remtolumab (ABT-122) / AbbVie - LARVOL DELTA

Dual Immunomodulatory Therapies in Psoriatic Disease (EULAR 2022) - "Multiple pathways and mediators are responsible for the initiation of and sustained joint inflammation and damage seen in PsA. A phase II trial of ABT-122, a biologic engineered to target both TNF and IL-17A showed statistically significant superior efficacy outcomes at multiple time points based on ACR50, ACR70 and psoriasis outcome measures (PASI75/PASI90) when compared to adalimumab, with similar safety profile.(2) Safety concerns such as infectious risks are important considerations with such strategies; however, the targeted second-generation anti-cytokine biologics and targeted JAK-I have exhibited improved safety profiles.(3) In our small case series, patients have not, to date, experienced adverse events of combination therapy."

Dermatology • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Musculoskeletal Diseases • Orthopedics • Psoriasis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • IL17A • IL23A

Efficacy of pharmacological treatment in rheumatoid arthritis: a systematic literature research informing the 2019 update of the EULAR recommendations for management of rheumatoid arthritis. (PubMed, Ann Rheum Dis) - "This SLR informed the task force regarding the evidence base of various therapeutic regimen for the development of the update of EULAR's RA management recommendation."

Clinical • Journal • Immunology • Rheumatoid Arthritis • Rheumatology

A Phase 2 Study to Investigate the Safety, Tolerability and Efficacy of ABT-122 in Subjects With Active Psoriatic Arthritis (PsA) Who Have an Inadequate Response to Methotrexate (MTX) (clinicaltrials.gov) - P2; N=220; Recruiting; Sponsor: AbbVie; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • P2 data • Immunology • Inflammation • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CRP

A Phase 2 Study to Investigate the Safety, Tolerability and Efficacy of ABT-122 in Subjects With Active Psoriatic Arthritis (PsA) Who Have an Inadequate Response to Methotrexate (MTX) (clinicaltrials.gov) - P2; N=220; Recruiting; Sponsor: AbbVie; Initiation date: Apr 2015 ➔ Jan 2015

Clinical • P2 data • Trial initiation date • Immunology • Inflammation • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CRP

A Phase 2 Study to Investigate the Safety, Tolerability and Efficacy of ABT-122 in Subjects With Active Psoriatic Arthritis (PsA) Who Have an Inadequate Response to Methotrexate (MTX) (clinicaltrials.gov) - P2; N=231; Completed; Sponsor: AbbVie; Active, not recruiting ➔ Completed

Clinical • P2 data • Trial completion • Immunology • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CRP

A Phase 2 Study to Investigate the Safety, Tolerability and Efficacy of ABT-122 in Subjects With Active Psoriatic Arthritis (PsA) Who Have an Inadequate Response to Methotrexate (MTX) (clinicaltrials.gov) - P2; N=220; Active, not recruiting; Sponsor: AbbVie; Recruiting ➔ Active, not recruiting; Initiation date: Jan 2015 ➔ Apr 2015

Clinical • Enrollment closed • P2 data • Trial initiation date • Immunology • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CRP

A Phase 2 Study to Investigate the Safety, Tolerability and Efficacy of ABT-122 in Subjects With Active Psoriatic Arthritis (PsA) Who Have an Inadequate Response to Methotrexate (MTX) (clinicaltrials.gov) - P2; N=220; Not yet recruiting; Sponsor: AbbVie

Clinical • New P2 trial • P2 data • Immunology • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CRP

A Phase 2, Multicenter Open-Label Extension (OLE) Study With ABT-122 in Active Psoriatic Arthritis Subjects Who Have Completed a Preceding Study M14-197 (clinicaltrials.gov) - P2; N=168; Terminated; Sponsor: AbbVie; Active, not recruiting ➔ Terminated; Trial primary completion date: Nov 2016 ➔ May 2016; Internal business decision

Clinical • P2 data • Trial primary completion date • Trial termination • Immunology • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CRP

A Phase 2, Multicenter Open-Label Extension (OLE) Study With ABT-122 in Active Psoriatic Arthritis Subjects Who Have Completed a Preceding Study M14-197 (clinicaltrials.gov) - P2; N=110; Enrolling by invitation; Sponsor: AbbVie; Not yet recruiting ➔ Enrolling by invitation; Initiation date: Jun 2015 ➔ Sep 2015

