brazikumab (AMG 139) / Amgen, AstraZeneca - LARVOL DELTA

Diffusion dimensionality modeling of subcutaneous/intramuscular absorption of antibodies and long-acting injectables. (PubMed, J Pharmacokinet Pharmacodyn) - "The diffusion dimensionality models were challenged with previously published subcutaneous absorption data for 13 antibody drugs and insulin lispro, and the long-acting injectable antipsychotic drugs: subcutaneous Perseris™, intramuscular Invega Sustenna®, Risperdal Consta®, and olanzapine...Three antibodies (CNTO5825, ACE910 and ustekinumab) were best described by the 2-dimensional diffusion equation. The 2- and 3-dimensional diffusion equations were equivalent for ABT981, guselkumab, adalimumab, nemolizumab, omalizumab, and secukinumab. Golimumab, DX2930, AMG139, and mepolizumab were best described by the 3-dimensional diffusion equation. All the long-acting antipsychotic dosage forms except Risperdal Consta were modeled satisfactorily. Diffusion dimensionality models are a parsimonious and effective approach for modeling drug absorption profiles of subcutaneously and intramuscularly administered small molecule and protein drugs and their dosage forms."

Journal • CNS Disorders

EndoUC: an AI-assisted endoscopic Ulcerative Colitis activity grading application for deployment in clinical trials (ECCO-IBD 2025) - P2 | "We used data from the brazikumab clinical trial [NCT03616821], comprising 423 videos from 249 patients scored on the mMS scale...The continuous grading model has an MSE of 0.42 and MAE of 0.40. Conclusion We developed an AI-assisted reading tool for UC endoscopic severity assessment to help accelerate clinical trails through rapid evaluation of patient eligibility, detection of treatment response grounded by key region evidence, and potential for continuous grading of endoscopic changes."

Clinical • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Old and New Biologics and Small Molecules in Inflammatory Bowel Disease: Anti-interleukins (PubMed, Korean J Gastroenterol) - "The review then discusses anti-IL therapies, focusing primarily on ustekinumab (anti-IL-12/23), risankizumab (anti-IL-23), and mirikizumab (anti-IL-23)...The review also briefly discusses emerging therapies such as guselkumab and brazikumab...These agents may be considered first- or second-line therapies for many patients, especially those with comorbidities or safety concerns. Anti-IL therapies represent a significant advancement in IBD treatment, offering effective and relatively safe options for patients with moderate to severe disease."

Journal • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • IL12A • IL23A

Brazikumab: Acceptance of regulatory submission in US/EU/Japan/China for Crohn’s disease in 2022 or later (AstraZeneca) - Annual Report 2020

China filing • EMA filing • FDA filing • Japan filing • Crohn's disease • Immunology • Inflammatory Bowel Disease

Brazikumab: Acceptance of regulatory submission for Crohn’s disease (based on INTREPID trial) post 2024 (AstraZeneca) - Q4 & FY2022 Results

Filing • Crohn's disease • Immunology • Inflammatory Bowel Disease

Post hoc analysis reveals limited efficacy of induction therapy in ileum only Crohn´s disease (ECCO-IBD 2024) - "Results A total of 9 studies, involving 709 adult patients, were identified: two via Embase and PubMed; six from supplementary search materials; and one post-hoc analysis of brazikumab data (not published)...Previous systematic review1 on clinical remission after induction treatment demonstrate placebo adjusted values in the range of 12-20% in a no defined disease site population. This indicates the need for novel therapies with a mechanism of action directly tailored to heal the small intestine in patients with CD."

Clinical • Retrospective data • Crohn's disease • Immunology • Inflammatory Bowel Disease

The Role of IL-23 Inhibitors in Crohn's Disease. (PubMed, J Clin Med) - "With a favorable safety profile, ustekinumab, a monoclonal antibody targeting the shared p40 component of IL-12/23, is currently approved for the treatment of IBD in patients with disease refractory to corticosteroids and biologic drugs. Risankizumab, mirikizumab, and guselkumab are specific IL-23p19 antagonists tested for the treatment of Crohn's disease (CD)...Trials with guselkumab and mirikizumab are currently ongoing, with promising preliminary efficacy and safety results. In this review, we provide a summary of the current knowledge about selective IL-23 inhibitors, focusing on their positioning in the therapeutic algorithm of patients with moderate to severe CD."

