Ozespa (briakinumab) / AbbVie - LARVOL DELTA

Prioritizing drug targets in systemic lupus erythematosus from a genetic perspective: a druggable genome-wide Mendelian randomization study. (PubMed, Clin Rheumatol) - "This study identified five genes as therapeutic targets for SLE. Repurposing and developing drugs targeting these genes is anticipated to improve the existing treatment state for SLE. Key Points • We identified five gene targets of priority for the treatment of SLE, with BLK and IL12A indicating fewer side effects. • Among the existing drugs that target these candidate genes, Ustekinumab, Ebdarokimab, and Briakinumab (targeting the IL12 gene) and CD24FC (targeting HSPA1A) may potentially be repurposed for the treatment of SLE."

Journal • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • BLK • HSPA1A • IL12A • NEU1

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

INTERLEUKIN-23 AND INTERLEUKIN-12/23 INHIBITORS FOR THE TREATMENT OF CROHN’S DISEASE: SYSTEMATIC REVIEW AND META-ANALYSIS (UEGW 2022) - "Ten studies assessed IL-12/23 inhibitors (ustekinumab [UST], briakinumab [BRI], and apilimod mesylate [AM]) and eight studies assessed IL-23 inhibitors (brazikumab [BRA], risankizumab [RIS], guselkumab [GUS], and mirikizumab [MIR]). All studies except two were placebo-controlled; in these studies, two active agents (UST vs. adalimumab) and two doses of the same agent (UST) were evaluated, respectively... Drugs targeting IL-23 are effective for inducing and maintaining clinical remission in patients with moderate-to-severe CD."

Retrospective data • Review • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease • Pediatrics • IL12A • IL23A

Adverse Effects of Anti-Interleukin-23 Agents Employed in Patients with Psoriasis: A Systematic Review. (PubMed, Dermatology) - "Targeted IL-23 therapy has expeditiously upsurged to the forefront as the importance of the IL-23 axis has been progressively identified, setting a new benchmark for psoriasis outcomes. Over the last 3 years, ustekinumab, guselkumab, tildrakizumab, and risankizumab have successively come to the market. However, these drugs caused several immunological and nonimmunological side effects, but they are customarily well-tolerated and have orderly safety vignettes."

Adverse events • Journal • Review • Back Pain • Dermatology • Immunology • Infectious Disease • Musculoskeletal Pain • Pain • Psoriasis • Respiratory Diseases • IL23A

Cardiovascular Safety of Biologics Targeting Interleukin (IL)-12 and/or IL-23: What Does the Evidence Say? (PubMed, Am J Clin Dermatol) - "We performed a literature search for currently known CV safety data from trials and observational studies of treatments targeting IL-12/23 in psoriasis, i.e. the p40 inhibitors ustekinumab and briakinumab, and the p19 inhibitors guselkumab, risankizumab, and tildrakizumab. The safety evidence from RCTs on the p19 inhibitors are reassuring thus far, but these studies may not detect rare CV events in real-world patients. We concluded that the overall evidence does not show that ustekinumab is associated with an increase in the risk of CV disease in patients with psoriasis, but further data are awaited to assess the CV safety of p19 inhibitors for the treatment of psoriasis."

Clinical • Journal • Atherosclerosis • Cardiovascular • Dermatology • Immunology • Psoriasis • IL12A

Open Label, Single Dose, Non-randomized Study to Assess the Drug to Drug Interaction of Briakinumab on CYP Substrates. (clinicaltrials.gov) - P1; N=12; Withdrawn; Sponsor: Abbott; Terminated ➔ Withdrawn

Clinical • Trial withdrawal • Dermatology • Immunology • Psoriasis • CYP1A2 • CYP2C19 • CYP2C9 • CYP3A4

[VIRTUAL] GENOME-WIDE META-ANALYSIS OF PRIMARY BILIARY CHOLANGITIS IDENTIFIES 21 ADDITIONAL RISK LOCI AND PRIORITISES DRUG CANDIDATES POTENTIALLY SUITABLE FOR RE-PURPOSING (AASLD 2020) - "This study provides a hierarchy of agents that could be trialled in PBC, and emphasises the value of genetic and genomic approaches to drug discovery in complex disorders."

