gimsilumab (KIN-1901) / Roivant, Eisai - LARVOL DELTA

COVID-19 management in patients with comorbid conditions. (PubMed, World J Virol) - "Antiviral agents like Remdesivir, an adenosine nucleotide analog, inhibit viral RNA polymerase and have shown efficacy in reducing COVID-19 severity, leading to its emergency use authorization for hospitalized patients. Other antivirals like ritonavir, lopinavir, and umifenovir disrupt viral replication and entry, but their effectiveness against SARS-CoV-2 remains under investigation. Dexamethasone, a corticosteroid, has been used in critically ill COVID-19 patients to reduce inflammation and prevent respiratory failure, as shown in the RECOVERY trial. Other immunosuppressants like ruxolitinib, baricitinib, and colchicine help modulate the immune response, reducing cytokine storms and inflammation-related complications...Systematic reviews of clinical studies revealed that hydroxychloroquine with or without azithromycin did not decrease viral load nor reduce the severity of symptoms, but increased mortality among acutely hospitalized patients...Monoclonal antibodies like..."

Journal • Review • Acute Lung Injury • Acute Respiratory Distress Syndrome • Cardiovascular • Chronic Kidney Disease • Chronic Obstructive Pulmonary Disease • Diabetes • Ebola Virus Disease • Genetic Disorders • Heart Failure • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Nephrology • Novel Coronavirus Disease • Obesity • Pulmonary Disease • Renal Disease • Respiratory Diseases

Erratum: Anti-Granulocyte-Macrophage Colony-Stimulating Factor Monoclonal Antibody Gimsilumab for COVID-19 Pneumonia: A Randomized, Double-Blind, Placebo-controlled Trial. (PubMed, Am J Respir Crit Care Med) - No abstract available

Clinical • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Anti-GM-CSF Monoclonal Antibody Gimsilumab for COVID-19 Pneumonia: A Randomized, Double-Blind, Placebo-Controlled Trial. (PubMed, Am J Respir Crit Care Med) - P2 | "Gimsilumab did not improve mortality or other key clinical outcomes in patients with COVID-19 pneumonia and evidence of systemic inflammation. The utility of anti-GM-CSF therapy for COVID-19 remains unclear. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). Clinical trial registration available at www."

Clinical • Journal • Acute Respiratory Distress Syndrome • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • CSF2

[VIRTUAL] Anti-GM-CSF Monoclonal Antibody Gimsilumab Improved Ventilator-Free Survival, Decreased Hospitalization Length, and Prevented NT-proBNP Rise in Invasively Ventilated Patients With Hyperinflammatory COVID-19 Pneumonia: A Subgroup Analysis From the Breathe Trial Suggests Neurohormonal Role for . (AHA 2021) - P2 | "GM-CSF inhibition may be therapeutic in ventilated COVID-19 patients through a neurohormonal mechanism. More studies are needed to assess the role of GM-CSF in COVID-19-associated cardiomyopathy, volume status, and ARDS."

Clinical • Acute Respiratory Distress Syndrome • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • CSF2

Pharmaco-Immunomodulatory Therapy in COVID-19. (PubMed, Drugs) - "Specific immune modulators include anti-cytokines such as interleukin (IL)-1 and IL-6 receptor antagonists (e.g. anakinra, tocilizumab, sarilumab, siltuximab), Janus kinase (JAK) inhibitors (e.g. baricitinib, ruxolitinib), anti-tumor necrosis factor-α (e.g. adalimumab, infliximab), granulocyte-macrophage colony-stimulating factors (e.g. gimsilumab, lenzilumab, namilumab), and convalescent plasma, with promising to negative trials and other data. Non-specific immune modulators include human immunoglobulin, corticosteroids such as dexamethasone, interferons, statins, angiotensin pathway modulators, macrolides (e.g. azithromycin, clarithromycin), hydroxychloroquine and chloroquine, colchicine, and prostaglandin D2 modulators such as ramatroban...Research efforts should focus not only on the most relevant immunomodulatory strategies but also on the optimal timing of such interventions to maximize therapeutic outcomes. In this review, we discuss the potential role and safety..."

Journal • Review • Immune Modulation • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease

Repurposed Drugs, Molecular Vaccines, Immune-Modulators, and Nanotherapeutics to Treat and Prevent COVID-19 Associated with SARS-CoV-2, a Deadly Nanovector. (PubMed, Adv Ther (Weinh)) - "Many emerging nanotechnology-based interventions will be critical in the fight against the deadly virus by facilitating early detection and enabling target oriented multidrug therapeutics. The therapeutic candidates discussed in this article include remdesivir, dexamethasone, hydroxychloroquine, favilavir, lopinavir/ritonavir, antibody therapeutics like gimsilumab and TJM2, anti-viral nanoparticles, and nanoparticle-based DNA and mRNA vaccines."

