romilkimab (SAR156597) / Sanofi - LARVOL DELTA

Molecular Features and Stages of Pulmonary Fibrosis Driven by Type 2 Inflammation. (PubMed, Am J Respir Cell Mol Biol) - "While a recent proof-of-concept study using Romilkimab or SAR156597, a bi-specific IL-4/IL-13 antibody, suggests a direct role of these cytokines in the pathophysiology of SSc, their contributions to the balance between inflammation and fibrosis are unclear...These data recapitulate important features of fibrotic-progression in lungs of SSc-ILD patients and enhance our understanding of the progressive pathobiology of SSc. This study also further establishes FRA2-Tg mice as a valuable tool for testing future therapeutic agents in SSc-ILD."

Journal • Eosinophilia • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Inflammation • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis • IL13 • IL4

Impact of Innovative Treatment Using Biological Drugs for the Modulation of Diffuse Cutaneous Systemic Sclerosis: A Systematic Review. (PubMed, Medicina (Kaunas)) - "The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included original articles in English and Spanish with a controlled trial design, comparing biological drug treatments (tocilizumab, belimumab, riociguat, abatacept, and romilkimab) with a control group. Biological drugs, therefore, maybe a new therapeutic strategy for dcSSc and could be recommended as an additional and/or adjunctive treatment that promotes anti-fibrotic activity. This review could further define the clinical rationale for the use of biologics in the treatment of dcSSc and could provide key details on the study protocol, design, and outcome reporting."

Journal • Review • Dermatology • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

"Bi-Specific MAbS Global Markets Report 2022: Catumaxomab (Removab); Blinatumomab; Duligotumab; SAR 156597 - https://t.co/guyiBzPH8C https://t.co/JSM8iv4IFN" (@NewsFromBW)

Contribution of monocytes and macrophages to the pathogenesis of systemic sclerosis: recent insights and therapeutic implications. (PubMed, Curr Opin Rheumatol) - "Through their potential pro-fibrotic and pro-inflammatory properties, macrophages are at the cross-road of key SSc pathogenic processes and associated manifestations. Investigative drugs targeting macrophage polarization, such as pan-janus kinase inhibitors (tofacitinib or ruxolitinib) impacting both M1 and M2 activations, or Romilkimab inhibiting IL-4 and IL-13, have shown promising results in preclinical models or phase I/II clinical trials in SSc and other fibro-inflammatory disorders. Macrophage-based cellular therapy may also represent an innovative approach for the treatment of SSc, as initial training of macrophages may modulate the severity of fibrotic and autoimmune manifestations of the disease."

Journal • Fibrosis • Immunology • Inflammation • Scleroderma • Systemic Sclerosis • CD52 • FCGR3A • IL13 • IL4 • SPP1

An update on targeted therapies in systemic sclerosis based on a systematic review from the last 3 years. (PubMed, Arthritis Res Ther) - "The drugs studied in phase 1/phase 2 studies included the following: inebilizumab, dabigatran, C-82, pomalidomide, rilonacept, romilkimab, tocilizumab, tofacitinib, pirfenidone, lenabasum, abatacept, belimumab, riociguat, SAR100842 and lanifibranor...Phase 3 clinical trials investigated nintedanib and tocilizumab...Two observational studies including > 50 patients with rituximab as the targeted drug were also evaluated. All these studies offer a real hope for SSc patients. The future challenges will be to customize patient-specific therapeutics with the goal to develop precision medicine for SSc."

Journal • Review • Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

Novel Biologic Promising in Mid-Stage Scleroderma Trial (MedPageToday) - "'This was a really interesting study looking at a novel strategy for patients with early diffuse systemic sclerosis, which is a real challenge in terms of identifying effective therapies,' commented Robert Spiera...'Those are cytokines that are felt to be important in the cellular immune response, which is very relevant to scleroderma pathophysiology,' Spiera said....'This was a trial design that is very impressive to me in the sense that they did what we do in the real world, which was to allow background therapy,' Spiera said....'It definitely showed signals of efficacy and was acceptable in terms of safety. This would warrant a further look in a large phase III clinical trial,' Spiera said."