Clinical • Enrollment open • P2 data • Trial initiation date • Immunology • Inflammation • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CRP

A Phase 2, Multicenter Open-Label Extension (OLE) Study With ABT-122 in Active Psoriatic Arthritis Subjects Who Have Completed a Preceding Study M14-197 (clinicaltrials.gov) - P2; N=200; Enrolling by invitation; Sponsor: AbbVie; N=160 ➔ 200; Initiation date: Oct 2015 ➔ Jan 2015

Clinical • Enrollment change • P2 data • Trial initiation date • Immunology • Inflammation • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CRP

A Phase 2, Multicenter Open-Label Extension (OLE) Study With ABT-122 in Active Psoriatic Arthritis Subjects Who Have Completed a Preceding Study M14-197 (clinicaltrials.gov) - P2; N=110; Not yet recruiting; Sponsor: AbbVie

Clinical • New P2 trial • P2 data • Immunology • Inflammation • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CRP

A Phase 2, Multicenter Open-Label Extension (OLE) Study With ABT-122 in Active Psoriatic Arthritis Subjects Who Have Completed a Preceding Study M14-197 (clinicaltrials.gov) - P2; N=160; Enrolling by invitation; Sponsor: AbbVie; N=110 ➔ 160

Clinical • Enrollment change • P2 data • Immunology • Inflammation • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CRP

A Phase 2, Multicenter Open-Label Extension (OLE) Study With ABT-122 in Active Psoriatic Arthritis Subjects Who Have Completed a Preceding Study M14-197 (clinicaltrials.gov) - P2; N=200; Active, not recruiting; Sponsor: AbbVie; Enrolling by invitation ➔ Active, not recruiting; Initiation date: Jan 2015 ➔ Oct 2015

Clinical • Enrollment closed • P2 data • Trial initiation date • Immunology • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CRP

Pharmacological treatment of psoriatic arthritis: a systematic literature research for the 2019 update of the EULAR recommendations for the management of psoriatic arthritis. (PubMed, Ann Rheum Dis) - "Many drugs in PsA are available and have demonstrated efficacy against placebo. Efficacy varies across PsA manifestations. Safety must also be taken into account. This review informed the development of the European League Against Rheumatism 2019 updated PsA management recommendations."

Journal • CNS Disorders • Immunology • Multiple Sclerosis • Psoriasis • Psoriatic Arthritis • Pulmonary Embolism • Rheumatology • Venous Thromboembolism

Fourteen small molecule and biological agents for psoriatic arthritis: A network meta-analysis of randomized controlled trials. (PubMed, Medicine (Baltimore)) - "Direct and indirect comparisons and integrated results suggested that the 3 anti- tumor necrosis factor -α biologics (GOL, ETN, and IFX) can be considered the best treatments for PsA after comprehensive consideration of efficacy and safety."

Journal • Retrospective data • Dermatology • Dermatopathology • Immunology • Psoriasis • Psoriatic Arthritis • Rheumatology

A Phase 2 Study to Investigate the Safety and Efficacy of ABT-122 Given With Methotrexate in Subjects With Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate (clinicaltrials.gov) - P2; N=225; Active, not recruiting; Sponsor: AbbVie; N=160 ➔ 225

Enrollment change • Biosimilar • Immunology • Inflammation • Rheumatoid Arthritis

An update on pathogenesis of psoriatic arthritis and potential therapeutic targets. (PubMed, Expert Rev Clin Immunol) - "Specifically, we reviewed data on IL-17 inhibitors, abatacept, JAK inhibitors, ABT 122, and A (3) adenosine receptors agonist, CF101. Expert opinion: In PsA an intriguing pathogenetic network has been documented. Several biological and synthetic drugs are promising in terms of efficacy and safety profile."

