JOIN USCovid-19: Will Biocon's Itolizumab pass the test?
Amidst slow-proceeding clinical trials, Biocon’s Itolizumab has sparked a controversy between medical professionals. Itolizumab was approved by the Drug Controller General of India (DCGI) on July 11 to treat moderate to severe cases of Covid-19 cases. It would treat cytokine release syndrome (inflammatory syndrome causing fever or multiple organ dysfunction) in 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 marketed by Cipla and Roche, which is also used to treat Covid-19 patients, a Moneycontrol article reported.
“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 wrote in The Wire.
What is the controversy?
After DCGI approved the drug, Itolizumab drew criticism for not adhering to regulations of a clinical trial. They pointed out that the sample size of the clinical trial is small, hence, difficult to draw verifiable results. The clinical trial enrolled a total of 30 hospitalised Covid-19 of which 20 were administered the drug and the rest were part of the control group. The goal was to check the mortality at 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 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.
Commenting on not implementing Phase-3, Dr Rao said that the lack of clearly stated randomisation plan raises doubts whether 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.
Biocon has also drawn criticism from experts for announcing the clinical trial to the media before publishing it in a peer-reviewed journal. Doing so would have allowed independent experts to assess the claims made by Biocon.
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.
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. In an interview to India Today and Managing Director of Biocon, Kiran Mazumdar-Shaw explained that a 100-patient trial to test Itolizumab would have taken three months.
She also said that the trial data will be published to strengthen the evidence of the effectiveness of Itolizumab.
DCGI’s role
Criticising the DCGI for waiving Phase-3 of the trial, some members of the medical community have demanded that the minutes of the Subject Expert Committee (SEC) meeting be made public. To avoid conflict of interest, some have asked to disclose the names and professional details of SCE members.
Biocon has refused to do so saying that the kind of scientific discussions the committee had is of a “very high order.”