Retrospective data • CNS Disorders • Crohn's disease • Dermatology • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Idiopathic Arthritis • Immunology • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Multiple Sclerosis • Primary Biliary Cholangitis • Psoriasis • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CTLA4 • IL12A

Emerging Treatment Options in Inflammatory Bowel Disease: Janus Kinases, Stem Cells, and More. (PubMed, Digestion) - "Two pharmacological principles have been successfully used for IBD treatment: inhibition of cellular signaling and interference with leukocyte trafficking. Besides tumor necrosis factor, interleukin (IL)-23 is a promising drug target, and antibodies for the combined inhibition of IL-23 and IL-12 (ustekinumab and briakinumab) or selective IL-23 inhibition (brazikumab, risankizumab, and mirikizumab) seem to be effective in Crohn's disease (CD) with emerging evidence also for ulcerative colitis (UC). Janus kinase (JAK) mediates intracellular signaling of a large number of cytokines. Tofacitinib is the first JAK inhibitor approved for UC, and the JAK inhibitors filgotinib and upadacitinib showed potential in CD. Leukocyte trafficking can be inhibited by interference with lymphocyte integrin-α4β7 or endothelial MadCAM-1. The α4β7 integrin inhibitor vedolizumab is an established treatment in IBD, and long-term data of pivotal studies are now available. Additional molecules..."

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

Psoriasis patients on TNF-alpha blockers not at risk for cardiovascular disease (Clinicaladvisor) - P=NA, N=10,183; "During the placebo-controlled phases of the anti-IL-12/23 studies, 10 of the 3,179 patients treated with these therapies had a major adverse cardiac event compared with zero events in the 1,474 patients treated with placebo. In studies of patients taking anti-TNF-alpha agents, one of the 3,858 patients had a major adverse cardiac event compared with one of the 1,812 treated with placebo."

Retrospective data • Biosimilar • Immunology • Psoriasis

Anti-IL-12/23p40 antibodies for maintenance of remission in Crohn's disease. (PubMed, Cochrane Database Syst Rev) - "Moderate-certainty evidence suggests that ustekinumab is probably effective for the maintenance of clinical remission and response in people with moderate to severe CD in remission without an increased risk of adverse events (high-certainty evidence) or serious adverse events (moderate-certainty evidence) relative to placebo. The effect of briakinumab on maintenance of clinical remission and response in people with moderate to severe Crohn's disease in remission was uncertain as the certainty of the evidence was low. The effect of briakinumab on adverse events and serious adverse events was also uncertain due to low-certainty evidence. Further studies are required to determine the long-term efficacy and safety of subcutaneous ustekinumab maintenance therapy in Crohn's disease and whether it should be used by itself or in combination with other agents. Future research comparing ustekinumab with other biologic medications will help to determine when treatment with..."

Clinical • Journal • Review • Basal Cell Carcinoma • Cardiovascular • Crohn's disease • Gastroenterology • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Bowel Disease • Oncology • Pain • Respiratory Diseases • Thrombosis • Venous Thromboembolism

Abbott withdraws applications for psoriasis drug (Reuters) -

Abbott withdrew its U.S. & European applications for briakinumab after regulators indicated the need for more analysis & potential further studies; Company plans to evaluate its next steps for including resubmission at a later date;

Regulatory • Immunology

Biologics Up Cardiovascular Risk, New Analysis Finds (Skin and Allergy News Digital Network) -

One pt on PBO developed a major cardiovascular event in a study of etanercept; Five pts on ustekinumab, five on briakinumab, & one on adalimumab developed major cardiovascular events;

