Covid-19: Does Biocon's Itolizumab pass the test?

Amidst slow-proceeding clinical trials, Biocon’s Itolizumab has sparked a controversy among medical professionals. Itolizumab (to be marketed as (ALZUMAb) was approved by the Drug Controller General of India (DCGI) on July 11 for emergency use to treat cytokine release syndrome (inflammatory syndrome causing fever or multiple organ dysfunction) in ARDS patients (acute respiratory distress syndrome) caused by Covid-19.

What is Itolizumab?

Itolizumab is a re-purposed drug that was used to treat psoriasis. It was touted as an affordable alternative of Tocilizumba, an IL-6 inhibitor, which is also used to treat Covid-19 patients.

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“The drug hasn’t been approved by the US’s Food and Drug Administration or the European Medicines Agency as Biocon hasn’t applied for such marketing authorisation,” Dr Jammi Nagaraj Rao, an epidemiologist and public health physician based in, UK told The Wire.

What is the controversy?

After DCGI approved the drug, Itolizumab drew criticism for not adhering to regulations of a clinical trial. Indian Council of Medical Research (ICMR) Director General Balram Bhargava said at a press briefing that there wasn't enough evidence from clinical trials that the drugs Itolizumab and Tocilizumab reduced mortality in Covid-19 patients.

Several experts have pointed out that the sample size of the clinical trial is too small, hence, difficult to draw verifiable results.

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The clinical trial enrolled a total of 30 hospitalised Covid-19 patients, of which 20 were administered the drug and the rest were part of the control group. The goal was to check the mortality after one month.

The group of 20 recovered while the three of the 10 in the control group succumbed to Covid-19.

Phase-3 which demonstrates the efficacy of the clinical trial was waived by the DCGI. In this phase, the drug is tested in multiple centres on a larger demography. Instead, Itolizumab has already been allowed into the market and post-market surveillance (Phase-4) is underway. Critics of the drug have said that it is Phase-3 was an important step and should not have been skipped.

"The lack of clearly stated randomisation plan raises doubts whether the splitting the group into two was actually random or not. Skipping this step also makes the trial unable to meet the international standards of reporting trials," Dr Rao outpointed in the Wire report

Biocon has also drawn criticism from experts for announcing the clinical trial to the media before publishing it in a peer-reviewed journal, which would have allowed scrutiny from independent experts.

What is Biocon’s response?

Responding to the critics, Biocon’s Chief Medical Officer Sandeep Athalye, said that the drug is an extension of an already approved product. He defended the usage of the drug saying that if they were able to show the magnitude of effect in a small trail, which is statistically significant, even a small trial would be enough to demonstrate the power of the drug.

On Twitter, responding to queries on the ICMR-DG’s comments, Biocon’s Executive Chairperson Kiran Mazumdar-Shaw said, “Dr Bhargava is right. We have received Emergency Use Authorisation on a small pivotal trial. As mandated, we will do a larger Ph4 clinical trial n we also have 150 pt real world ‘off label’ data which will be published. She also added that larger trials would be conducted.

Several doctors have used the drug off-label (an approved drug is used to treat a disease it is not approved for) in Maharashtra, Gujarat and Delhi on compassionate grounds and all the patients have been cured of Covid-19, Biocon said.