Journal • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • IL12A • IL23A

Long-term safety of brazikumab in the open-label period of a randomized phase 2a study of patients with Crohn's disease. (PubMed, BMC Gastroenterol) - P2a | "Brazikumab was well tolerated with an acceptable safety profile over a 100-week period in patients with moderate-to-severe active CD who failed or were intolerant to 1 or more anti-TNFα agents."

Journal • P2a data • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Oncology • Pain

INTREPID: An Active and Placebo-Controlled Study of Brazikumab in Participants With Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P2/3 | N=89 | Terminated | Sponsor: AstraZeneca | Phase classification: P2b ➔ P2/3 | Active, not recruiting ➔ Terminated; Strategic decision to discontinue the development of brazikumab in inflammatory bowel disease.

Phase classification • Trial termination • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

Placebo-Controlled Study of Brazikumab in Participants With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P2 | N=242 | Terminated | Sponsor: AstraZeneca | Active, not recruiting ➔ Terminated; Strategic decision to discontinue the development of brazikumab in inflammatory bowel disease.

Trial termination • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Open-label Extension Study of Brazikumab in Ulcerative Colitis (clinicaltrials.gov) - P2 | N=57 | Terminated | Sponsor: AstraZeneca | Active, not recruiting ➔ Terminated; Strategic decision to discontinue the development of brazikumab in inflammatory bowel disease.

Trial termination • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Risankizumab for the Treatment of Moderate to Severe Crohn’s Disease: A Systematic Review of Literature (ACG 2023) - "Introduction: Anti IL-23 inhibitors (Ustekinumab, Risankizumab, Mirikizumab, Brazikumab, Guselkumab, Tildrakizumab), novel therapeutic targets have been well studied for Psoriasis and Psoriatic arthritis. A total of 5 studies (1 cohort study, 1 phase II randomised control trials(RCTs), 1 phase II open label extension, 2 phase III RCTs) were systematically reviewed in this paper. The following doses of Risankizumab were studied: 200mg, 600mg, 1200mg IV and 180 mg SC. Clinical remission % (defined by CDAI score < 150) was less with 200 mg (15/41 - 37%) in phase 2 trial and was similar for 600mg and 1200mg dosing in the two phase 3 trials (42% vs 40%; 45% vs 42%)."

Review • Crohn's disease • Dermatology • Gastroenterology • Immunology • Inflammatory Arthritis • Inflammatory Bowel Disease • Psoriasis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • IL23A

INTREPID OLE: Open-label Extension Study of Brazikumab in Crohn's Disease (clinicaltrials.gov) - P3 | N=18 | Terminated | Sponsor: AstraZeneca | Active, not recruiting ➔ Terminated; Strategic decision to discontinue the development of brazikumab in inflammatory bowel disease.

Trial termination • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

Combining Pharmacometric Models with Predictive and Prognostic Biomarkers for Precision Therapy in Crohn's Disease: A Case Study of Brazikumab. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "We demonstrated that model derived IB (baseline biomarker levels that achieve 50% of I ) of 22.8 pg/mL and 8.03 mg/L for BIL22 and BCRP as the cutoffs to select subpopulations can effectively identify high-response sub-group patients with improved separation of responders when compared to using the median values as the cutoff. This work exemplifies the utility of pharmacometrics to quantify biomarker-driven responses in biologic therapies and distinguish between predictive and prognostic biomarkers, complementing clinical efforts of identifying subpopulations with higher likelihood of response to brazikumab."

