CJM112 / Novartis - LARVOL DELTA

Next-Generation Anti-IL-17 Agents for Psoriatic Disease: A Pipeline Review. (PubMed, Am J Clin Dermatol) - "Key agents under investigation include netakimab, vunakizumab, xeligekimab, gumokimab, HB0017, CJM 112, JS005, 608, LZM012, ZL-1102, izokibep, sonelokimab, DC-806, DC-853, and LEO 153339. Both preclinical and clinical trial data for each agent are summarized, with an emphasis on their efficacy, adverse effects, immunogenicity, and future outlooks."

Journal • Dermatology • Immunology • Inflammatory Arthritis • Psoriasis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies

Interleukin-17: A pleiotropic cytokine implicated in inflammatory, infectious, and malignant disorders. (PubMed, Cytokine Growth Factor Rev) - "Four FDA-approved drugs-secukinumab (for ankylosing spondylitis, enthesitis-related arthritis, hidradenitis suppurativa, non-radiographic axial spondyloarthritis, plaque psoriasis, and psoriatic arthritis), ixekizumab (for ankylosing spondylitis, non-radiographic axial spondyloarthritis, plaque psoriasis, and psoriatic arthritis), brodalumab (for plaque psoriasis), and bimekizumab (for plaque psoriasis)-suppress the IL-17 pathway, with more in development, including netakimab, sonelokimab, izokibep, and CJM112. These agents and others are being studied across a spectrum of disorders. Understanding the complicated interplay between IL-17 and other immune mediators may yield new treatments for inflammatory/autoimmune conditions and malignancies."

Journal • Ankylosing Spondylitis • Dermatology • Genetic Disorders • Hidradenitis Suppurativa • Idiopathic Arthritis • Immunology • Infectious Disease • Inflammatory Arthritis • Oncology • Psoriasis • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Skin Cancer • Solid Tumor • Spondylarthritis • IL17A • IL17C • IL17RA • IL23A

Safety and efficacy of IL-17 inhibitors in hidradenitis suppurativa: an updated systematic review and meta-analysis including the BE-HEARD trials. (PubMed, Arch Dermatol Res) - No abstract available

Journal • Retrospective data • Review • Dermatology • Hidradenitis Suppurativa • Immunology • IL17A

The use of biologics and JAK inhibitors in the management of moderate to severe Hidradenitis Suppurativa treatment: a scoping review. (PubMed, Arch Dermatol Res) - "Secukinumab and adalimumab were identified as the only two drugs approved by the FDA for treating moderate to severe HS in adults...IL-12/23 inhibitor ustekinumab demonstrated improvements in disease severity scores and HiSCR rates in small trials. IL-17 inhibitors such as brodalumab, bimekizumab, and CJM112 showed preliminary positive responses in early-phase clinical studies and case reports. While evidence was mixed, some TNF-α inhibitors such as infliximab provided benefits according to a randomized controlled trial, though etanercept trials yielded non-significant or inconsistent findings. Larger, well-designed studies are required to further establish their efficacy and safety, but biologics and JAKis show potential as alternative treatment options for moderate to severe HS. The findings of this review contribute to the growing interest among patients and to enhancing the understanding of physician's regarding potential alternative therapeutic options for HS..."

Journal • Review • Dermatology • Hidradenitis Suppurativa • Immunology • IL12A • IL17A

Comparative efficacy and therapeutic positioning of biologics in hidradenitis suppurativa: A systematic review with network meta-analysis of randomised trials. (PubMed, Indian J Dermatol Venereol Leprol) - "The NMA showed the odds of achieving the clinical response were significantly superior with adalimumab (RR: 0.37, 95% CI = 0.06-0.63), adalimumab QW (RR: 0.63, 95% CI = 0.43-0.87), MAB1p (RR: 1.33, 95% CI = 0.03-3.12), secukinumab (RR: 0.25, 95% CI = 0.11-0.47) and secukinumabQ2W (RR: 0.24, 95% CI = 0.1-0.46) compared to placebo...Data for bimekizumab and CJM112 are promising. Infliximab has inconsistent clinical response, and more data are necessary to confirm this molecule as a potential third-line therapy in HS. The blockade of IL-23 and CD5a pathways is not relevant, or at least the current evidence is insufficient to recommend further investigation of guselkumab, risankizumab, and vilobelimab in phase III trials."

