Ilsira (levilimab) / Biocad - LARVOL DELTA

Efficacy and Safety of Levilimab in Combination with Methotrexate in Patients with Active Rheumatoid Arthritis: 56-Week Results of Phase III Randomized Double-Blind Placebo-Controlled Trial SOLAR. (PubMed, Dokl Biochem Biophys) - ": Open label period confirmed the lasting efficacy and safety of levilimab in combination with MTX in subjects with MTX resistant active RA and suggested the possibility of switching to levilimab maintenance regimen (once every 2 weeks) (Q2W) in those who achieved remission of RA at week 24."

Combination therapy • Journal • P3 data • Immunology • Infectious Disease • Inflammatory Arthritis • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Tuberculosis

Efficacy and safety of levilimab in the treatment of patients with rheumatoid arthritis (PubMed, Ter Arkh) - "Levilimab is a highly effective drug for the treatment of patients with highly and moderately active RA and has a favorable tolerability and safety profile."

Journal • Observational data • Immunology • Inflammatory Arthritis • Musculoskeletal Pain • Pain • Rheumatoid Arthritis • Rheumatology • CRP • KRAS

Interleukin-6 blocking agents for treating COVID-19: a living systematic review. (PubMed, Cochrane Database Syst Rev) - "In hospitalized people with COVID-19, results show a beneficial effect of tocilizumab on all-cause mortality in the short term and probably little or no difference in the risk of adverse events compared to standard care alone or placebo. Nevertheless, both tocilizumab and sarilumab probably result in little or no increase in clinical improvement at D28. Evidence for an effect of sarilumab and the other IL-6 blocking agents on critical outcomes is uncertain or very uncertain. Most of the trials included in our review were done before the waves of different variants of concern and before vaccination was rolled out on a large scale. An additional 17 RCTs of IL-6 blocking agents are currently registered with no results yet reported. The number of pending studies and the number of participants planned is low. Consequently, we will not publish further updates of this review."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • IL6

Clinical cases of complicated diverticulitis against the background of severe course COVID-19. Case report (PubMed, Ter Arkh) - "Patients received hormone therapy and were targeted: the first patient twice (tocilizumab on the first day of hospitalization and olokizumab on the 7th day of inpatient treatment). The second patient received levilimab on the 3rd day of his stay in the hospital...Both patients died. Thus, when using targeted therapy for patients with COVID-19, it is necessary to take into account that they may have previously undiagnosed chronic diseases that can cause fatal complications against the background of immunosuppression."

Journal • Gastrointestinal Disorder • Infectious Disease • Inflammatory Bowel Disease • Novel Coronavirus Disease • Obesity • Pain • Respiratory Diseases

A Two-Stage Study of the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics and Immunogenicity of Various Doses of Levilimab When Administered Intravenously and Subcutaneously to Healthy Subjects and Subjects With Active Rheumatoid Arthritis (clinicaltrials.gov) - P3 | N=261 | Active, not recruiting | Sponsor: Biocad

New P3 trial • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

The Use of Janus Kinase Inhibitors and Anti-Interleukin Therapy in the Russian Federation for COVID-19: A Pharmacoepidemiological Study (ISPOR 2023) - " Data from the IQVIA database on actual sales in the public procurement segments (including regional and federal drug benefits), as well as in retail sales segment in the period 2018-2021 were converted into the number of prescribed daily doses (DDDs), with the calculation of pharmacoepidemiological indicators "Frequency of new drug prescriptions", "Cumulative risk of drug prescription", and "Frequency of drug prescription per year" for tocilizumab, olokizumab, levilimab, sarilumab, canakinumab, anakinra, baricitinib, tofacitinib and upadacitinib. Taking into account the expansion of the use of these groups of drugs, careful monitoring of information about their safety is required."

Clinical • Gene Therapies • Infectious Disease • Novel Coronavirus Disease

Systematic Review with Meta-Analysis and Indirect Comparison of Anti-Interleukin Therapy for COVID-19 (ISPOR 2023) - "A meta-analysis of the results of a systematic review demonstrated the effectiveness of tocilizumab and anakinra in relation to the RR of 28-day mortality, as well as the effectiveness of levilimab in relation to the indicator "OR Improvement by day 14 of the disease"."

Retrospective data • Review • Gene Therapies • Infectious Disease • Novel Coronavirus Disease

Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis. (PubMed, Ann Rheum Dis) - "The results of this SLR, together with one SLR on safety of DMARD and one on glucocorticoids, informed the taskforce of the 2022 update of the EULAR recommendations for pharmacological management of RA."