Journal • Review • Immune Modulation • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

Targeting GM-CSF in COVID-19 Pneumonia: Rationale and Strategies. (PubMed, Front Immunol) - "Initial findings from patients with COVID-19 treated with a single intravenous dose of mavrilimumab, a monoclonal antibody binding GM-CSF receptor α, showed oxygenation improvement and shorter hospitalization. Anti-GM-CSF monoclonal antibodies, TJ003234 and gimsilumab, will be tested in clinical trials in patients with COVID-19, while lenzilumab received FDA approval for compassionate use. These trials will help inform whether blunting the inflammatory signaling provided by the GM-CSF axis in COVID-19 is beneficial."

Journal • Review • Immune Modulation • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

A Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome Secondary to COVID-19 (BREATHE). (clinicaltrials.gov) - P2; N=270; Recruiting; Sponsor: Kinevant Sciences GmbH; Trial completion date: Oct 2020 ➔ Mar 2021; Trial primary completion date: Jul 2020 ➔ Oct 2020

Clinical • Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome Secondary to COVID-19 (BREATHE) (clinicaltrials.gov) - P2; N=227; Completed; Sponsor: Kinevant Sciences GmbH; Active, not recruiting ➔ Completed

Trial completion • Acute Lung Injury • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Phase 1 Study With KIN-1901 in Healthy Subjects and Subjects With Ankylosing Spondylitis (clinicaltrials.gov) - P1; N=36; Completed; Sponsor: Kinevant Sciences GmbH; Active, not recruiting ➔ Completed; Trial completion date: Dec 2020 ➔ Apr 2020; Trial primary completion date: Dec 2020 ➔ Apr 2020

Clinical • Trial completion • Trial completion date • Trial primary completion date • Ankylosing Spondylitis • Rheumatology

A Study to Assess the Efficacy and Safety of of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome Secondary to COVID-19. (clinicaltrials.gov) - P2; N=270; Recruiting; Sponsor: Kinevant Sciences GmbH

Clinical • New P2 trial • Acute Respiratory Distress Syndrome • Novel Coronavirus Disease • Respiratory Diseases

Phase 1 Study With KIN-1901 in Healthy Subjects and Subjects With Ankylosing Spondylitis (clinicaltrials.gov) - P1; N=46; Recruiting; Sponsor: Kinevant Sciences GmbH

Clinical • New P1 trial • Ankylosing Spondylitis • Pain • Rheumatology

A Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome Secondary to COVID-19 (BREATHE) (clinicaltrials.gov) - P2; N=227; Active, not recruiting; Sponsor: Kinevant Sciences GmbH; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Acute Lung Injury • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Altasciences completes phase I study on gimsilumab for ARDS in Covid-19 (GlobeNewswire, ALTASCIENCES Company Inc.) - "Altasciences has completed a Phase I study for the development of gimsilumab...found to be up-regulated in SARS CoV-2 in patients with or at risk of developing acute respiratory distress syndrome (ARDS)....'We are proud to have collaborated with Roivant Sciences on this important development, which may help ease the suffering of patients afflicted by COVID-19'."

Licensing / partnership • Trial completion • Acute Respiratory Distress Syndrome • Novel Coronavirus Disease • Respiratory Diseases

Phase 1 Study With KIN-1901 in Healthy Subjects and Subjects With Ankylosing Spondylitis (clinicaltrials.gov) - P1; N=36; Active, not recruiting; Sponsor: Kinevant Sciences GmbH; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Ankylosing Spondylitis • Rheumatology

Temple treats 1st patient in US in trial of gimsilumab for patients with COVID-19 and ARDS (Eurekalert) - "'Emerging evidence suggests that GM-CSF may contribute to clinical worsening in COVID-19,' Dr. Criner said. 'We are proud to participate in this clinical trial testing gimsilumab in this vulnerable patient population.'....The multi-site clinical trial will enroll up to 270 patients with a confirmed diagnosis of COVID-19 and clinical evidence of acute lung injury or ARDS. Subjects will be randomized 1:1 to receive either gimsilumab or placebo. The primary endpoint of the study is incidence of mortality by Day 43."

Media quote

Roivant provides updates for pivotal BREATHE clinical trial evaluating gimsilumab in Covid-19 patients for the prevention and treatment of acute respiratory distress syndrome (PRNewswire) - "Roivant Sciences today announced several updates for...pivotal BREATHE trial evaluating the impact of intravenous (IV) treatment with gimsilumab on mortality in COVID-19 patients with lung injury or ARDS. The independent Data Monitoring Committee (DMC) for BREATHE unanimously recommended that the trial continue after a pre-specified safety assessment evaluating data from the first 10% of randomized subjects after six days of follow-up....Roivant recently amended the protocol to permit the use of investigational antivirals (e.g. remdesivir) during the study, as well as treatment with convalescent plasma prior to enrollment. 56 patients have been enrolled in the study to date, and a total of 7 sites have been initiated..."

Clinical protocol • Cytokine storm • DSMB • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Newly added product (Bioworld) - Preclinical, Novel Coronavirus Disease

Pipeline update