Recently, the Drugs Controller General of India (DCGI) approved “restricted emergency use” of Itolizumab. It is the first anti-CD6 novel biologic therapy to be approved for emergency use, anywhere in the world, for treating patients with moderate to severe COVID-19 complications. However, the Ministry of Health and Family Welfare (MoFHW) has decided against including Itolizumab in the clinical management protocols.

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Itolizumab will be manufactured and formulated as an intravenous injection by Biocon in Bangalore. Biocon has repurposed Itolizumab, an anti-CD6 IgG1 monoclonal antibody launched in India in 2013 for treating chronic plaque psoriasis, for the treatment of cytokine release syndrome (CRS) in moderate to severe ARDS (acute respiratory distress syndrome) patients due to COVID-19.

According to a study, diseases such as COVID-19 and influenza can be fatal owing to an overreaction of the body’s immune system called a cytokine storm. Cytokines are small proteins released by many different cells in the body, including those of the immune system where they coordinate the body’s response against infection and trigger inflammation, the study added.

Giving an example, the study added that when SARS-CoV-2 enters the lungs, it triggers an immune response, attracting immune cells to the region to attack the virus, resulting in localised inflammation. But in some patients, excessive or uncontrolled levels of cytokines are released. They then activate more immune cells, resulting in hyper inflammation, which can seriously harm or even kill the patient.

The drug can regulate or block the immune response in order to prevent a cytokine storm. The DCGI approved an injection of Itolizumab with dosage 25 mg/5 mL solution in India, for the treatment of cytokine release syndrome (CRS) in moderate to severe ARDS patients due to COVID-19. A single dose comprises four 25 mg/5 mL injection vials for a person who weighs 60 kg.

Talking to the media, Dr. Sandeep Athalye, Chief Medical Officer, Biocon Biologics, stated that Itolizumab demonstrated a statistically significant advantage over the control arm in one-month mortality rate. “Key efficacy parameters such as PaO2 and SpO2 (oxygen saturation) improvement without increasing FiO2 (oxygen flow) also showed a statistically significant advantage for Itolizumab arm over the control arm. All the patients on Itolizumab arm were weaned off oxygen by day 30, and none needed ventilator support, unlike in the control arm.”

Testing Method

The emergency use approval of Itolizumab, from the DCGI, is based on the results from the successful conclusion of randomised controlled clinical trials at multiple hospitals in Mumbai and New Delhi. The study focussed on the safety and efficacy of Itolizumab in preventing CRS in moderate to severe ARDS patients due to COVID-19. The primary endpoints for the reduction in mortality rate were met and other key secondary endpoints for efficacy and biomarkers were also achieved.

Ten severely ill patients suffering from COVID-19 participated in the trial conducted by King Edward Memorial (KEM) Hospital at Parel, Mumbai, for Itolizumab. A 35-year old patient, who was initially tested and was on the ventilator, and was taken off from the ventilator in three days of the use of the drug. The patient’s pneumonitis in the left lower zone improved.

Itolizumab’s mechanism of action of immunomodulation involves binding to the CD6 receptor and blocking the activation of T lymphocytes, which in turn suppresses the pro-inflammatory cytokines. This reduces the cytokine storm and deadly inflammatory response, said a press release by Biocon.

ICMR not convinced

However, the Indian Council of Medical Research (ICMR), the apex Indian body for medical research, is not in favour of the drug and Biocon's claim yet. Talking to the media, Balram Bhargava, director general of ICMR, stated that Biocon has not yet demonstrated mortality reduction by any trial and therefore. Trials are happening in different parts of the world, to look at whether there is mortality reduction with the drug.

Currently, the drug is on hold as the COVID-19 national task force also believes that there is a lack of evidence to prove the drug’s efficiency. The national task force also asked for more data from Biocon to prove the claim.

Dr. Hemant Thacker from Bhatia and Breach Candy Hospitals, Mumbai stated that the drug is useful for the patients who are on a ventilator to get them off earlier. It shows no side effects if used once in six or seven hours and can be used to lower the mortality rate but as far as COVID-19 is concerned, it is not a solution.