Journal • Review • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • IL6

Levilimab and baricitinib prescribing experience in outpatient COVID-19 patients' treatment (PubMed, Ter Arkh) - "The addition of levilimab or baricitinib to the therapy regimen for coronavirus infection during the outpatient phase has demonstrated a preemptive anti-inflammatory effect and reduced the probability of lung tissue damage progression."

Journal • Cardiovascular • Critical care • Gene Therapies • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Experience of anticipatory therapy with IL-6 receptor inhibitors and perspectives for its use in the evolution of COVID-19 (PubMed, Ter Arkh) - "Results. The analyzed data on clinical efficacy and safety formed the basis of recommendations proposed by experts for the use of levilimab in the inpatient and outpatient medical care for COVID-19."

Journal • Infectious Disease • Novel Coronavirus Disease • IL6

Efficacy and safety of levilimab in combination with methotrexate in patients with active rheumatoid arthritis: 1-year results of phase III, double-blind, placebo-controlled, randomized trial (EULAR 2022) - P3 | "Open label period confirmed the lasting efficacy and safety of levilimab in combination with MTX in subjects with MTX resistant active RA and suggested the possibility of switching to maintenance (Q2W) regimen of levilimab in those who achieved remission of RA at week 24. Trial registration: Clinicaltrials.gov identifier NCT04397562"

Clinical • Combination therapy • P3 data • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Efficacy of Biologics and Targeted Synthetic Drugs Approved in Russia to Treat Adults with Active Rheumatoid Arthritis: A Systematic Review and Network Meta-Analysis (ISPOR 2022) - "We conducted a systematic search for RCTs evaluating the efficacy of biologics (adalimumab, golimumab, levilimab, olokizumab, sarilumab, tocilizumab, infliximab, rituximab, certolizumab pegol, abatacept and etanercept) and tsDMARDs (tofacitinib, baricitinib and upadacitinib), both in combination with conventional synthetic DMARDs (csDMARDs) and in monotherapy for the treatment of adults with active RA...The proportion of patients with an inadequate response to previous methotrexate therapy was at least 50% in the included RCTs...Conclusion. Given the predominantly comparable relative effectiveness of the analyzed drugs, health professionals should also consider other factors, when choosing a treatment option for adults with active RA."

Retrospective data • Review • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

SOLAR: Study of the Efficacy and Safety of BCD-089 in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis (clinicaltrials.gov) - P3 | N=154 | Completed | Sponsor: Biocad | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

SOLAR: Study of the Efficacy and Safety of BCD-089 in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis (clinicaltrials.gov) - P3; N=150; Active, not recruiting; Sponsor: Biocad; Trial completion date: Sep 2023 ➔ May 2022; Trial primary completion date: Sep 2023 ➔ Dec 2021

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

Efficacy and safety of Interleukin-6 receptor monoclonal antibody levilimab in COVID-19 patients: real practice data (APLAR 2021) - "Levilimab administration resulted in favorable course of COVID-19and good tolerability of treatment."

Clinical • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Infectious Disease • Inflammation • Novel Coronavirus Disease • Renal Disease • Respiratory Diseases • IL6 • IL6R

The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study. (PubMed, Inflamm Res) - P3 | "In patients with radiologically confirmed SARS-CoV-2 pneumonia, requiring or not oxygen therapy (but not ventilation) with no signs of other active infection administration of LVL + SOC results in an increase of sustained clinical improvement rate."

Clinical • Journal • P3 data • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • IL6

[VIRTUAL] The first experience of anti-IL6 administration for COVID-19 infection (ERS 2021) - "122 patients were examined, (59 men and 63 women, age 59.63±10.7 years (31-82 years, ZK-S=1.0; p=0.261), CT1 1.6%, CT2 36, 1%, CT3 54.1%, CT4 8.2% after detection received favipiravir 9.8%, umifenovir 31.1% and its combination with alpha interferon 15.8%, glucocorticosteroids 14.8% and antibiotics 59%...On day 12.11±3.12 (ZK-S=1.26; p=0.1) olokizumab was prescribed (72.1%), tocilizumab (23.8%), levilimab (3.3%) and tocilizumab-olokizumab sequentially (0.8%)... Anti-IL-6 drugs, when administered intravenously, are effective in the treatment of COVID-19, and their effectiveness is higher in the initial stages of desaturation."

Infectious Disease • Novel Coronavirus Disease • CRP

[VIRTUAL] THE DYNAMICS OF INFLAMMATORY MARKERS IN COVID-19 PATIENTS TREATED WITH LEVILIMAB (EULAR 2021) - P3 | "The significant differences in the dynamics of ESR, CRP and IL-6 after LVL administration compared to placebo confirmed the pharmacodynamic effect and its potency to prevent the excessive release of inflammatory substances in severely ill COVID-19 patients."