Biomarker • Journal • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease • CRP • IL22

Placebo-Controlled Study of Brazikumab in Participants With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P2 | N=242 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2025 ➔ Oct 2023

Enrollment closed • Trial completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

INTREPID: An Active and Placebo-Controlled Study of Brazikumab in Participants With Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P2b | N=89 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | N=928 ➔ 89 | Trial completion date: Jun 2027 ➔ Oct 2023 | Trial primary completion date: Mar 2027 ➔ Oct 2023

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease • IL22

INTREPID OLE: Open-label Extension Study of Brazikumab in Crohn's Disease (clinicaltrials.gov) - P3 | N=18 | Active, not recruiting | Sponsor: AstraZeneca | Enrolling by invitation ➔ Active, not recruiting | N=161 ➔ 18 | Trial completion date: Apr 2025 ➔ Oct 2023 | Trial primary completion date: Apr 2025 ➔ Oct 2023

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

Open-label Extension Study of Brazikumab in Ulcerative Colitis (clinicaltrials.gov) - P2 | N=58 | Active, not recruiting | Sponsor: AstraZeneca | Enrolling by invitation ➔ Active, not recruiting | N=165 ➔ 58 | Trial completion date: May 2025 ➔ Oct 2023 | Trial primary completion date: May 2025 ➔ Oct 2023

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Update on brazikumab development programme (AstraZeneca Press Release) - "AstraZeneca today announced the discontinuation of the brazikumab inflammatory bowel disease (IBD) development programme, an anti-IL-23 monoclonal antibody, being investigated for the treatment of Crohn’s disease (CD) and ulcerative colitis (UC). The IBD development programme for brazikumab included the Phase IIb/III INTREPID trial in CD and the Phase II EXPEDITION trial in UC, and their respective open-label extension trials. The decision to discontinue brazikumab’s IBD development follows a recent review of brazikumab’s development timeline and the context of a competitive landscape that has continued to evolve. The timeline was impacted by delays that could not be mitigated following global events. No safety concerns were identified for patients in these trials."

Discontinued • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Promising phase II biologics for future Crohn's disease therapy. (PubMed, Expert Opin Investig Drugs) - "Among the most promising biologics are interleukin (IL)-23p19 inhibitors (guselkumab, mirikizumab, and brazikumab), IL-6 inhibitors, and anti-adhesion molecules (ontamalimab). In addition to efficacy, some of them provide reassuring safety profiles. Phase III trials need to confirm these results, especially on their long-term safety issues."

Journal • P2 data • Review • Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

THE COMPARISON OF THE EFFICACY OF INTERLEUKIN (IL)-23 TARGETED DRUGS IN THE TREATMENT OF CROHN’S DISEASE: A BAYESIAN NETWORK META-ANALYSIS (EULAR 2023) - "According to SUCRA, Ustekinumab (79.3%), Risankizumab (53.7%), PBO(22.1%), Mirikizumab(33.4%), Guselkumab (90.3%)and Brazikumab (21.7%) . Conclusion In terms of efficacy alone, Guselkumab ranked first among all IL-23 inhibitors, followed by Ustekinumab, and all had significantly different clinical remission rates than patients in the PBO group, while the remaining drugs were less effective than PBO."

Retrospective data • CNS Disorders • Crohn's disease • Gastroenterology • Immunology • Inflammation • Inflammatory Bowel Disease • CRP • IL17A • IL23A

Brazikumab: Data from P2 EXPEDITION trial (NCT03616821) for ulcerative colitis post 2024 (AstraZeneca) - Q1 2023 Results

P2 data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

IL-12 and IL-23 pathway inhibition in inflammatory bowel disease. (PubMed, Nat Rev Gastroenterol Hepatol) - "An increased understanding of these biological effects, particularly the pro-inflammatory effects mediated by IL-12 and IL-23, has led to the development of monoclonal antibodies that target a subunit common to IL-12 and IL-23 (p40; targeted by ustekinumab and briakinumab), or the IL-23-specific subunit (p19; targeted by risankizumab, guselkumab, brazikumab and mirikizumab). This Review provides a summary of the biology of the IL-12 family cytokines IL-12 and IL-23, discusses the role of these cytokines in intestinal homeostasis and inflammation, and highlights IL-12- and IL-23-directed drug development for the treatment of Crohn's disease and ulcerative colitis."

Journal • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • IL12A • IL23A

Placebo-Controlled Study of Brazikumab in Participants With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P2 | N=256 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Apr 2024 ➔ Jan 2025 | Trial primary completion date: Feb 2023 ➔ Nov 2023

Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Brazikumab: Data from P2 trial (NCT04277546) for ulcerative colitis post 2024 (AstraZeneca) - Q4 & FY2022 Results: Data from P1 trial (NCT05033431) in healthy volunteers in H1 2023

P1 data • P2 data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis