Celgene and its subsidiary research division, Receptos.