| Developers: | Biocad |
| Last Release Date: | 2021/06/30 |
| Branches: | Pharmaceuticals, Medicine, Healthcare |
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The original drug levilimab (INN) is a domestic inhibitor of interleukin-6.
2021
470,000 patients cured thanks to levilimab
Almost half a million patients diagnosed with COVID-19 were cured thanks to the Russian drug. Biocad announced this on April 19, 2022.
According to IQVIA analytics, the use of original Russian genetically engineered biological drugs in 2021 increased by 450%. In 2021, 470 thousand patients who were diagnosed with coronavirus received levilimab therapy.
The data obtained during the clinical trial of the drug in patients with coronavirus became the basis for its inclusion in the methodological recommendations of the Ministry of Health of the Russian Federation. Over the two years of use of levilimab, successful experience has been accumulated in combating hyperinflammation, which in some cases accompanies the development of a new coronavirus infection. As of April 2022, levilimab is the leader in the class of interleukin 6 receptor inhibitors (i-IL6R) in Russia and is used in the vast majority of patients hospitalized with a diagnosis of COVID-19.
In Jul 2021, levilimab was also approved for rheumatoid arthritis. By mid-April 2022, the drug has already been prescribed to more than 300 patients with such a diagnosis. Biocad recalled that according to unofficial data, about 770 thousand patients with rheumatoid arthritis are sick in Russia, about 320 thousand people are registered at the dispensary. On average, 30% of patients with diagnosed rheumatoid arthritis need therapy with genetically engineered biological drugs, while in fact the drug is received no more than 6%.
 | Registration of levilimab for rheumatoid arthritis took place in the context of the COVID-19 pandemic, when there were great concerns about immunosuppressive therapy. However, the experience gained by this time in the real clinical practice of COVID-19 therapy has demonstrated the effectiveness and safety of the drug. This made it possible to extrapolate the obtained data to the population of patients with rheumatoid arthritis and with greater confidence consider levilimab as one of the most priority approaches in the treatment of this complex category of patients, "said Doctor of Medical Sciences, Professor Galina Lukina, Head of the Research Department of Rheumatology of the Moscow Clinical Research Center named after A.S. Loginova DZM. |  |
According to IQVIA, the Russian pharmaceutical market in 2021 showed an increase of 13% compared to 2020 and reached 2 trillion rubles. 98% of genetically engineered biological drugs (GEBDs) for the treatment of autoimmune diseases are sold through the public procurement segment. GEBDs for the treatment of autoimmune diseases are mainly represented by original drugs and biosimilars.
Publication of research in the journal Inflammation Research
The results of a clinical trial of the drug with INN - levilimab in the scientificallymedical peer-reviewed journal Inflammation Research () have been published Switzerland. This was announced on October 6, 2021 by the company. The Biocad study confirmed the efficacy and safety of the use of an original interleukin-6 receptor inhibitor for the treatment of patients with severe forms who do not COVID-19 require mechanical ventilation. The CORONA trial was a Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trial. The study is registered with the National Institute. health care USA
The results of the study confirmed that in patients diagnosed with SARS-CoV-2 pneumonia that does not require invasive ventilation, without signs of another active infection, the use of levilimab together with standard treatment leads to an increase in the frequency of persistent clinical improvement. 63.1% and 42.7% of patients in the single subcutaneous dose groups of levilimab 324 mg and placebo, respectively, achieved sustained clinical improvement on Day 14.
In addition, the study found that, starting on Day 13, a significantly higher number of patients who received levilimab at a single dose of 324 mg were discharged from the hospital (53.9%) compared with the placebo group (39.1%).
It was also demonstrated that in the levilimab group, starting from day 5, fewer patients required oxygen therapy, and the proportion of patients requiring transfer to the intensive care unit after a single administration of levilimab 324 mg was significantly less (2.9%) compared with placebo (9.7%).
The incidence of adverse reactions was comparable between groups.
