Celgene Corporation announced that data from a randomized, placebo-controlled, multi-center, phase II clinical trial of apremilast in patients with active ulcerative colitis who had failed at least one conventional therapy but were naïve to biologic therapy were presented in an oral session today at the 13th Congress of ECCO in Vienna (Abstract OP006, 3:30 p.m. CET).
The results showed that a higher proportion of patients taking apremilast 30 mg twice daily (BID) achieved clinical remission versus placebo (nominally significant, P < 0.05). OTEZLA® (apremilast) is Celgene's oral selective inhibitor of phosphodiesterase 4 (PDE4).
In the study, a total of 170 patients were randomized to placebo, apremilast 40 mg BID or apremilast 30 mg BID. The primary endpoint of the study was Total Mayo Score (TMS) clinical remission at week 12 for the 40 mg BID arm. At week 12, TMS clinical remission was achieved by 21.8 percent of patients in the apremilast 40 mg BID arm (n=55) versus 13.8 percent in the placebo group (n=58; P=non-significant (NS)). In the apremilast 30 mg BID arm, 31.6 percent of patients (n=57) achieved clinical remission as measured by TMS at week 12 versus 13.8 percent in the placebo group (n=58; nominally significant, P < 0.05).
"The achievement of clinical remission, which requires endoscopic improvement of the mucosa, is a meaningful goal in the treatment of ulcerative colitis," said presenting author Silvio Danese, M.D., Ph.D., Head of the Inflammatory Bowel Disease Clinical and Research Center, Humanitas Research Hospital. "These findings suggest apremilast, which improved the likelihood of achieving remission in this 12-week study, merits further study in a larger trial."
Clinical remission as measured by Partial Mayo Score (PMS), a secondary endpoint, was achieved by 59.6 percent of patients in the apremilast 30 mg BID arm versus 36.2 percent in the placebo arm (nominally significant, P=0.0124) at week 12. PMS clinical remission was also achieved by 52.7 percent of patients in the apremilast 40 mg BID arm (P=NS versus placebo).
Additional secondary endpoints examined in the trial, including endoscopic remission (Mayo Endoscopic Score ≤1), TMS clinical response, serum biomarkers and mucosal healing (combined endoscopic and histologic remission), showed clinically meaningful improvements for apremilast 30 mg BID versus placebo.
"The strength of these data advances our plans to initiate a phase III program for OTEZLA® (apremilast) 30 mg in ulcerative colitis," said Terrie Curran, President, Celgene Inflammation and Immunology. "We remain committed to bringing forth innovative, oral, immunomodulatory treatment options for patients with inflammatory bowel disease."
Treatment-emergent adverse events reported in at least 5 percent of patients treated with apremilast included headache (23 percent with apremilast 30 mg BID, 26 percent with apremilast 40 mg BID and 7 percent with placebo); viral upper respiratory tract infection (9 percent, 4 percent and 2 percent, respectively); nausea (5 percent, 11 percent and 9 percent); abdominal pain (5 percent, 2 percent and 2 percent); back pain (0 percent, 6 percent and 2 percent); and asthenia (5 percent, 2 percent and 3 percent).
Apremilast is not approved for the treatment of ulcerative colitis in any country. In January 2018, the U.S. Food and Drug Administration designated apremilast an Orphan Drug for the potential treatment of pediatric patients with ulcerative colitis.
About Ulcerative Colitis
Ulcerative colitis is a chronic, relapsing condition triggered by an abnormal, prolonged immune response that creates long-lasting inflammation and ulcers (sores) in the mucosa (lining) of the large intestine (colon). Symptoms usually develop over time, rather than suddenly. The disease can be debilitating and can sometimes lead to life-threatening complications. Ulcerative colitis is the most common form of inflammatory bowel disease worldwide. About one in every 198 people in Europe and one in every 402 people in North America have ulcerative colitis. In 2004, 2.1 million prescriptions were written to treat ulcerative colitis, and 716,000 ambulatory care visits were related to the disease. In 2010, there were 107,000 hospitalizations due to ulcerative colitis.