- India's drug regulator has granted an emergency approval to the antibody drug itolizumab to treat the potentially deadly immune response, cytokine release syndrome, that appears to affect some patients hospitalized with acute respiratory distress related to COVID-19.
- The Drugs Controller General of India cleared the treatment for use after itolizumab, alongside standard of care, reduced the rate of death versus standard treatment alone in a 30-patient, controlled trial in India, according to its developer, Biocon.
- Biocon shared few details, and the results are from a very small trial. But itolizumab appears to be just the second drug thus far, following the steroid dexamethasone, to have shown a survival benefit in a well-controlled trial of COVID-19 patients. La Jolla, CA-based Equillium holds some rights to itolizumab and plans to start a global study, news that sent the small biotech's shares up more than 150%.
The battle against the new coronavirus is being waged on multiple fronts, from vaccines to prevent infection to other drugs meant to treat and manage COVID-19's many complications.
One of those complications is an overactive immune response, seemingly similar to cytokine release syndrome or CRS, which can cause potentially deadly damage to the lungs or other organs.
Researchers and scientists have been testing other anti-inflammatory drugs against that damaging immune response, but thus far have yet to succeed. The Sanofi and Regeneron arthritis drug Kevzara has failed to deliver a clear benefit in clinical trials, while a similar drug from Roche came up short in a small Italian study after flashing promise earlier.
A larger, more rigorous Actemra trial is still underway, as are tests of the cancer therapies Jakafi and Calquence.
The only drug that has conclusively been shown to reduce death in a large trial of hospitalized COVID-19 patients is the steroid dexamethasone.
But that study, called RECOVERY, didn't look at whether patients where suffering from immune responses characteristic of CRS. Indeed, the mass repurposing of drugs to target COVID-19 related CRS has alarmed some experts, fearful of causing more harm than good.
A JAMA editorial published in late June highlighted that what is being defined as "cytokine storm" isn't fully understood, and treating those patients with drugs that indiscriminately suppress the immune system "raises concerns about impaired clearance of SARS-CoV-2 and increased risk for secondary infections."
Yet Indian drugmaker Biocon, the developer of plaque psoriasis drug called itolizumab, has claimed success in a study of 30 patients hospitalized with COVID-19 who have CRS and moderate to severe acute respiratory distress syndrome. Biocon reported that in a controlled trial, all 20 people who got itolizumab and standard treatment recovered. Three of the 10 on standard treatment alone died. Decreases in various key markers of inflammation — as well as measures of oxygen levels — were seen in itolizumab patients as well, according to the company.
Biocon has not provided specifics yet, however, making its claims impossible to fully assess. Still, the results were encouraging enough for the Indian government to clear use of itolizumab in very sick COVID-19 patients. That, along with additional data being generated in Cuba, where the drug was discovered, "could pave the way for discussions with regulators and other government agencies to pursue clinical development and funding in the U.S.," wrote SVB Leerink analyst Thomas Smith.
Results from an open-label, uncontrolled 24-patient study in Cuba currently under a peer review at the journal Immunity & Ageing found that itolizumab appeared to significantly reduce levels of the inflammatory protein IL-6 in the blood. The Cuban government in May also credited the use of itolizumab for an apparent reduction in deaths from COVID-19 among its citizens, though those results didn't come from a randomized, controlled trial.
Unlike Actemra and Kevzara, which inhibit an inflammatory protein called IL-6, Itolizumab blocks CD6, a protein found on the surface of many immune cells, among them effector T cells that drive inflammation in a variety of diseases. The drug was approved in India in 2013 to treat chronic plaque psoriasis under the brand name Alzumab. Equillium has since licensed rights in the U.S., Canada, New Zealand and Australia and has been aiming to develop it for a number of inflammatory conditions like asthma and lupus.
In light of the news from India, Equillium said it plans to ask the Food and Drug Administration to start a global randomized trial of itolizumab. Equillium shares more than doubled, to over $8 apiece, though that's still less than the $14 per share price at which the company went public in 2018.
Equillium had to stall testing of itolizumab — which it calls EQ001 — due to the pandemic. But it said Monday that those trials have now resumed.