There is yet no evidence from trials that itolizumab and tocilizumab, two drugs, one of which has been developed by Bengaluru-based Biocon Biologics, reduce death in severely ill coronavirus ( COVID-19 )patients, Director-General of the ICMR Balram Bhargava said at a Health Ministry press briefing on Tuesday.
Both drugs are lab-cloned antibodies, and work at thwarting or reducing a rush of chemicals called pro-inflammatory cytokines that are released by the immune system to counter the coronavirus attack on lung cells.
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Cytokines prime the immune system to send special cells to neutralise virus particles. However a ‘cytokine storm’ that’s manifested usually as an Acute Respiratory Distress Syndrome (ARDS) ends up causing inflammation and aggravating lung damage and harm to other organs and is said to be responsible for killing a large fraction of the 3%-5% of COVID-19 patients that die.
Tocilizumab has a history of use in immune-system-disorder diseases such as rheumatoid arthritis, and itolizumab in acute psoriasis.
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The ICMR last month approved the use of tocilizumab on patients who need to be externally oxygenated and those who need ventilators but are not benefiting from steroids. On Monday, Biocon said at a press conference that results from a phase-2 study meant to check a drug’s efficacy showed that the novel biologic, Itolizumab, “significantly reduced mortality” in moderate to severe ARDS (acute respiratory distress syndrome) patients hospitalised with COVID-19, in India.
On Tuesday, Dr. Bhargava said: “There are two drugs which have been thought to be preventing the cytokine storm. One is Tocilizumab and the other is Itolizumab, which are being thought that they can prevent the cytokine storm. Having said that, they have not yet demonstrated mortality reduction by any trial and therefore, trials are wanting, and are happening in different parts of the world, to look at whether there is mortality reduction with these two drugs.”
In response to a question from The Hindu on whether the jury on itolizumab’s efficacy was still out, Kiran Mazumdar-Shaw of Biocon replied via a tweet that “...Pivotal data did show mortality reduction but there was a need for larger Phase 4 trials to support this.”
The drug regulator allowed the medicine — that cost ₹8,000 a vial — to be allowed for Restricted Use Emergency Authorisation, meaning it could be administered to those manifesting severe-moderate to severe ARDS under physician guidance for a limited period.
Itolizumab is an approved drug for acute psoriasis since 2013 and has passed safety and efficacy trials for that disease in over 500 patients. However, independent experts have pointed out, as The Hindu has previously reported, that the efficacy of the drug for COVID-caused ARDS hasn’t been conclusively demonstrated because the phase-2 trial, or the “pivotal data” relied on clinical trial data from only 30 patients.
Importantly the drug regulator — in consonance with Dr Bhargava’s remarks — has cited the drug’s efficacy at moderating the immune response rather than the mortality data — to recommend emergency use. The company would also be required to do a phase-4 clinical trial study on the drug.
Company officials have said more studies, including international ones, are on the anvil and several doctors in reputed hospitals, who’ve tried the drug in patients, have reported benefits, given that there were few treatment options to control a cytokine storm. Moreover the drug is priced at ₹32,000 for a treatment course and reduces hospitalisation time.