Journal • Retrospective data • Review • Dermatology • Hidradenitis Suppurativa • Immunology • Oncology • IL23A

IL-17 Inhibition: A Valid Therapeutic Strategy in the Management of Hidradenitis Suppurativa. (PubMed, Pharmaceutics) - "Indeed, adalimumab, an anti-tumor necrosis factor (TNF)-α monoclonal antibody, is the only approved biologic agent for HS, obtaining a therapeutic response in only 50% of HS patients...Both bimekizumab and secukinumab, targeting IL-17 in different manners, have successfully completed phase III trials with promising results; the latter has recently been approved by EMA for the treatment of HS. The aim of this review is to summarize the current state of knowledge concerning the relevant role of IL-17 in HS pathogenesis, highlighting the key clinical evidence of anti-IL-17 agents in the treatment of this disease."

Journal • Review • Dermatology • Hidradenitis Suppurativa • Immunology • Oncology • IL17A • TNFA

Anti-IL-17A blockade did not significantly reduce inflammatory lesions in a placebo-controlled pilot study in adult patients with moderate to severe acne. (PubMed, J Dermatolog Treat) - "CJM112 is a potent anti-IL-17A monoclonal antibody, whose clinical efficacy in psoriasis was recently documented...Additionally, no differences were observed between groups in other secondary and exploratory endpoints at Week 12. Anti-IL-17A therapy was not significantly different compared to the placebo in reducing inflammatory lesions in patients with moderate to severe acne."

Journal • Acne Vulgaris • Dermatology • Immunology • Psoriasis

Study of Efficacy and Safety of CJM112 in Patients With Moderate to Severe Inflammatory Acne (clinicaltrials.gov) - P2 | N=52 | Completed | Sponsor: Novartis Pharmaceuticals | Terminated ➔ Completed

Trial completion • Acne Vulgaris • Dermatology

Biologics and Small Molecule Inhibitors for Treating Hidradenitis Suppurativa: A Systematic Review and Meta-Analysis. (PubMed, Biomedicines) - "Adalimumab and bimekizumab are the only two biologics effective in achieving HiSCR with acceptable safety profile, whereas adalimumab is the only biologic effective in achieving DLQI 0/1."

Journal • Retrospective data • Review • Dermatology • Hidradenitis Suppurativa

IL-17A is a pertinent therapeutic target for moderate to severe hidradenitis suppurativa: combined results from a pre-clinical and Phase II proof-of-concept study. (PubMed, Exp Dermatol) - "This study elucidated the role of the IL-17A pathway in HS pathogenesis and clinically validated the IL-17A pathway in moderate to severe HS patients in a proof-of-concept study using the anti-IL-17A-specific antibody CJM112."

Clinical • Journal • P2 data • Preclinical • Dermatology • Dermatopathology • Hidradenitis Suppurativa • IL17A

A Study of PDR001 in Combination With CJM112, EGF816, Ilaris® (Canakinumab) or Mekinist® (Trametinib) (clinicaltrials.gov) - P1; N=289; Completed; Sponsor: Novartis Pharmaceuticals; Active, not recruiting ➔ Completed

Clinical • Combination therapy • Trial completion • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Immune Modulation • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • FOXP3

First-in-human study demonstrating the safety and clinical efficacy of novel anti-IL-17A monoclonal antibody CJM112 in moderate to severe plaque psoriasis. (PubMed, J Eur Acad Dermatol Venereol) - "CJM112 had clinical efficacy in moderate to severe psoriasis and was generally safe and well tolerated in the doses tested. Additional neutralization of IL-17AF did not translate to increased clinical efficacy compared with secukinumab."

Clinical • Journal • P1 data • Dermatology • Immunology • Psoriasis • IL17A

A Study of PDR001 in Combination With CJM112, EGF816, Ilaris® (Canakinumab) or Mekinist® (Trametinib) (clinicaltrials.gov) - P1; N=290; Active, not recruiting; Sponsor: Novartis Pharmaceuticals; Trial completion date: Nov 2020 ➔ Mar 2021; Trial primary completion date: Nov 2020 ➔ Mar 2021

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Immune Modulation • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Pharmacological development in hidradenitis suppurativa. (PubMed, Curr Opin Pharmacol) - "So far TNF inhibition with adalimumab remains the only EMA-approved/FDA-approved agent in HS treatment and should be consequently considered first. In recent years, new phase II and III trials for HS management have appeared aimed at inhibition of specific targetable inflammatory pathways identified in HS. Thus, several new biologics are being investigated, including MABp1 (bermekimab), CJM112, bimekizumab, guselkumab, secukinumab, and IFX-1."