The study involved 217 patients, men and non-pregnant women aged 18 years and older, hospitalized due to the severe course of pneumonia caused by COVID-19. 206 of them were randomly selected for single subcutaneous administration of 324 mg or placebo, which were administered to patients in combination with standard treatment. 204 patients received the prescribed therapy. The efficacy parameter was the proportion of patients with sustained clinical improvement on Day 14.
| | The natural course of COVID-19 in most cases is a mild or medium-severe disease that causes a limited immune response, "said Yulia Linkova, director of the clinical development department of the biotechnological company BIOCAD. - However, in about 20% of cases, COVID-19 can progress to a severe disease caused by an excessive immune response - massive release of pro-inflammatory cytokines ('cytokine storm'), which is accompanied by lung damage, the development of acute respiratory distress syndrome, multiple organ failure and impaired blood clotting. Cytokine storm is associated with disease severity and adverse outcome. The need to find an effective therapy to suppress the cytokine storm was a prerequisite for a clinical study aimed at studying the effectiveness of inhibiting the interleukin-6 signaling pathway in patients with severe COVID-19. | |
The CORONA study was conducted at 12 sites in the Russian Federation in accordance with the Helsinki Declaration and Good Clinical Practice standards.
Approval of the medicine "Ilsira" by the Russian Ministry of Health for treatment of rheumatoid arthritis
The Ministry of Health of the Russian Federation approved the use of Ilsira (levilimab) for the treatment of rheumatoid arthritis (RA), expanding the current list of indications. This was announced on June 30, 2021 by the biotechnological company Biocad.
Levilimab is a monoclonal antibody against the interleukin-6 receptor (iIL-6p) is an original development of the Russian company Biocad. From the idea of creating a drug, early development, preclinical and clinical studies to release, 10 years have passed. The full production cycle is carried out in Russia.
The clinical development program and the possibility of further clinical use of the drug with INN - levilimab for the therapy of rheumatoid arthritis were considered at a meeting of the relevant commission of the Expert Council of the Ministry of Health of the Russian Federation in the specialty "rheumatology" on May 29, 2021. The relevant commission of the Expert Council decided: "after the approval of the Ministry of Health of Russia, the indication of" rheumatoid arthritis "for levilimab to consider its inclusion in clinical recommendations."
| | "Rheumatoid arthritis is a systemic autoimmune disease, 3 times more common in women than in men. The peak incidence occurs at the able-bodied socio-active age (35-55 years), and, with untimely prescription of biological therapy, leads to early disability. As of June 2021, the provision of patients with rheumatoid arthritis with genetically engineered biological drugs (GEBD) does not exceed 5.6%. The drug is an original interleukin-6 receptor inhibitor (iIL-6p), which, when promptly prescribed, suspends the progression of rheumatoid arthritis, which avoids disability, "said Dmitry Sivokoz, Deputy General Director for Marketing, Sales and Market Access Biotech Company Biocad. | |
Up to 30% of patients with a confirmed diagnosis of rheumatoid arthritis need GEBD due to the inefficiency of other treatments.
Clinical studies of a drug for the treatment of rheumatoid arthritis
On May 31, 2021, the biotechnological company BIOCAD presented the results of a clinical study of the efficacy and safety of the Russian original monoclonal antibody to the interleukin receptor - 6 (IL-6R) in patients with active rheumatoid arthritis (AURORA). Levilimab in combination with methotrexate, used in two regimens - once or twice a week, has demonstrated clinical efficacy along with a favorable safety profile, which is the basis for further study of levilimab in the phase III study.
According to the company, an international, multicenter, randomized, double-blind, placebo-controlled, AURORA phase II clinical trial was conducted in 19 clinical centers in Russia and the Republic of Belarus in accordance with the Helsinki Declaration of the World Medical Association and the requirements of Good Clinical Practice (GCP). The study included patients diagnosed with active rheumatoid arthritis according to the ACR (American College of Rheumatology) criteria. The study evaluated the efficacy of therapy for 52 weeks, safety for 56 weeks, immunogenicity, as well as pharmacokinetic and pharmacodynamic parameters.
