Efficacy and Safety of SAR156597 in the Treatment of Diffuse Cutaneous Systemic Sclerosis (dcSSc): A Randomized, Double-blind, Placebo-controlled, 24-week, Proof of Concept Study

Primary Objective:
To evaluate, in comparison with placebo, the efficacy of SAR156597 administered subcutaneously for 24 weeks on skin fibrosis in participants with diffuse cutaneous systemic sclerosis (dcSSc).
Secondary Objectives:
To evaluate the efficacy of SAR156597 compared to placebo on physical/functional disability in participants with dcSSc.
To evaluate the efficacy of SAR156597 compared to placebo on respiratory function of participants with dcSSc.
To evaluate the safety profile of SAR156597 compared to placebo in participants with dcSSc.
To evaluate the potential for immunogenicity (anti-drug antibodies response) of SAR156597 in participants with dcSSc.
To evaluate the pharmacokinetics (trough plasma concentrations) of SAR156597 administered subcutaneously for 24 weeks.

Start Date21 Dec 2016

Sponsor / Collaborator

Sanofi SA

NCT02345070

/ CompletedPhase 2

Efficacy and Safety of SAR156597 in the Treatment of Idiopathic Pulmonary Fibrosis (IPF): A Randomized, Double-blind, Placebo-controlled, 52-week Dose-ranging Study

Primary Objective:
To evaluate, in comparison with placebo, the efficacy of 2 dose levels/regimens of SAR156597 administered subcutaneously during 52 weeks on lung function of participants with Idiopathic Pulmonary Fibrosis (IPF).
Secondary Objectives:
To evaluate the efficacy of 2 dose levels/regimens of SAR156597 compared to placebo on IPF disease progression.
To evaluate the safety of 2 dose levels/regimens of SAR156597 compared to placebo in participants with IPF.

Start Date01 May 2015

Sponsor / Collaborator

Sanofi

NCT01529853

/ CompletedPhase 1/2

Randomized, Double-blind, Placebo-controlled Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Ascending Repeated Doses of SAR156597 in Patients With Idiopathic Pulmonary Fibrosis (IPF)

Primary Objective:
To assess in adult patients with Idiopathic Pulmonary Fibrosis (IPF) the safety and tolerability of ascending doses of SAR156597 administered subcutaneously (SC) once weekly over a 6-week period.
Secondary Objectives:
To assess in adult patients with IPF:
The pharmacodynamic effects of SAR156597, as measured on pulmonary function tests (PFTs), pulse oximetry and patient reported outcome and peripheral blood biomarkers.
The trough plasma concentrations of SAR156597
The potential immunogenicity of SAR156597.

Start Date01 Jan 2012

Sponsor / Collaborator

Sanofi

100 Clinical Results associated with Romilkimab

100 Translational Medicine associated with Romilkimab

100 Patents (Medical) associated with Romilkimab

Literatures (Medical) associated with Romilkimab

01 Oct 2023·American journal of respiratory cell and molecular biology

Molecular Features and Stages of Pulmonary Fibrosis Driven by Type 2 Inflammation.

Article

Author: Cummings, Sheila ; Mattoo, Hamid ; Bangari, Dinesh S ; Savova, Virginia ; Nestle, Frank O ; Beil, Christian ; Subramaniam, Arun ; Habiel, David ; Bryce, Paul J ; Resnick, Robert ; Xu, Ethan Y ; Humulock, Zachary ; Pate, Nathan ; Qian, George ; Rao, Ercole

