Confusion and critique preceded data on 11 July when the Indian drug regulator approved Biocon’s biotech drug Itolizumab to treat moderate-to-severe cases of Covid-19.
Itolizumab a monoclonal antibody already in use for seven years to treat psoriasis has been repurposed for Covid-19. Like every other drug so far. As soon as the news broke some professionals questioned the size of the sample on which the drug was tested.
Result: A drug that should have made headlines got mired in doubts. A drug that is approved in India is getting into a multi-site trial in Mexico Brazil and the United States next month.
The Indian regulator hasn’t been releasing data for the drugs it has approved. But on 13 July Biocon shared comprehensive data in a press conference
Looking at the data and listening to at least eight doctors on the Zoom press conference it’s clear that Itolizumab is a life-saving drug in cases where doctors notice or anticipate an aggressive immune response called the cytokine-release storm. In the 3-5% cases that get hospitalised for Covid-19 cytokine storm is the leading cause of death.
First the science.
The drug acts upstream in the body; it gets the cells to stop producing cytokines and acts against at least three cytokines. (Yes the storm is a mixture of many cytokines.) Another monoclonal antibody Tocilizumab from the Swiss major Roche and which is also being used for Covid works downstream and manages the disease once the storm has kicked in. Proactive vs reactive.
Itolizumab was originally discovered in Cuba; Biocon licensed it in 2003 and developed it in India for psoriasis. It has sold its US rights to its partner Equillium which is testing the same drug for three indications—asthma graft vs host disease and lupus nephritis. Equillium is now fast-tracking the fourth indication—Covid-19.
Now the criticism.
The Hindu headline: “Experts question basis of Covid-19 drug”
The drug was tested on 20 patients in the experimental group; 10 patients in the control group did not get this drug—they received standard of care. The trial was designed using a method called Simon’s Two-Stage design often used for testing novel drugs for orphan diseases where the number of patients is inherently small.
Within the trial period three patients died in the control group but none in the experimental group.
Biocon’s chief medical officer Dr Sandeep Athalye told me that if the primary goal of a drop in mortality rates wasn’t achieved they’d have extended the trial period. “Suppose there was one death in each group we’d have extended the trial or added more people.”
For chairman Kiran Mazumdar-Shaw the reason to do a quick pivotal trial was to “not deny a life-saving treatment” to people. “If we did a 100-patient trial it’d have taken us three months” she told me. “I had state governments asking for this drug because they saw their doctors use it off-label and save lives.”
Not only was she privy to encouraging clinical results from nearly 150 patients outside the trial predominantly in Maharashtra she also had Cuban patient data. In a 76-patient trial of severely ill Covid-19 patients in Cuba 79.2% were discharged from ICU within 14 days.
A full course of Itolizumab—four vials of the injectable drug—will cost Rs 32000. Dr Athalye says they’ll continue to gather real world data and build on the trial data. A scientific publication is in the works too. Needed urgently because:
Biocon possibly has another window of opportunity—to look at instances where cytokine storm is a critical issue such as septic shocks or post-transplantation complications.
Science is a pursuit of truth not a treasure hunt they say. For Biocon Itolizumab may prove to be both.
As for several other monoclonal antibodies under repurposing studies Itolizumab shows Covid-19 could be another disease to attack