Immunology

Short- and long-term briakinumab efficacy in moderate to severe psoriasis patients with prior TNF antagonist exposure: Subanalysis of a 52-week phase III trial and open-label extension (AAD 2012) - P3, N=252; High percentage of briakinumab-treated pts achieved PASI 75 & a PGA of 0 or 1 at Weeks 8 and 52; This level of response was maintained through OLE Week 48; Serious adverse event rates were low & similar across groups

P3 data • Immunology • Psoriasis

Cardiovascular risk and psoriasis: The role of biologic therapy (Actas Dermosifiliogr) - Pubmed ID: 23157913; "...a numerical imbalance (without statistical significance) between the groups receiving the biologic drug and the placebo groups was recently observed in the incidence of major cardiovascular events (nonfatal myocardial infarction and cerebrovascular accident and cardiovascular death) during the controlled periods of clinical trials of briakinumab and ustekinumab..."

Review • Immunology • Psoriasis

Briakinumab tops methotrexate for psoriasis in phase III study (Skin and allergy news) - P3, N=317; NCT00679731; Briakinumab was more effective than methotrexate at reducing the signs and symptoms of moderate to severe plaque psoriasis in a 52-week, phase-III study reported in the Oct. 27 issue of the New England Journal of Medicine; Significantly more pts in briakinumab group showed at least 75% improvement in their score on psoriasis area & severity index (PASI) at both week 24 (81.8%) & week 52 (66.2%), compared with patients on methotrexate (39.9% at week 24 and 23.9% at week 52)

P3 data • Immunology • Psoriasis

Interim results from an open-label extension study of briakinumab for the treatment of moderate to severe psoriasis (AAD 2012) - P3, N=2,520; NCT00626002; 20 major adverse cardiovascular events (MACE) were observed during open-label extension study (OLE), in addition to 7 from one run-in study (27 total events; 19 nonfatal MIs, 3 non-fatal strokes, & 5 cardiovascular deaths); Interim results support need for continued close monitoring of rates of infection & NMSC & cardiovascular risk factors that may contribute to MACE in pts receiving briakinumab for treatment of moderate to severe psoriasis

Interim report • P3 data • Immunology • Psoriasis

Dose ranging study comparing the efficacy, safety and pharmacokinetics of intravenous infusions of ABT-874 vs placebo in subjects with active Crohn's disease -

P2, N=246

Comparative efficacy and safety of thirteen biologic therapies for patients with moderate or severe psoriasis: A network meta-analysis. (PubMed, J Pharmacol Sci) - "Briakinumab performed relatively stable under efficacy and safety outcome. Infliximab can be a good choice for its lower risk of infection. Brodalumab present very good potential in efficacy outcome like PASI and PGA. More clinical trials are required to supply more data about discontinuation of infliximab and infection of brodalumab and larger RCT for assessment of briakinumab."

Journal • Retrospective data

Briakinumab versus Metotrexate for Psoriasis - "Dr. Wu reports on receiving research funds from Abbott Laboratories, Amgen and Pfizer that were not directly related to this letter."

Brodalumab in Patients With or Without Previous Use of Biologic Agents: Long-term Findings From Two Phase 3 Psoriasis Studies (AAD 2019) - "...Efficacy and safety of brodalumab in pts with or without previous use of biologic agents was analyzed using data from long-term extension studies of 2 randomized, double-blind clinical trials (AMAGINE-2/-3).2 Pts with moderate-to-severe psoriasis were initially randomized to brodalumab 140 or 210 mg every 2 wk, ustekinumab, or placebo... Among 3625 pts in the efficacy analysis, 963 were biologic experienced at baseline, with therapies including anti–tumor necrosis factor biologics, briakinumab, or efalizumab, and 2662 pts were biologic naive... Skin clearance efficacy was observed through 120 wk among both biologic-experienced as well as biologic-naive pts who received brodalumab. Brodalumab can be efficacious and well tolerated in pts with moderate-to-severe psoriasis and prior exposure to biologics."

Clinical • P3 data