AbbVie said Friday that it has produced positive results from U-ACHIEVE, an ongoing Phase 2b/3 dose-ranging study evaluating upadacitinib, an investigational JAK1-selective inhibitor, for induction and maintenance therapy in adult patients with moderately to severely active ulcerative colitis.
After eight weeks, upadacitinib (15/30/45 mg, once daily) met the primary endpoint of clinical remission per Adapted Mayo Score and all ranked secondary endpoints.
The company is currently presenting the data, in addition to patient-reported outcomes data from the study, at United European Gastroenterology (UEG) Week 2018 in Austria.
The company, however, added that upadacitinib has not received approval from regulatory authorities and its safety and efficacy have not been established.
"While the treatment of ulcerative colitis has come a long way, patients are still in need of therapies like upadacitinib that have the potential to provide disease control," said Marek Honczarenko, vice president of AbbVie’s global immunology development department. "These results support the initiation of Phase 3 clinical trial program to evaluate upadacitinib in ulcerative colitis further, underscoring AbbVie's unwavering commitment to the development of treatment options for those living with inflammatory bowel disease."
The study showed that significantly more patients achieved clinical remission with upadacitinib (14, 14,and 20 percent of patients, respectively in the 15, 30 and 45 mg groups) compared to placebo (0 percent) at week 8. Also, the drug achieved key secondary endpoints at week 8 across all upadacitinib 15, 30, and 45 mg groups, including endoscopic improvement, clinical remission and response. The upadacitinib 7.5 mg group did not meet the primary endpoint.
The company also confirmed a consistent safety profile with that observed in the previously reported Phase 2 Crohn's disease study.
Serious adverse events occurred in 0, 4, 6 and 5 percent of the 7.5, 15, 30 and 45 mg upadacitinib groups, respectively, compared to 11 percent in the placebo group, while serious infections occurred in 0, 2, 0 and 4 percent of the 7.5, 15, 30 and 45 mg upadacitinib groups, respectively, compared to 4 percent in the placebo group.
The company also recorded one event of herpes zoster with the upadacitinib 45 mg dose group and one malignancy (malignant melanoma) with the upadacitinib 7.5 mg dose group.
"Ulcerative colitis can be a difficult disease to manage with symptoms that can significantly impact patients' daily lives," said Professor William Sandborn, the lead study investigator. "The U-ACHIEVE study included patients with difficult-to-treat ulcerative colitis, the majority of whom had failed multiple previous therapies, including biologics.”
The research results further extend the possibility of upadacitinib's becoming an important treatment option for ulcerative colitis patients. Sandborn added.