Systemic sclerosis (SSc) is a progressive, multiorgan disease with limited treatment options. Although a recent proof-of-concept study using romilkimab or SAR156597, a bispecific 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. Here, we determine the roles of type 2 inflammation in fibrogenesis using FRA2-Tg (Fos-related antigen 2-overexpressing transgenic) mice, which develop spontaneous, age-dependent progressive lung fibrosis. We defined the molecular signatures of inflammation and fibrosis at three key stages in disease progression, corresponding to preonset, inflammatory dominant, and fibrosis dominant biology, and revealed an early increase in cytokine-cytokine receptor interactions and antigen-processing and presentation pathways followed by enhanced Th2- and M2 macrophage-driven type 2 responses. This type 2 inflammation progressed to extensive fibrotic pathology by 14-18 weeks of age, with these gene signatures overlapping significantly with those seen in the lungs of patients with SSc with interstitial lung disease (ILD). These changes were also evident in the histopathology, which showed perivascular and peribronchiolar inflammation with prominent eosinophilia and accumulation of profibrotic M2-like macrophages followed by rapid progression to fibrosis with thickened alveolar walls with multifocal fibrotic bands and signs of interstitial pneumonia. Critically, treatment with a bispecific antibody targeting IL-4 and IL-13 during the inflammatory phase abrogated the Th2 and M2 responses and led to near-complete abrogation of lung fibrosis. These data recapitulate important features of fibrotic progression in the lungs of patients with SSc-ILD 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.

01 Dec 2021·Arthritis Research & TherapyQ2 · MEDICINE

An update on targeted therapies in systemic sclerosis based on a systematic review from the last 3 years

Q2 · MEDICINE

ReviewOA

Author: Allanore, Yannick ; Campochiaro, Corrado

AbstractNew molecular mechanisms that can be targeted with specific drugs have recently emerged for the treatment of systemic sclerosis (SSc) patients. Over the past 3 years, the achievement of one large phase 3 trial has led to the approval by drug agencies of the first drug licenced for SSc-related interstitial lung disease. Given this exciting time in the SSc field, we aimed to perform a systemic literature review of phase 1, phase 2 and phase 3 clinical trials and large observational studies about targeted therapies in SSc. We searched MEDLINE/PubMed, EMBASE, and ClinicalTrials.gov for clinical studies from 2016 with targeted therapies as the primary treatment in patients with SSc for skin or lung involvement as the primary clinical outcome measure. Details on the study characteristics, the trial drug used, the molecular target engaged by the trial drug, the inclusion criteria of the study, the treatment dose, the possibility of concomitant immunosuppression, the endpoints of the study, the duration of the study and the results obtained were reviewed. Of the 973 references identified, 21 (4 conference abstracts and 17 articles) were included in the systematic review. A total of 15 phase 1/phase 2 clinical trials, 2 phase 3 clinical trials and 2 observation studies were analysed. 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. All but 3 studies were performed in early diffuse SSc patients with different inclusion criteria, while 3 studies were performed in SSc patients with interstitial lung disease (ILD). Phase 3 clinical trials investigated nintedanib and tocilizumab. Nintedanib was investigated in SSc-ILD patients whereas tocilizumab focused on early diffuse SSc patients with inflammatory features. 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.

01 Nov 2021·Current Opinion in RheumatologyQ2 · MEDICINE

Contribution of monocytes and macrophages to the pathogenesis of systemic sclerosis: recent insights and therapeutic implications

Q2 · MEDICINE

Review

Author: Lescoat, Alain ; Lecureur, Valérie ; Varga, John

Purpose of reviewTo discuss recent studies addressing the role of monocytes and macrophages in the pathogenesis of systemic sclerosis (SSc) based on human and mouse models.Recent findingsStudies indicate that monocyte adhesion could be increased in SSc secondary to an interferon-dependent loss of CD52, and chemotaxis up-regulated through the CCR3/CCL24 pathway. Beyond the conventional M1/M2 paradigm of macrophage subpopulations, new subpopulations of macrophages have been recently described in skin and lung biopsies from SSc patients. Notably, single-cell ribonucleic acid sequencing has provided evidence for SPP1+ lung macrophages or FCGR3A+ skin macrophages in SSc. Impaired pro-resolving capacities of macrophages such as efferocytosis, i.e. the ability to phagocyte apoptotic cells, could also participate in the inflammatory and autoimmune features in SSc.SummaryThrough 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.