Media quote

Romilkimab: Regulatory submission for systemic scleroderma in 2023 or beyond (Sanofi) - Q3 2020 Results

Regulatory • Systemic Sclerosis

"So tocilizumab favors more lung and romilkimab more skin looks like so far" (@chandanakeshav1)

A randomised, double-blind, placebo-controlled, 24-week, phase II, proof-of-concept study of romilkimab (SAR156597) in early diffuse cutaneous systemic sclerosis. (PubMed, Ann Rheum Dis) - P2 | "This study demonstrated significant effects on skin changes with romilkimab in early dcSSc that require confirmation with a longer and more comprehensive phase III study to determine clinical relevance."

Clinical • Journal • P2 data • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Scleroderma • Systemic Sclerosis

'Future therapies' in clinical trials may revise ability to treat systemic sclerosis (Healio) - "'There have been a huge number of therapeutic targets - peptide and small molecule mediators, immune cell subpopulations and co-stimulatory mediators, cytokines, integrins - all of which have been tried or are being considered to treat systemic sclerosis in one aspect or another,' Daniel E. Furst, MD...'There are three interesting future therapies that I would like to talk about today: lenabasum, pirfenidone and romilkimab.'"

Media quote • Systemic Sclerosis

[VIRTUAL] FIRST CASE OF AUTOLOGOUS STEM CELL TRANSPLANTATION FOR SYSTEMIC SCLEROSIS IN ESTONIA (SSWC 2020) - "In March 2017 mRSS progressed to 28/51 and CyA was switched to azathioprine. From June to December 2017 she participated in clinical trial ACT14604 ( SAR156597/placebo) with favourable results.In March 2018 dyspnoea worsened, walking capacity reduced from 8 to 2km...IV Cyclophosphamide (7 infusions (7105mg) until August 2018) was ineffective: mRSS 17/51, lesions developed in 3 fingers, DLCO 52,5%, FCV 3.12l, CT showed more ground glass opacities.The patient consented with ASCT... The first case of ASCT for SScl in Estonia performed on 15January2019 in North Estonia Medical Centre can be considered successful with no short-term complications and fast resolvement of skin and lung involvement. Further follow-up is needed for long-term resul"

Clinical • Systemic Sclerosis • FBL • MRI

[VIRTUAL] EFFICACY AND SAFETY OF ROMILKIMAB IN DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS (DCSSC): RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 24-WEEK, PROOF OF CONCEPT STUDY (EULAR 2020) - P2 | "Patients with dcSSc who were treated with RKB showed a statistically significant reduction in mRSS compared to those receiving PBO. Secondary outcomes were not met, although RKB was associated with a smaller decline in FVC than PBO. Post-hoc analysis showed a possible reduction on time to progression with RKB."

Clinical • Cardiovascular • Pain • Scleroderma • Systemic Sclerosis • IL13 • IL4

To evaluate the effect of different doses of SAR156597 given to patients with idiopathic pulmonary fibrosis (IPF) (clinicaltrials.gov) - P1/2, N=24; Not yet recruiting -> Recruiting

Enrollment open • Fibrosis • Immunology

Early development of SAR156597, an innovative bi-specific IL-4/IL-13 antibody as a potential treatment for idiopathic pulmonary fibrosis (ICLAF 2012) - SAR156597 has entered early clinical development for the treatment of IPF & was found to be safe and well-tolerated following single ascending subcutaneous doses in healthy subjects; A prospective biomarker study is being conducted in IPF pts, in parallel of the phase 1, to evaluate the natural history of the disease, & to identify biomarkers of disease progression

Review • Fibrosis • Immunology

Q3 2017 business EPS(1) up 1.1% at CER(2) FY 2017 guidance confirmed (Sanofi Press Release) - "Sanofi decided to stop the development of SAR156597 in Idiopathic Pulmonary Fibrosis."

Discontinued • Idiopathic Pulmonary Fibrosis • Immunology • Respiratory Diseases

SAR156597: Submission in systemic scleroderma in 2022 or later (Sanofi) - Q4 FY2017 Results

Regulatory • Immunology • Systemic Sclerosis

Sanofi at forefront of fight against COVID-19 in Q1 2020 (GlobeNewswire, Sanofi) - "First-quarter 2020 Pharmaceutical sales were up 7.5% to €6,764 million, mainly driven by Dupixent...Dupixent® is also launched in adolescent atopic dermatitis in 12 countries, in asthma in 14 countries and in CRSwNP in 5 countries. Potentially as many as 68 additional country launches are planned across these indications in the remainder of 2020....Kevzara® (collaboration with Regeneron) sales were €55 million (up 80.0%) in the first quarter, of which €32 million was generated in the U.S. (up 72.2%) and €20 million in Europe (150.0%)....Anticipated regulatory submission of romilkimab for Systemic scleroderma in 2023 and beyond....Dupixent: Part A readout from pivotal trial in Eosinophilic Esophagitis in Q2-Q3 2020; Pivotal trial read-out in Asthma for 6-11 year old age group in Q4 2020....Anticipated regulatory submission for AD 6m - 5y old in 2022."

BLA • Clinical data • Regulatory • Sales • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation

SAR156597: Regulatory submission for systemic scleroderma in 2023 or later (Sanofi) - Q1 2020 Results

Regulatory • Immunology • Systemic Sclerosis

Bispecific Antibodies for Autoimmune and Inflammatory Diseases: Clinical Progress to Date. (PubMed, BioDrugs) - "The clinical evaluation of bsAbs in autoimmune diseases is ongoing, with both successes (phase II trials of obexelimab in systemic lupus erythematosus) and failures (phase II trials of lutikizumab in osteoarthritis and romilkimab in idiopathic pulmonary fibrosis), and this review aims to provide a comprehensive, up-to-date summary of the clinical progress of bsAbs in this therapeutic area. Although many challenges remain, bsAbs offer new therapeutic options in the future direction of autoimmune disease treatments."

Clinical • Journal

SAR156597 in idiopathic pulmonary fibrosis: a phase 2, placebo-controlled study (DRI11772). (PubMed, Eur Respir J) - P2; "The mean change from baseline in percent-predicted FVC at 52 weeks was -5.8%, -5.2% and -6.3% for the placebo, Q2W and QW arms, respectively (Q2W versus placebo, p=0.59; QW versus placebo, p=0.63). The safety profile observed in the three treatment arms was generally similar, although serious adverse events were more common in the QW arm than in the other arms.The DRI11772 study failed to demonstrate a benefit for SAR156597 in the treatment of IPF."

Clinical • Journal • P2 data

Efficacy and Safety of Romilkimab in Diffuse Cutaneous Systemic Sclerosis (dcSSc): A Randomized, Double-Blind, Placebo-Controlled, 24-week, Proof of Concept Study (ACR-ARHP 2019) - P2; "Patients with dcSSc who were treated with RKB showed a statistically significant reduction in mRSS compared to those receiving placebo. None of the secondary outcomes were met, although RKB was associated with a smaller decline in FVC than placebo. Romilkimab was well tolerated with no major safety concerns."

Clinical

SAR156597: Regulatory submission in systemic scleroderma in 2023 or later (Sanofi) - Q3 2019 Results

Regulatory

SAR156597: Regulatory submission in systemic scleroderma in 2023 or later (Sanofi) - Q1 2019 Results

Regulatory

SAR156597: Data from P2a trial (NCT02921971) for scleroderma in 2019 (Sanofi) - Q1 2019 Results

P2a data

Effectiveness and Safety of SAR156597 in Treating Diffuse Systemic Sclerosis (clinicaltrials.gov) - P2; N=97; Completed; Sponsor: Sanofi; Active, not recruiting ➔ Completed; Trial primary completion date: Oct 2018 ➔ Jan 2019

Clinical • Trial completion • Trial primary completion date