| | Efficacy analysis showed that subcutaneous administration of levilimab in combination with methotrexate demonstrated the superiority of this drug over placebo in combination with methotrexate. At Week 12 of the study, 77% and 57% of patients in the levilimab 162 mg QW and QW groups achieved ACR20 response, respectively, and 17% in the placebo group. The dynamics of pharmacodynamic markers (concentration of soluble receptor to IL-6, C-reactive protein) indicated effective suppression of the inflammatory process in patients with active rheumatoid arthritis. During the study, it was noted that more frequent administration of levilimab - 1 times a week - showed a trend towards higher efficacy compared to the regimen 1 times 2 weeks. stated in study report | |
Levilimab is an original monoclonal antibody against the interleukin-6 receptor, the full production cycle of the drug, including the synthesis of a molecule of the active ingredient, is carried out in the Russian Federation. Levilimab affects both forms of IL-6 receptors: membrane and soluble, thereby firmly blocking the pro-inflammatory cascade, which plays a key role in the pathogenesis of rheumatoid arthritis. Ilsira was approved in June 2020 for the indication "Pathogenetic therapy of cytokine release syndrome in severe coronavirus infection (COVID-19)" and as of May 2021 is used to treat the complicated course of COVID-19. Documents for registration of the indication of rheumatoid arthritis are submitted to the Ministry of Health, registration of the indication will expand the possibilities of providing patients with rheumatoid arthritis with highly effective therapy.
2020
Inclusion in the list of vital and essential medicinal products
In accordance with the order of the Government of the Russian Federation of October 12, 2020 No. 2626-r, levilimab, a drug manufactured by the biotechnological company Biocad, is included in the list of vital and essential drugs. Biocad announced this on October 15, 2020. Levilimab is intended for patients with a moderate course of coronavirus infection as a proactive therapy until the development of a life-threatening state associated with cytokine release syndrome.
Levilimab is a monoclonal antibody that blocks the interleukin-6 receptor (IL-6R), which plays a key role in the pathological process in COVID-19. Getting coronavirus into the body mobilizes the protective mechanisms of the immune system to fight the disease. However, in some people, an excessive activation of the immune response occurs with an uncontrolled release of proteins (cytokines), as a result of which a so-called cytokine storm develops, which can lead to damage to the patient's lungs, kidneys and heart. Levilimab helps to prevent an inadequate immune response of the body and thereby smooths out the devastating consequences of fighting infection.
Initially, levilimab was developed for the treatment of rheumatoid arthritis, but with the onset of the COVID-19 pandemic, it was decided to expand the program of clinical trials of the third phase to obtain additional data on the effectiveness and safety of the drug in coronavirus infection.
At the end of September, the regulation of the Ministry of Health made it possible to include drugs used to treat coronavirus infection in the list of vital and essential drugs according to an accelerated scheme.
{{quote "The inclusion of levilimab in the list of vital and essential drugs provides additional treatment opportunities for doctors, and will also make COVID-19 therapy more accessible to patients. Patients will be able to receive drug therapy with levilimab free of charge when hospitalized in the compulsory medical insurance channel, and at the expense of regional benefits, - commented Dmitry Morozov, General Director of the biotechnological company BIOCAD. }}
Introduction into the guidelines of the Ministry of Health
On September 3, 2020 Ministry of Health of the Russian Federation COVID-19 , a domestic original drug with the trade name Ilsira (INN - levilimab) was included in the guidelines for therapy. The drug is developed in a biotechnology company BIOCAD and is used to prevent a cytokine storm, one of the worst complications in coronavirus infection. Biocad announced this on September 4, 2020.
Levilimab is a monoclonal antibody that blocks the interleukin-6 receptor (IL-6R), which plays a key role in the pathological process in COVID-19.
Getting coronavirus into the body mobilizes the protective mechanisms of the immune system to fight the disease. However, in some people, an excessive activation of the immune response occurs with an uncontrolled release of proteins (cytokines), as a result of which a so-called cytokine storm develops, which can lead to damage to the patient's lungs, kidneys and heart. Levilimab helps to prevent an inadequate immune response of the body and thereby smooths out the devastating consequences of fighting infection. The drug is intended for patients with a moderate course of coronavirus infection with a risk of developing cytokine release syndrome. Initially, levilimab was developed for the treatment of rheumatoid arthritis, but with the onset of the COVID-19 pandemic, it was decided to expand the program of clinical trials of the third phase to obtain additional data on the effectiveness and safety of the drug in coronavirus infection.
| | It is expected that the use of levilimab at the very beginning of clinical manifestations of respiratory failure will prevent the transfer of patients to the intensive care unit. The therapeutic effect with injectable use occurs in the next 24 hours, reaching the maximum effect in an average of 96 hours. The inclusion of our drug in the guidelines of the Ministry of Health will allow the most vulnerable groups of patients to receive help en masse, - said Dmitry Morozov, General Director of BIOCAD. | |
Patients receive drug therapy with levilimab when hospitalized free of charge, according to the compulsory medical insurance program. Levilimab is administered once in the form of two subcutaneous injections in a total dose of 324 mg (2 syringes of 162 mg).
The clinical trial of the third phase of the drug in COVID-19 includes 204 patients. Such institutions as the Central Clinical Hospital of the Office of the President of the Russian Federation, Bashkir State Medical University, City Clinical Hospital No. 40 of the Moscow Department of Health, the Republican Clinical Hospital of Dagestan and other institutions appear as centers where the study takes place.
The marketing authorization for the drug with INN levilimab was issued by the Ministry of Health in early June 2020. The drug is included in the guidelines, which should ensure the mass use of levilimab therapy in all regions of Russia.
BIOCAD for September 2020 is working on the development of a vaccine against COVID-19. The company takes part in studies of several vaccines at once, two of which are recognized by the World Health Organization (WHO) as promising.
Registration of the drug in Russia under the Ilsira trademark
On June 6, 2020, the Ministry of Health of Russia announced the registration of the second drug for the treatment of coronavirus COVID-19. The medicine is called "Levilimab" (trade name "Ilsira"). It is produced by the biotech company Biocad.
It is indicated for use in patients with severe disease. In particular, when a person has an excessive inflammatory reaction of the body to the virus, which leads to damage to the lung tissue and not only, the Ministry of Health said in a statement.
The drug is indicated in patients with a severe course of the disease, when the so-called cytokine storm develops, the prevention of the development of which is extremely important in the treatment of COVID-19, noted in the department.
Levilimab was originally developed as a drug for rheumatoid arthritis, but it also showed results in the fight against coronavirus.[1]
By June 8, 2020, the drug is undergoing the third phase of clinical trials to confirm its effectiveness precisely for complications of coronavirus infection. The study involves 13 medical centers that note positive dynamics in patients with moderate disease. If positive results are received, the tool will receive a permanent registration certificate.
According to Dmitry Morozov, General Director of Biocad, Levilimab is intended for subcutaneous administration. There are two syringes in the pack. Doctors either put them to the patient at the same time, or with a certain delay. And after that, the person leaves for observation. As a rule, after 10 days the patient is discharged, Morozov added.
| | This is a completely original development. The molecules are made in our company, this is not a copy, not a generic or analogue. This is an original drug, original molecules, - he stressed. | |
Conducting clinical trials of the product
As of May 12, 2020, the Ministry of Health of the Russian Federation approved clinical trials of the Russian drug with INN-levilimab in 11 medical centers. Doctors note the positive dynamics of patients with confirmed moderate to severe coronavirus. Registration of the drug in the Ministry of Health of the Russian Federation is expected at the end of May 2020. This was reported on May 12, 2020 in BIOCAD. To confirm the effectiveness of the drug, it is with coronavirus infection that the company begins organizing phase 3 clinical trials.