News (Medical) associated with Romilkimab

05 Feb 2021

·endpts.com

Sanofi flunks Parkinson's Phase II, axes handful of mid-stage programs in Q4 earnings

Biogen isn’t the only one hitting roadblocks in Parkinson’s. Two days after the big biotech revealed in year-end earnings that they cut a Phase II program for the neurodegenerative condition, Sanofi axed their own Phase II Parkinson’s drug in its earnings announcement. The trial failed at the end of January, they said, although they will continue developing the compound, known as venglustat, in a handful of rare diseases. It was one of a small clutch of programs Sanofi axed as Paul Hudson continues to cull the pipeline and pivot the hulking French pharma. Gone is romilkimab, an anti-IL13/IL14 bispecific meant to work similarly to Dupixent. Sanofi did not say they were fully shelving the antibody, but they ended development in systemic scleroderma, the only extant clinical program after they pulled the plug on IPF studies in 2017. Sarclisa, the first approved cancer drug fully developed by Sanofi in a decade, is being pulled from a PD-1 combo effort in lymphoma. And two years after a disappointing asthma study, Sanofi and Regeneron are ceasing to develop their anti-IL33 antibody itepekimab for that indication. However, they just put the drug into a pivotal Phase III for COPD, a potentially major market, with results expected by 2024. The Parkinson’s trial had enrolled patients with GBA mutations, the most common genetically-driven form of the disease. Patients with the mutation build up high levels of a fatty-sugar molecule called glucocerebroside. The drug was supposed to inhibit the production of these molecules in the brain, but despite strong preclinical evidence, did not meet the primary endpoint in a 270-person study. Sanofi, though, will continue to develop the drug for a handful of indications, including polycistic kidney disease, Tay-Sachs, and Gaucher disease.

Antibody

05 Feb 2021

·www.biospace.com

Sanofi Succeeding with Blue-Chip Asset, Dupixent, While Other Programs Fall Away

Over the course of 2020, Sanofi saw significant growth in its specialty care sales primarily driven by its blue-chip asset, Dupixent, as well as an increase in vaccine sales that were driven by demand for differentiated influenza vaccines, the company announced in its year-end financial report. For the year, Dupixent generated €3.5 billion (about $4.2 billion) for Sanofi. Dupixent, which was co-developed with Regeneron, continues to be a significant driver for Sanofi. In its year-end financial report, Sanofi said sales of Dupixent were driven by continued strong demand in atopic dermatitis (AD) in adult and adolescent patients, rapid adoption in children aged 6 to 11 years, and continued uptake in asthma and chronic rhinosinusitis with nasal polyposis. By the end of 2020, Dupixent has become available in 47 different countries with approximately 230,000 patients on therapy, Sanofi said. Earlier this year, during a call ahead of the J.P. Morgan Healthcare conference, Frank Nestle, Sanofi’s chief scientific officer and Global Head of Research, and Dietmar Berger, Sanofi’s chief medical officer and Global Head of Development, predicted 2021 will be a transformative year for the company. Dupixent plays a significant role in that future, they said. Sanofi Chief Executive Officer Paul Hudson touted the company’s progress in 2020, despite some limitations imposed by the COVID-19 pandemic. He noted the continued uptake in Dupixent use across the globe and also pointed to potential approvals in new indications for the monoclonal antibody that inhibits the signaling of the interleukin-4 and interleukin-13 proteins. The company anticipates approval of Dupixent in pediatric asthma this year. Other highlights for Sanofi include multiple acquisitions that are expected to provide the company a strong standing in areas like, immune-oncology, synthetic biology and cell and gene therapy. The company is also aiming for innovations with protein degraders, antibody conjugates, nanobodies and multi-specific antibodies, specifically bi- and tri-specific. Hudson also pointed to its ongoing COVID-19 vaccine development programs. He said clinical trials are expected to begin on its vaccine candidates. Hudson also said the company is making a more immediate contribution to the pandemic fight by providing manufacturing support to BioNTech and Pfizer.” The year-end report wasn’t all positives. Sanofi reported a few setbacks, including a Phase II Parkinson’s disease study with venglustat. Sanofi said the Phase II study of Parkinson’s disease patients with GBA mutations did not meet the primary endpoint at the end of January and the study for this indication was halted. The disclosure is a setback for the company’s plans for venglustat. Ahead of the J.P. Morgan conference, company officials said venglustat had the potential to be a pipeline in a pill. The venglustat safety pro to be favorable and the development moves forward as planned in other Rare Disease indications, the company said. Venglustat is being assessed in other studies, including Phase III programs for GM2 Gangliosidosis and Autosomal Dominant Polycystic Kidney Disease, as well as Phase II studies in Fabry disease and Gaucher disease Type 3. Other programs that will not continue include the anti-IL4/IL13 bispecific mAb Romilkimab, which was in a Phase II study for systemic scleroderma, as well as asthma treatment Itepekimab and lymphoma treatment Isatuximab. Both of those were also in Phase II. Sanofi said it is working to resolve a Complete Response Letter issued by the U.S. Food and Drug Administration during the fourth quarter for sutimlimab, an investigational monoclonal antibody for the treatment of hemolysis in adults with cold agglutinin disease. The CRL was issued due to manufacturing concerns. There were no clinical concerns. Sanofi said it is working with both the FDA and the third-party manufacturer to reach a resolution in a timely manner. Most Read Today

VaccineGene TherapyAntibodyFinancial StatementAcquisition

05 Feb 2021

·www.biospace.com

Sanofi Succeeding with Blue-Chip Asset, Dupixent, While Other Programs Fall Away

Over the course of 2020, Sanofi saw significant growth in its specialty care sales primarily driven by its blue-chip asset, Dupixent, as well as an increase in vaccine sales that were driven by demand for differentiated influenza vaccines, the company announced in its year-end financial report. Over the course of 2020, Sanofi saw significant growth in its specialty care sales primarily driven by its blue-chip asset, Dupixent, as well as an increase in vaccine sales that were driven by demand for differentiated influenza vaccines, the company announced in its year-end financial report . For the year, Dupixent generated €3.5 billion (about $4.2 billion) for Sanofi. Dupixent, which was co-developed with Regeneron, continues to be a significant driver for Sanofi. In its year-end financial report, Sanofi said sales of Dupixent were driven by continued strong demand in atopic dermatitis (AD) in adult and adolescent patients, rapid adoption in children aged 6 to 11 years, and continued uptake in asthma and chronic rhinosinusitis with nasal polyposis. By the end of 2020, Dupixent has become available in 47 different countries with approximately 230,000 patients on therapy, Sanofi said. Earlier this year, during a call ahead of the J.P. Morgan Healthcare conference, Frank Nestle, Sanofi’s chief scientific officer and Global Head of Research, and Dietmar Berger, Sanofi’s chief medical officer and Global Head of Development, predicted 2021 will be a transformative year for the company. Dupixent plays a significant role in that future, they said. Sanofi Chief Executive Officer Paul Hudson touted the company’s progress in 2020, despite some limitations imposed by the COVID-19 pandemic. He noted the continued uptake in Dupixent use across the globe and also pointed to potential approvals in new indications for the monoclonal antibody that inhibits the signaling of the interleukin-4 and interleukin-13 proteins. The company anticipates approval of Dupixent in pediatric asthma this year. Other highlights for Sanofi include multiple acquisitions that are expected to provide the company a strong standing in areas like, immune-oncology, synthetic biology and cell and gene therapy. The company is also aiming for innovations with protein degraders, antibody conjugates, nanobodies and multi-specific antibodies, specifically bi- and tri-specific. Hudson also pointed to its ongoing COVID-19 vaccine development programs. He said clinical trials are expected to begin on its vaccine candidates. Hudson also said the company is making a more immediate contribution to the pandemic fight by providing manufacturing support to BioNTech and Pfizer.” The year-end report wasn’t all positives. Sanofi reported a few setbacks, including a Phase II Parkinson’s disease study with venglustat. Sanofi said the Phase II study of Parkinson’s disease patients with GBA mutations did not meet the primary endpoint at the end of January and the study for this indication was halted. The disclosure is a setback for the company’s plans for venglustat. Ahead of the J.P. Morgan conference, company officials said venglustat had the potential to be a pipeline in a pill. The venglustat safety pro to be favorable and the development moves forward as planned in other Rare Disease indications, the company said. Venglustat is being assessed in other studies, including Phase III programs for GM2 Gangliosidosis and Autosomal Dominant Polycystic Kidney Disease, as well as Phase II studies in Fabry disease and Gaucher disease Type 3. Other programs that will not continue include the anti-IL4/IL13 bispecific mAb Romilkimab, which was in a Phase II study for systemic scleroderma, as well as asthma treatment Itepekimab and lymphoma treatment Isatuximab. Both of those were also in Phase II. Sanofi said it is working to resolve a Complete Response Letter issued by the U.S. Food and Drug Administration during the fourth quarter for sutimlimab, an investigational monoclonal antibody for the treatment of hemolysis in adults with cold agglutinin disease. The CRL was issued due to manufacturing concerns. There were no clinical concerns. Sanofi said it is working with both the FDA and the third-party manufacturer to reach a resolution in a timely manner.

VaccinePhase 2AcquisitionDrug ApprovalClinical Result

100 Deals associated with Romilkimab

External Link

KEGG	Wiki	ATC	Drug Bank
D11598	-	-	DB16318

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Indication	Highest Phase	Country/Location	Organization	Date
Idiopathic Pulmonary Fibrosis	Phase 2	Denmark	Sanofi	01 May 2015
Idiopathic Pulmonary Fibrosis	Phase 2	Greece	Sanofi	01 May 2015
Idiopathic Pulmonary Fibrosis	Phase 2	Canada	Sanofi	01 May 2015
Idiopathic Pulmonary Fibrosis	Phase 2	South Korea	Sanofi	01 May 2015
Idiopathic Pulmonary Fibrosis	Phase 2	United Kingdom	Sanofi	01 May 2015
Idiopathic Pulmonary Fibrosis	Phase 2	Spain	Sanofi	01 May 2015
Idiopathic Pulmonary Fibrosis	Phase 2	Portugal	Sanofi	01 May 2015
Idiopathic Pulmonary Fibrosis	Phase 2	Turkey	Sanofi	01 May 2015
Idiopathic Pulmonary Fibrosis	Phase 2	Czechia	Sanofi	01 May 2015
Idiopathic Pulmonary Fibrosis	Phase 2	Australia	Sanofi	01 May 2015

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02921971 (CTgov)	Phase 2	Scleroderma, Diffuse	97	Placebo (Placebo)	ibdgczfhli(ioeipgxhdt) = alokkkayqg srgetybdxy (rjcjtjyodd, yftzlujxij - wnlxfavdla) View more	-	02 Feb 2022
				SAR156597 (SAR156597)	ibdgczfhli(ioeipgxhdt) = jwbrbeyfsq srgetybdxy (rjcjtjyodd, pmxagphtjq - jpslsomgan) View more
NCT02921971 (Pubmed \| Arthritis Rheumatol \| Ann Rheum Dis) Manual	Phase 2	Scleroderma, Diffuse	97	romilkimab	(pwbjbnlzut) = nxieuffnmt mkdulnpnow (qrfxzhpzow ) View more	Positive	01 Dec 2020
				Placebo	(pwbjbnlzut) = jwlratbcei mkdulnpnow (qrfxzhpzow ) View more
NCT02345070 (ESTAIR, CTgov)	Phase 2	Idiopathic Pulmonary Fibrosis	327	placebo	ywaowxhvyp(osblsuhrhw) = pkypxaknhs onaxuagrcl (qwyshqfphq, lwjvtdyjae - rxzaaiihfn) View more	-	26 May 2020

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