A Phase 2 trial (NCT02365649) of AbbVie’s investigational compound upadacitinib (ABT-494) showed the treatment had a positive effect in patients with Crohn’s disease, supporting the drug’s advance to Phase 3 trials.
Data from the trial, called CELEST, was presented at the Digestive Disease Week 2017 conference May 6-9 in Chicago.
The study had particularly focused on patients who had failed previous treatments with immunomodulating drugs or TNF inhibitors, and all patients had moderately to severely active disease.
Researchers recruited 220 patients, who were randomized to receive placebo or one of five upadacitinib dose regimens for 16 weeks. The doses investigated were 3, 6, 12, or 24 mg twice daily, or 24 mg once a day. After 16 weeks, an extension phase of 36 weeks followed.
Of these, 180 patients completed the study. Endoscopic remission — measured by the Simplified Endoscopic Score for Crohn’s Disease scale — was more common in upadacitinib-treated patients. In the 24 mg twice daily treatment group, 22 percent achieved endoscopic remission, compared to none in the placebo group.
Endoscopic remission, along with clinical remission, was the trial’s primary outcome measure. Clinical remission was also more common after upadacitinib treatment — with 27 percent in the 6 mg dose group achieving it, compared to 11 percent in the placebo group.
“Crohn’s disease is a serious, chronic disease with symptoms and complications that can have a major impact on patients’ daily lives, and additional treatments are needed to improve the prognosis for many living with the disease,” William Sandborn, MD, study investigator and director, Inflammatory Bowel Disease Center at the University of California, San Diego (UCSD), said in a press release.
“The CELEST study included patients with difficult-to-treat Crohn’s disease who failed two or more biologics. These positive results support advancement into Phase 3 to further explore a potential new treatment option that may address the unmet needs of patients living with this challenging disease,” said Sandborn, who is also chief of the Division of Gastroenterology and a professor of medicine at UCSD.
The safety profile of the drug was in line with what researchers had seen in Phase 3 trials of upadacitinib in patients with rheumatoid arthritis. Adverse events were more common in patients treated with upadacitinib than placebo, but researchers reported that they did not seem to be dose-related.
Severe adverse events were similar in the various groups, except for the 12 mg upadacitinib, where severe events were numerically more common. The numbers of patients who stopped the treatment early were also similar across the dose groups.
Patients who completed the Phase 2 trial could enter a long-term, open-label extension trial (NCT02782663), in which all patients receive the drug.
“Results from CELEST are encouraging and provide new information to the gastroenterology community on the potential for upadacitinib as an oral treatment option for patients with Crohn’s disease,” said Michael Severino, MD, executive vice president, research and development, and chief scientific officer of AbbVie.
Upadacitinib is an oral treatment that targets a molecule known as JAK1, which researchers think plays a role in Crohn’s disease. In addition to Crohn’s, the drug is also explored for ulcerative colitis and atopic dermatitis, and Phase 3 trials in rheumatoid arthritis and psoriatic arthritis are underway.
“For nearly two decades, AbbVie has pioneered research in immune-mediated diseases, and these findings demonstrate our commitment to meaningful scientific innovation with the potential to improve patient lives,” Severino said.