Does Itolizumab, the latest drug in COVID-19 management, save lives? Probably not, according to the Indian Council of Medical Research.
Itolizumab is a monoclonal antibody which was already approved for severe chronic plaque psoriasis, an autoimmune skin disease. Last week, the drug was granted restricted emergency use authorisation by the Drugs Controller General of India (DCGI), based on data submitted by the Bengaluru-based Biocon Limited.
However, Dr Balram Bhargava, director general, ICMR, refuted the claim that the drug worked to save lives, and said more data was needed to establish efficacy in preventing deaths. “We know that in severe COVID-19 patients, there is a problem of a cytokine storm. Cytokines are released, and they are responsible for a storm that ultimately leads to serious conditions. There are two drugs that are thought to be preventing the cytokine storm, Itolizumab and Tocilizumab. Neither of them have yet demonstrated mortality reduction by any trial. Trials are wanting, and are happening in different parts of the world to look at whether there is mortality reduction with these two drugs,” Bhargava said at the health ministry briefing on Tuesday.
Since 2013, the drug is being manufactured and marketed by Bengaluru-based Biocon Limited under the brand name Alzumab, for the treatment of patients with moderate to severe chronic plaque psoriasis. It has now been re-purposed for COVID-19. According to Biocon, a Phase 2 trial was done on 30 patients, and a 30 per cent reduction in death rate was observed, besides preventing patients from going to a ventilator.
According to Dr Shashank Joshi, dean, Indian College of Physicians, and principal investigator of the trial, the drug has also been used in Cuba, has had data as “exciting” as the Indian data, and doctors have used it off label to “save lives”.
According to the drug regulator, based on the data that has been submitted, Biocon has been asked to conduct Phase 4 clinical trials for the drug. This implies that Phase 3 trials have been waived off for Itolizumab.
The firm also has to submit risk management plan to address safety issues in post marketing scenario. As of now, the drug can only be supplied on a doctor's prescription and informed consent has to be obtained from the patient before administering it.
At Rs 8,000 per vial, the drug costs Rs 32,000 for a full course.
Responding to Bhargava's statement on the lack of data on mortality reduction, Biocon executive chairperson Kiran Majumdar Shaw said a larger study was needed. “Dr Bhargava is right. We have received Emergency Use Authorisation on a small pivotal trial. As mandated, we will do a larger, Phase 4 clinical trial and we also have 150 patient real world ‘off label’ data which will be published...Pivotal data does show mortality reduction, but yes, larger Phase 4 needs to be done to support this. We will start this asap,” she said in a series of tweets.
Several experts have raised concerns over the small size of this trial, the fact that the study results have not been peer-reviewed and published in a journal yet, and the drug regulator's decision to waive off Phase 3 trials.