Clinical • Acute Respiratory Distress Syndrome • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Septic Shock • CRP

[VIRTUAL] EFFICACY AND SAFETY OF LEVILIMAB IN COMBINATION WITH METHOTREXATE IN SUBJECTS WITH ACTIVE RHEUMATOID ARTHRITIS: PHASE III, DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED TRIAL (EULAR 2021) - P3 | "The study confirmed superior efficacy of levilimab + MTX over placebo + MTX in subjects with MTX resistant active RA. No new safety signals were detected. Trial registration: Clinicaltrials.gov identifier NCT04397562"

Clinical • Combination therapy • P3 data • Immunology • Infectious Disease • Inflammatory Arthritis • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Tuberculosis

Interleukin-6 blocking agents for treating COVID-19: a living systematic review. (PubMed, Cochrane Database Syst Rev) - "On average, tocilizumab reduces all-cause mortality at D28 compared to standard care alone or placebo and probably results in slightly fewer serious adverse events than standard care alone or placebo. Nevertheless, tocilizumab probably results in little or no increase in the outcome clinical improvement (defined as hospital discharge or improvement measured by trialist-defined scales) at D28. The impact of tocilizumab on other outcomes is uncertain or very uncertain. With the data available, we were not able to explore heterogeneity. Individual patient data meta-analyses are needed to be able to identify which patients are more likely to benefit from this treatment. Evidence for an effect of sarilumab is uncertain and evidence for other anti-IL6 agents is unavailable. Thirty-nine RCTs of IL-6 blocking agents with no results are currently registered, of which nine are completed and seven trials were terminated with no results available. The findings of this review will be..."

Journal • Review • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • IL6

Antibodies to watch in 2021. (PubMed, MAbs) - "Remarkably, by late November 2020, two anti-SARS-CoV antibody products, bamlanivimab and the casirivimab and imdevimab cocktail, were authorized for emergency use by the US Food and Drug Administration (FDA) and the repurposed antibodies levilimab and itolizumab had been registered for emergency use as treatments for COVID-19 in Russia and India, respectively. Despite the pandemic, 10 antibody therapeutics had been granted the first approval in the US or EU in 2020, as of November, and 2 more (tanezumab and margetuximab) may be granted approvals in December 2020.* In addition, prolgolimab and olokizumab had been granted first approvals in Russia and cetuximab saratolacan sodium was first approved in Japan...Based on the information publicly available as of November 2020, 44 antibody therapeutics are in late-stage clinical studies for non-cancer indications, including 6 for COVID-19, and marketing applications for at least 6 (leronlimab, tezepelumab, faricimab,..."

Journal • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases

SOLAR: Study of the Efficacy and Safety of BCD-089 in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis (clinicaltrials.gov) - P3; N=150; Active, not recruiting; Sponsor: Biocad; Recruiting ➔ Active, not recruiting

Clinical • Combination therapy • Enrollment closed • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

A Clinical Trial of the Efficacy and Safety of Levilimab (BCD-089) in Patients With Severe COVID-19 (clinicaltrials.gov) - P3; N=206; Completed; Sponsor: Biocad; Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • IL6

Favipiravir permanently registered in Russia for COVID-19 treatment (TASS) - "Favipiravir, a drug used to treat COVID-19, has received permanent registration in Russia, Russian Deputy Health Minister Viktor Fisenko said....'Following a sped-up procedure, we have greenlit circulation of prevention drugs (vaccines), antiviral therapy drugs - Favipiravir, Remdesivir, and a drug used to mitigate a cytokine storm - Levilimab,' he said, adding that Favipiravir has received a permanent registration certificate. Earlier, the Russian Federal Service for Surveillance in Healthcare informed that Russia had registered three drugs based on Favipiravir: Avifavir, Areplivir and Coronavir."

Cytokine storm • Non-US regulatory • Infectious Disease • Novel Coronavirus Disease

The Russian Ministry of Health has released version 8 of the guidelines for coronavirus [Google translation] (Ministry of Health of the Russian Federation) - "The Ministry approved a new - 8 version of the Interim Recommendations for the Prevention, Diagnosis and Treatment of the New Coronavirus Infection COVID-19....The treatment regimen included a new Russian drug for systemic anti-inflammatory therapy - Levilimab....The drugs lopinavir and ritonavir were excluded from the recommendations as they did not show sufficient effectiveness in the treatment of COVID-19....Hydroxychloroquine has remained in treatment regimens for patients with mild to moderate disease....The new section describes the indications and contraindications for the use of the vaccine, as well as a list of priority groups for priority vaccination."

Clinical guideline • Infectious Disease • Novel Coronavirus Disease