AbbVie, a research-based global biopharmaceutical company, today announced 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 8 weeks, upadacitinib (15/30/45 mg, once daily) met the primary endpoint of clinical remission (per Adapted Mayo Score) and all ranked secondary endpoints. These clinical data, in addition to patient-reported outcomes data from the study, are being presented at United European Gastroenterology (UEG) Week 2018 in Vienna, Austria. Upadacitinib is not approved by regulatory authorities and its safety and efficacy have not been established.
"While 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, M.D., Ph.D., vice president, global immunology development, AbbVie. "These results support the initiation of the Phase 3 clinical trial program to further evaluate upadacitinib in ulcerative colitis, 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 (per Adapted Mayo score) with upadacitinib (14/14/20 percent of patients in the 15/30/45 mg groups) compared to placebo (0 percent) at week 8. Additionally, key secondary endpoints were also achieved at week 8 across the upadacitinib 15/30/45 mg groups, including endoscopic improvement, clinical remission (per Full Mayo Score) and clinical response (per Adapted Mayo Score). The upadacitinib 7.5 mg group did not meet the primary endpoint. These results are being presented today during an oral presentation entitled "Efficacy and safety of upadacitinib as an induction therapy for patients with moderately to severely active ulcerative colitis: data from the phase 2b study U-ACHIEVE" from 2:12 – 2:24 p.m. CEST.
In this study, the safety profile was consistent with that observed in the previously reported Phase 2 Crohn's disease study. No new safety signals were detected. Serious adverse events occurred in 0/4/6/5 percent of the 7.5/15/30/45 mg upadacitinib groups, respectively, compared to 11 percent in the placebo group. Serious infections occurred in 0/2/0/4 percent of the 7.5/15/30/45 mg upadacitinib groups, respectively, compared to 4 percent in the placebo group. One event of herpes zoster with the upadacitinib 45 mg dose and one malignancy (malignant melanoma) with the upadacitinib 7.5 mg dose were reported. No venous thromboembolic events, major adverse cardiovascular events or deaths occurred.
"Ulcerative colitis can be a difficult disease to manage with symptoms that can significantly impact patients' daily lives," said William Sandborn, M.D., study investigator and director, Inflammatory Bowel Disease Center chief, Division of Gastroenterology and Professor of Medicine at the University of California, San Diego and 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. These results further extend our understanding of upadacitinib's potential as an important treatment option for ulcerative colitis patients."
Data from two separate analyses of U-ACHIEVE showing the impact of upadacitinib on patient-reported outcomes were also presented at UEG Week. Results from one analysis showed that patients treated with upadacitinib reported greater improvements in ulcerative colitis symptoms, including bowel urgency, abdominal pain, rectal bleeding and stool frequency, compared to placebo. This presentation, entitled "Induction Therapy of Upadacitinib is Associated with Improved Symptoms in Bowel Urgency and Abdominal Pain for Patients with Ulcerative Colitis: Data from U-ACHIEVE," was featured during the Poster Champ Session on Monday, October 22 from 12:40 – 12:45 p.m. CEST. This session highlights the top 12 poster presentations of the day, selected by the UEG Week Scientific Committee. In another analysis, more patients treated with upadacitinib reported significant and clinically meaningful improvements in disease-specific and general health-related quality of life, fatigue, work productivity and the ability to perform daily activities after 8 weeks of treatment compared to placebo. This poster, entitled "Improved Patient-Reported Outcomes with Upadacitinib as an Induction Therapy for Patients with Ulcerative Colitis: Data from U-ACHIEVE" was presented during the poster session IBD I on Monday, October 22.
Patient-reported outcomes are an important component of understanding how patients perceive the physical, psychological and social burden of their disease. Using patient-reported outcomes data to assess the impact of the disease provides valuable insight to healthcare teams.