Regulator approves first trial of lab-grown antibody drug
Tocilizumab won the green light because of its ability to lower aberrant host immune response that leads to an inflammatory cytokine storm -- an overreaction of the immune system -- and death in hospitalised patients.
The Central Drugs Standard Control Organisation (CDSCO) on Sunday approved the first multi-centric trial of Tocilizumab in India after the second-line drug to treat rheumatoid arthritis emerged as a treatment option for the coronavirus disease (Covid-19).
Tocilizumab won the green light because of its ability to lower aberrant host immune response that leads to an inflammatory cytokine storm -- an overreaction of the immune system -- and death in hospitalised patients.
Tocilizumab is a monoclonal antibody that acts against interleukin-6 (IL-6), a chemical that causes inflammation. “The deterioration in the Covid-19 patients’ condition in the majority of cases is due to hyper-immunity, or an excessive response of one’s own immune system. This cytokine storm or Cytokine Release Syndrome (CRS) is caused by the release of inflammatory chemicals in the body namely IL-6, TNF-alpha and IL1 among others. Tocilizumab is an antibody against IL-6, which is already available, licenced and effective in treating CRS caused by other conditions,” Dr A S Soin, chairman of the Medanta Liver Transplant Institute, Medanta-The Medicity, Gurugram.
Dr Soin is the national lead investigator for the randomised control trial for the use of Tocilizumab in Covid-19 in India. The trial will be conducted in several hospitals in Delhi-National Capital Region, Haryana, Maharashtra, Uttar Pradesh, Telangana and Tamil Nadu.
Monoclonal antibodies are lab-made proteins that act like natural antibodies and that work by identifying and binding to the virus to destroy it. They have been able to block coronavirus infection in labs in the Netherlands and Israel and are emerging as a critical new tool against Covid-19, which has infected 4 million people and killed at least 280,000 since December 219.
The antiviral remedesvir is the only drug that has been approved for emergency use to treat Covid-19 by the US Food and Drug Administration. In the absence of a vaccine or drug to treat Covid-19, clinicians are relying on repurposing existing drugs to identify a therapy that is both safe and effective.
“The indications are very strong that its use early in the course of Covid-19 infection will mitigate CRS and prevent patients from going into the full blown syndrome and progression to acute respiratory syndrome needing ICU admission and ventilation, multi-organ dysfunction, and death,” said Dr Soin.
Inflammatory cytokine storm stops oxygenation by impeding gas exchange in the lungs, leading to death. “Our research has identified that pathogenic T cells and inflammatory monocytes incite inflammatory storm with large amount of interleukin-6, therefore monoclonal antibody that targets the IL-6 pathways may potentially curb inflammatory storm. Tocilizumab treatment that {involves} blocking IL-6 receptors showed inspiring clinical results including temperature {that} returned to normal quickly and respiratory function. Tocilizumab is an effective treatment in severe patients of Covid-19 to calm the inflammatory storm and reduce mortality,” according to a study from China published in the Journal of Translational Medicine on April 14.
“Tocilizumab is undergoing clinical trials in many countries, where the treatment protocols include severely ill patients who may be too sick to respond to treatment. In India, the majority of hospitalized patients have moderate illness that doesn’t need ICU or ventilator support, and the idea is to prevent them from progressing to the severe stage,” said Dr Soin.
“As soon as we reboot, the infection rates will surge. We eagerly await the results of this trial. If it works, it could save thousands in India and have a real global impact,” said Dr Naresh Trehan, chairman, Medanta-The Medicity which was the first private hospital to admit Covid-19 patients in India.
The World Health Organisation has begun multi-country clinical trials to assess the effectiveness of four of the most promising experimental therapies to treat Covid-19. The drugs undergoing trials are antiviral remdesivir, which shuts down viral replication by inhibiting a key viral enzyme; the anti-malaria drugs chloroquine and hydroxychloroquine that work by decreasing the acidity in endosomes; a combination of the antiretrovirals ritonavir and lopinavir that are used to treat HIV; and ritonavir/lopinavir and interferon-beta, which regulates inflammation and is used to treat multiple sclerosis and chronic hepatitis-C infection.
Other drugs may be added, based on emerging evidence, said the WHO.
“Monoclonal antibodies are an established cancer therapy that is used to treat specific types of cancers, such as cancers of the breast and blood. It’s against Sars-CoV2 is promising but needs extensive and robust human trials to establish whether it stops Covid-19 infection and helps patients recover,” said Dr SVS Deo, head of surgical oncology, All India Institute of Medical Sciences.
