Second Phase 3 Induction Study Confirms Upadacitinib (RINVOQ®) Achieves Clinical Remission and Endoscopic Response in Crohn’s Disease

Crohn's Disease (CD)

News on February 25, 2022 /BioValleyBIOON/ -- AbbVie recently announced the novel anti-inflammatory drug, oral JAK1 inhibitor Rinvoq (Rui Fu®, Generic name: upadacitinib, Upadacitinib Extended-Release Tablets) for the treatment of moderate to severe Crohn's disease (CD) in the Phase 3 induction study U-EXCEL (NCT03345849). This study is the second of two Phase 3 induction studies, enrolling adult patients with moderate to severe CD who have had an inadequate response or intolerance to one or more conventional and/or biologic therapies.

In December 2021, AbbVie announced positive topline results from the Phase 3 induction study U-EXCEED (NCT03345836). This study is the first of two Phase 3 induction studies, enrolling adult patients with moderate to severe CD who had an inadequate response or were intolerant to biologics, with more than 60% of the patients having previously received treatment with two or more biologics. (For details, see:New Drug for Crohn's Disease (CD)! AbbVie's Oral JAK1 Inhibitor Rinvoq First Phase 3 Induction Study Successful: Achieves Clinical Remission & Endoscopic Response Endpoint!）

U-EXCEL has the same primary endpoint and key secondary endpoints as U-EXCEED.Results from 2 studies showed that at Week 12 of treatment, Rinvoq (45mg, once daily) achieved the primary endpoints of clinical remission and endoscopic response.

Clinical remission was measured by the Crohn's Disease Activity Index (CDAI) and patient-reported stool frequency/abdominal pain symptoms (SF/AP). Data from the U-EXCEL study showed that, compared with placebo, a significantly higher proportion of patients receiving 12 weeks of Rinvoq induction therapy (45mg, once daily) achieved CDAI clinical remission at week 12 (49% vs 29%; p<0.0001). The clinical remission rate evaluated by SF/AP also demonstrated similar results (51% vs 22%; p<0.0001). In the study, all patients were also assessed for mucosal healing via endoscopy. At week 12, a higher proportion of patients in the Rinvoq (45mg, once daily) group achieved endoscopic response compared to the placebo group (46% vs 13%; p<0.0001).

Results of Two Induction Studies (U-EXCEL, U-EXCEED)

Consistent with the results of the U-EXCEED induction study, data from the U-EXCEL study showed that, among patients receiving corticosteroids at baseline, a significantly higher proportion of patients in the Rinvoq (45mg, once daily) treatment group achieved steroid-free clinical remission at week 12 compared to the placebo group (assessed by CDAI and SF/AP). Additionally, compared to the placebo group, a significantly higher proportion of patients in the Rinvoq treatment group achieved early symptom improvement at week 2 (assessed by CR-100, defined as a reduction of ≥100 points in CDAI score from baseline) and clinical remission at week 4.

During the 12-week, double-blind, placebo-controlled period, the safety of Rinvoq 45mg was consistent with the safety profile observed in previous studies for the indicated conditions, with no new safety risks identified. The most common adverse events in the Rinvoq treatment group were acne andAnemiaIn the study, one adjudicated major adverse cardiovascular event (MACE) was reported in the placebo group. No adjudicated MACE or malignancies were reported in the Rinvoq treatment group.Tumor, Venous thromboembolic events.

The full results of the U-EXCEL study will be presented at an upcoming medical conference.MeetingPublished online. Dr. Michael Severino, Vice Chairman and President of AbbVie, stated, "The results of this study reaffirm the data from the U-EXCEED study and demonstrate the potential impact Rinvoq may have on clinical and endoscopic outcomes in patients with moderate to severe Crohn's disease. Our decades-long collaboration with the gastroenterology community underscores AbbVie’s commitment to discovering and developing multiple treatment options for patients with inflammatory bowel disease.”

Crohn's Disease (CD) is a chronic systemic disease characterized by inflammation within the gastrointestinal (or digestive) tract, causing persistent diarrhea, abdominal pain, and rectal bleeding. It is a progressive disease, meaning that the condition worsens over time. Because the signs and symptoms of CD are unpredictable, it imposes a tremendous burden on patients not only physically but also emotionally and financially.

The active pharmaceutical ingredient in Rinvoq is upadacitinib, an orally administered, selective, and reversible JAK1 inhibitor discovered and developed by AbbVie. It is being developed for the treatment of several immune-mediated inflammatory diseases. JAK1 is a kinase that plays a critical role in the pathophysiological processes of various inflammatory diseases.

As of now, Rinvoq has been approved for 4 indications in the EU (Rheumatoid Arthritis[RA], psoriatic arthritis [PsA], ankylosing spondylitis [AS], atopic dermatitis [AD]), in the United States, three indications have been approved (RA, PsA, AD). Rinvoq 15mg dosage is suitable for treating all of the above indications, while Rinvoq 30mg is only suitable for treating AD.

Notably, Rinvoq (瑞福®Upadacitinib Sustained-Release Tablets) is the first oral selective JAK inhibitor approved in China for the treatment of atopic dermatitis, ushering in a new era of oral targeted treatment for atopic dermatitis in China. Globally synchronized, it brings a new treatment option to Chinese patients. In August 2021 and January 2022, Rinvoq was approved for the indication of atopic dermatitis in the EU and the US, respectively. (Bioon.com)

Source of the original text:Second Phase 3 Induction Study Confirms Upadacitinib (RINVOQ?) Improved Clinical and Endoscopic Outcomes in Patients with Crohn's Disease