Journal • Immunology • Psoriasis • Psoriatic Arthritis • Rheumatology

AbbVie: Strategy Presentations (AbbVie) - Anticipated initiation of P2 trial for psoriasis in Q4 2015-2016; Anticipated initiation of P3 trial for rheumatoid arthritis in Q4 2015-2016

Anticipated new P2 trial • Anticipated new P3 trial • Psoriasis • Rheumatoid Arthritis

Dual blockade of interleukin 1β and interleukin 17A reduces murine arthritis pathogenesis but also leads to spontaneous skin infections in non-human primates. (PubMed, J Pharmacol Exp Ther) - "...Given the potential clinical benefit in RA, we generated a human dual variable domain antibody (DVD-Ig), ABBV-615, capable of simultaneous binding and neutralization of IL-1β and IL-17A...Consistent with reduced resistance to skin infections, IL-1β and IL-17A-stimulated human keratinocytes demonstrate cooperative or compensatory production of key anti-bacterial and inflammatory mediators such as Lipocalin-2 (LCN2), G-CSF, CXCL1, IL-8, tumor necrosis factor (TNF) and IL-6, which aid in defense against skin bacterial infections. These results illustrate the skin-specific antimicrobial mechanisms of IL-1β and IL-17A and highlight the importance of understanding unique combinatorial effects of biological agents."

Journal • Preclinical • Biosimilar • Immunology • Ophthalmology • Rheumatoid Arthritis

AbbVie: Q1 FY 2016 Results (AbbVie) - Anticipated presentation of data from P2 trial (NCT02349451) in psoriatic arthritis at ACR (November 11-16, 2016); Anticipated presentation of data from P2 trial (NCT02141997) in RA at ACR

Anticipated P2 data • Psoriasis • Rheumatoid Arthritis

A novel tetravalent bispecific antibody targeting programmed death 1 and tyrosine-protein kinase Met for treatment of gastric cancer. (PubMed, Invest New Drugs) - "Methods We developed two novel BsAbs PD-1/c-Met DVD-Ig and IgG-scFv both targeting PD-1 to restore the immune effector function of T cells and engaging them to tumor cells via binding to cellular-mesenchymal to epithelial transition factor (c-Met)...Results These bispecific antibodies exhibited effective antitumor activity against high- and low- c-Met-expressing gastric cancer cell lines in vitro and mediated strong tumor growth inhibition in human gastric cancer xenograft models. Conclusion The engagement of the PD-1/PD-L1 blockade to c-Met-overexpressing cancer cells is a promising strategy for the treatment of gastric cancer and potentially other malignancies."

Journal

Population Pharmacokinetics of the TNF-α and IL-17A Dual-Variable Domain Antibody ABT-122 in Healthy Volunteers and Subjects With Psoriatic or Rheumatoid Arthritis: Analysis of Phase 1 and 2 Clinical Trials. (PubMed, J Clin Pharmacol) - "Fixed-effects and random-effects parameters were estimated with a relative standard error of ≤17% and ≤28%, respectively, and the model was qualified using bootstrap analysis and visual predictive checks. This analysis characterized ABT-122 exposure across populations and supported exposure-response analyses of ABT-122 efficacy in RA and PsA."

Clinical • Journal • P1 data • PK/PD data

Exposure-response analyses demonstrate no evidence of interleukin 17A contribution to efficacy of ABT-122 in rheumatoid or psoriatic arthritis. (PubMed, Rheumatology (Oxford)) - P2; "The objective of this work was to characterize exposure-response relationships for ABT-122 relative to adalimumab (TNF-α inhibitor) using ABT-122 phase 2 trials in patients with RA or PsA. Overall, there was no clear evidence that inhibition of the IL-17 pathway provided incremental benefit in the presence of TNF-α inhibition. ClinicalTrials.gov, NCT02433340, NCT02349451."

Clinical • Journal

Psoriatic arthritis : Drugs of the (near) future (PubMed, Z Rheumatol) - "Results have already been obtained from phase 3 studies for tofacitinib, a Janus kinase inhibitor as well as for the antibodies brodalumab, bimekizumab and ABT-122 that inhibit the IL17-signaling pathway. The sphingolipid agonist ponesimod and the A3AR agonist CF101 represent "small molecules" similar to the Janus kinase inhibitors that will potentially extend the therapeutic options in the future."

Journal • Review

Pharmacokinetics of ABT-122, a TNF-α- and IL-17A-Targeted Dual-Variable Domain Immunoglobulin, in Healthy Subjects and Patients with Rheumatoid Arthritis: Results from Three Phase I Trials. (PubMed, Clin Pharmacokinet) - P1; "Results from these three phase I studies supported testing ABT-122 every week and every other week regimens in phase II trials in subjects with rheumatoid and psoriatic arthritis. Study 2 (EudraCT: 2012-003448-54); Study 3 (NCT01853033)."

Journal