Journal • Review • Dermatology • Dermatopathology • Hidradenitis Suppurativa • Immunology

Study of Single Agent CJM112, and PDR001 in Combination With LCL161 or CJM112 in Patients With Multiple Myeloma (clinicaltrials.gov) - P1; N=70; Not yet recruiting; Sponsor: Novartis Pharmaceuticals; Trial primary completion date: Mar 2020 ➔ Dec 2018

Trial primary completion date • Biosimilar • Hematological Malignancies • Multiple Myeloma • Oncology

CJM112: Regulatory filing for immune disorders in 2021 or later (Novartis) - Investor Event

Regulatory • Psoriasis

Study of Single Agent CJM112, and PDR001 in Combination With LCL161 or CJM112 in Patients With Multiple Myeloma (clinicaltrials.gov) - P1; N=26; Completed; Sponsor: Novartis Pharmaceuticals; Active, not recruiting ➔ Completed

Clinical • Combination therapy • Trial completion • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

A Study of PDR001 in Combination With CJM112, EGF816, Ilaris® (Canakinumab) or Mekinist® (Trametinib) (clinicaltrials.gov) - P1; N=290; Active, not recruiting; Sponsor: Novartis Pharmaceuticals; Trial completion date: Jan 2020 ➔ Jun 2020; Trial primary completion date: Jan 2020 ➔ Jun 2020

Clinical • Combination therapy • Trial completion date • Trial primary completion date • CD8 • FOXP3 • TIL

Study to Assess the Efficacy and Safety of CJM112 in Patients With Inadequately Controlled Severe Asthma (clinicaltrials.gov) - P2; N=118; Completed; Sponsor: Novartis Pharmaceuticals; Recruiting ➔ Completed

Clinical • Trial completion

A Study of PDR001 in Combination With CJM112, EGF816, Ilaris® (Canakinumab) or Mekinist® (Trametinib) (clinicaltrials.gov) - P1; N=290; Active, not recruiting; Sponsor: Novartis Pharmaceuticals; Recruiting ➔ Active, not recruiting; N=432 ➔ 290; Trial completion date: May 2020 ➔ Jan 2020; Trial primary completion date: May 2020 ➔ Jan 2020

Clinical • Combination therapy • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date

Study of Single Agent CJM112, and PDR001 in Combination With LCL161 or CJM112 in Patients With Multiple Myeloma (clinicaltrials.gov) - P1; N=26; Active, not recruiting; Sponsor: Novartis Pharmaceuticals; Recruiting ➔ Active, not recruiting; N=70 ➔ 26

Clinical • Combination therapy • Enrollment change • Enrollment closed

Study of Single Agent CJM112, and PDR001 in Combination With LCL161 or CJM112 in Patients With Multiple Myeloma (clinicaltrials.gov) - P1; N=70; Recruiting; Sponsor: Novartis Pharmaceuticals; Trial completion date: Sep 2019 ➔ Mar 2020; Trial primary completion date: Sep 2019 ➔ Mar 2020

Clinical • Combination therapy • Trial completion date • Trial primary completion date

Systematic review of immunomodulatory therapies for hidradenitis suppurativa. (PubMed, Biologics) - "...Published data from clinical trials support the efficacy of adalimumab, infliximab, anakinra, ustekinumab, bermekimab and apremilast but not etanercept and MEDI8968. Clinical trials for CJM112 have been completed, with results awaiting publication. Trials are underway for secukinumab, IFX-1, INCB054707 and bimekizumab. Biologics used in smaller cohorts include canakinumab, golimumab and rituximab...Different clinical measurement scores and endpoints used to make direct comparison difficult. Longitudinal surveillance and pooled registry data are paramount to evaluate the long-term safety profile and efficacy of therapy."

Journal • Review

Study of Single Agent CJM112, and PDR001 in Combination With LCL161 or CJM112 in Patients With Multiple Myeloma (clinicaltrials.gov) - P1; N=70; Recruiting; Sponsor: Novartis Pharmaceuticals; Trial completion date: May 2020 ➔ Sep 2019; Trial primary completion date: May 2020 ➔ Sep 2019

Clinical • Combination therapy • Trial completion date • Trial primary completion date

A Study of PDR001 in Combination With CJM112, EGF816, Ilaris® (Canakinumab) or Mekinist® (Trametinib) (clinicaltrials.gov) - P1; N=432; Recruiting; Sponsor: Novartis Pharmaceuticals; Trial completion date: Feb 2020 ➔ May 2020; Trial primary completion date: Feb 2020 ➔ May 2020

Clinical • Combination therapy • PD(L)-1 Biomarker • Trial completion date • Trial primary completion date