The Drugs Controller General of India (DCGI) has approved the use of the monoclonal antibody injection Itolizumab for ‘restricted emergency use’ for COVID-19 patients. The drug is manufactured by Indian pharmaceutical company, Biocon, and can now be used in the treatment of COVID-19 patients with moderate to severe acute respiratory distress.
The DCGI approval is conditional. Under restricted emergency use, taking the patient’s oral and written informed consent before prescribing the medicine will be required.
It must be known that Itolizumab is already available in the market for the treatment of psoriasis, a skin-related disease. Bengaluru-based Biocon had developed the drug in 2004, after which it was licensed by Center for Molecular Immunology, a cancer research institute in Cuba as an early-stage asset. The DCGI approved it in 2013 for treating psoriasis under the brand-name ‘Alzumab’.
Ever since the permission for its use for COVID-19, Itolizumab has been at the centre of discourse. However, experts believe that the study which this approval is based on has multiple shortcomings.
Itolizumab Gets Approved for Use in Just 120 Days
In a press release from 13 July, Biocon shared that a randomized clinical trial on 30 coronavirus patients at four hospitals in Mumbai and Delhi. 20 patients were randomized to receive Itolizumab with the supportive care, while 10 patients received best supportive care alone in the control arm.
The company said that all 20 patients who were administered the drug did not need ventilator support, unlike those in the control arm. While these 20 recovered fully, were weaned off oxygen by Day 30, and were discharged from the hospital, three out of ten patients in the other group died.
Kiran Mazumdar-Shaw, Executive Chairperson, Biocon, said, “Itolizumab is a ‘Made in India,’ ‘Innovated in India,’ first-in-class anti-CD6 monoclonal antibody, which has a seven-year proven track record of safety as doctors in India have been prescribing this biologic therapy to treat acute psoriasis.”
“The study results show that Itolizumab’s unique mechanism of action can bring down mortality in moderate to severe ARDS patients due to COVID-19.”Kiran Mazumdar-Shaw
In a channel interview, she said that a full course of Itolizumab would cost Rs 32,000, adding that this is much lower when compared to the cost of an ICU treatment.
According to a media report, Kiran Mazumdar Shaw also said that the company moved from applying for commencement of trials on coronavirus patients to getting the final approval for commercialisation in a matter of about 120 days.
Trial on 30 Patients Not Enough, Say Experts
Speaking to FIT, Dr Arvinder Soin, Chairman, Medanta Liver Institute, said, “The trial included 30 participants. Three out of the 10 who were not given the drug died. We don’t know how critical these patients were in the beginning. In such a small sample size, we don’t get answers to a lot of pertinent questions. Therefore, it won’t be right to call it a ‘wonder drug’ based on a study of just 30 patients.”
Dr SP Kalantri, Professor of medicine and medical superintendent, MGIMS Sevagram, said, “The approval has been given on the basis of the phase 2 trial. They have been excused from conducting the third phase of the trial, which typically involves thousands of participants. The company has been told to skip directly to phase 4, which involves monitoring patients after they have been given the medicine and informing the government about any observed side-effects.”
Medicines that are given approval based on the urgency and seriousness of the times without conducting all trials are called ‘compassionate drugs’. However, this doesn’t apply to Itolizumab because trials can be conducted for its effectiveness in India. But involving only 30 patients seems more like a formality than a legitimate search for a safe and effective medicine.
Dr Soin explains that phase-III trials are crucial to truly assess a drug for a disease and to show that it offers benefit over the current treatment options being used.
According to Dr Kalantri, if the medicine is not used carefully and appropriately, it could lead to serious, even fatal side-effects in COVID-19 patients, especially those suffering from TB or malnutrition.
Moreover, the study is yet to be peer-reviewed, which is another drawback.
“When a drug is introduced anywhere in the world, research conducted on it is published in a scientific journal, which is then reviewed by the scientific community. None of that is happening here. Instead, this medicine is just directly being publicised through the media. This is against the core principles of science. Research on other drugs like remdesivir and hydychloroquine was first published, and then they were approved for usage.Dr SP Kalantri
Why Is This Drug Being Used for COVID-19 Treatment?
Why is a psoriasis medicine being considered for COVID-19 patients?
This is because both the conditions are related to the immune system. When the immune response is overactive and attacks the healthy cells in a body, these cells tend to multiply faster than normal. This can cause psoriasis, where bumpy red patches covered with white scales develop on parts of the skin.
COVID-19 can also cause an overactive immune response. When the immune system, which should ideally be targeting antigens that enter the body, turns against the healthy tissues and starts attacking them as well, the results can be lethal. This overreaction of the immune system is known as a ‘cytokine storm’, causing blockages and organ failures.
Itolizumab helps contain this overreaction, which is why it could be considered in moderate to severe coronavirus patients on oxygen support. It is not to be given in the initial phases of the disease because the body is trying to fight the virus with its own natural mechanisms at this time.
Dexamethasone Also Helps Control Cytokine Storm
Dr Soin explained that currently in India, three drugs can be used to contain the body’s overactive response.
These are not for standard use and cannot be used on all patients.
The medicines are Dexamethasone, Tocilizumab and now Itolizumab. While their cellular reaction of action and molecular level mechanism is different, they ultimately help control cytokine storm.
Dexamethasone is cheap, costs less than 30 paise, a strip of 10 comes at Rs 3, and some 20 companies make the drug in India. Dr Kalantri adds that the steroid is being used since decades and doctors and nurses are well aware of when and how to administer it. In that sense, how justified would it be to use a new and expensive drug like Itolizumab, of which we have little knowledge with respect to its side effects, in a developing country?
An Oxford University team studied around 2000 hospitalised patients who were given dexamethasone, and this group was compared to 4,000 who did not receive the medicine. The risk of death was brought down from 40% to 28% for patients on ventilators, and from 25% to 20% for those needing oxygen.
Dr SP Kalantri also believes that even in the control group of 10 patients in the Itolizumab trial, dexamethasone should have been given. By not administering them this steroid, the group was weakened, making it an unfair comparison with the other group. It’s possible that if these 10 people were given dexamethosone, their lives could have been saved. “The groups were not balanced,” he said.
(At The Quint, we are answerable only to our audience. Play an active role in shaping our journalism by becoming a member. Because the truth is worth it.)