According to Nikita Lomakin, chief investigator of the Central Clinical Hospital of the Office of the President of the Russian Federation, a positive and almost unique feature of the clinical trial protocol is that patients of moderate and severe severity of the disease with the first clinical signs of respiratory failure are involved in the study.
| | "Not only a new molecule for COVID infection, but a fundamentally different approach to managing these patients compared to the current recommendations does not stop, but prevents the development of a cytokine storm. At the same time, based on the experience of our center, it seems that the main predictor of its development is not the laboratory, but the clinical course of the disease. The prescription of levilimab at the very beginning of the clinical manifestation of respiratory failure prevents the transfer of patients to the intensive care unit. Of the 36 patients, 10 were discharged from the hospital on day 7-8, 1 patient was transferred to intensive care, " noted' Nikita Lomakin, Principal Investigator of the Central Design Bureau of the Office of the President of the Russian Federation | |
As of May 12, 2020, such medical centers have joined the clinical trials of the drug with INN levilimab, as the Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University," State Health Institution of the City of Moscow "City Clinical Hospital No. 15 named after O.M. Filatov" of the Department of Health of the city of Moscow, The Ministry of Health of the Russian Federation, it is planned that in the near future North Caucasian centers will join the project after obtaining accreditation, such as the State Budgetary Institution of the Republic of Dagestan "Republican Clinical Hospital," GBU "Republican Clinical Hospital named after Sh. Sh. Ependiev" (Republic of Chechnya) and others.
| | "Within one day only - on May 7, a few days after the publication of the imminent start of clinical trials of the levilimab inhibitor, seven medical centers expressed their desire to take part in the trials. Such high trust in the domestic drug by specialists for us is, among other things, an indicator that we have chosen the right strategy and our drug can significantly help people with complications from coronavirus in the near future. " | |
Levilimab testing plan for COVID-19 therapy
On April 27, 2020, it became known that Levilimab at the end of May could receive registration under a special procedure approved by Decree Governments of the Russian Federation of 03.04.2020 No. 441, and will be tested for therapy from. COVID-19 The company Biocad received permission to conduct a clinical study of the efficacy and safety of levilimab in patients with severe coronavirus infection. Ministry of Health
As reported, according to the Interim Methodological Recommendations for the Prevention, Diagnosis and Treatment of COVID-19, prepared by the Ministry of Health of the Russian Federation, studies conducted in the world prove that mortality in COVID-19 is associated, among other things, with an increase in interleukin-6 levels. The findings prompted the initiation of studies of the effectiveness of interleukin-6 signaling pathway inhibitors in the treatment of severe and critical pneumonia in COVID-19. A month ago, the US government issued a grant for a clinical trial of the American inhibitor tocilizumab (originally registered for use in rheumatoid arthritis in the United States) in patients with COVID-19. Levilimab can become a similar domestic remedy for coronavirus.
According to the World Health Organization, the main cause of death in COVID-19 is acute respiratory distress syndrome, the cause of which is secondary hemophagocytic lymphohistiocytosis of the lungs - an excessive response of the immune system to infection with coronavirus, combined with a rapidly developing fatal cytokine storm (a potentially lethal reaction of the immune system).
| | The use of modern genetically engineered biological drugs, to which levilimab belongs, can avoid severe forms of COVID-19 disease: the timely start of such therapy will reduce the level of hospitalization and mortality of our citizens, reduce the level of burden on the healthcare system, and most importantly, save thousands of lives. The first tests of the interleukin-6 inhibitor as a therapy against coronavirus began to be carried out in the United States, a logical step to strengthen national security should be research on a domestic drug in Russia. | |
Levilimab, originally developed for the treatment of rheumatoid arthritis and proven to be effective in phases 1 and 2 of a clinical trial, may receive accelerated state registration due to the fact that its mechanism of action is associated with a cytokine storm. At the same time, to confirm its effectiveness precisely in coronavirus infection, the company will conduct clinical studies of phase 3.
Taking into account the COVID-19 epidemic, the available data on the high efficiency of inhibition of the interleukin-6 signaling pathway in the treatment of a complicated course of infection, and due to the expected increase in the number of patients, including severe forms of COVID-19, a reduced clinical development program is planned using adaptive design and previously obtained data on pharmacokinetics and pharmacodynamics of the drug. In the context of the developing epidemic, the availability of a domestic drug that prevents or stops the development of severe complications may reduce the mortality associated with COVID-19.
2016: Start of clinical trials of levilimab
rheumatoid arthritis Biocad The company began clinical trials of the drug levilimab in patients with the company in 2016.
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