NEW DELHI – Bangalore-based Biocon Ltd. has received the Indian drug regulator's approval for restricted emergency use of its psoriasis biologic, itolizumab, to treat patients with severe cases of COVID-19 in need of ventilator support.

Itolizumab, an immunomodulatory drug developed jointly by Biocon and the Centre of Molecular Immunology, Havana, has been used in India since 2013 to treat acute psoriasis, and has a seven-year track record of safety, Biocon’s executive chairperson, Kiran Mazumdar Shaw, said.

Shaw described itolizumab as the "first-in-its-class novel biologic therapy for treating moderate to severe acute respiratory distress syndrome [ARDS] caused by COVID-19.”

The drug is for emergency restricted use only in moderate to severe cases to prevent the need for ventilators to combat the spread of the disease. Itolizumab will be manufactured and formulated as an intravenous injection at Biocon’s biomanufacturing facility in Bangalore. The company plans to first meet India’s requirements for the drug, and then plans to “take this therapy to other parts of the world impacted by the pandemic.”

“Medical specialists have observed that in patients with severe COVID-19 infections, the virus triggers an overreaction of the immune system,” Shaw said.

The hyperactivated immune system produces a large number of cytokines, small proteins or peptides which act as signaling molecules and impact communication between cells. The excessive production of cytokines by immune cells, a cytokine storm, can severely damage the lungs and other organs, and, in the worst-case scenario, result in multi-organ failure and even death.

The repurposed drug is a genetically engineered monoclonal antibody that acts against CD6 receptors on T cells. By binding to CD6 cells, it prevents their proliferation and reduces inflammation.

The Drug Controller General of India (DGCI) approved the restricted emergency use of itolizumab, on the basis of the results from a randomized, controlled clinical trial at multiple hospitals in Mumbai and New Delhi, two of India’s worst-hit cities.

“The phase I and phase II trials were based on a small sample size of 20 patients who received the standard care plus itolizumab, and 10 control patients who only received standard care,” Sandeep Athalye, chief medical officer, Biocon Biologics, a subsidiary of Biocon, told the media on July 13. All patients in the treatment group recovered while there were three deaths in the control group.

The results are similar to findings from a similar independent clinical trial in Cuba, where 76 COVID-19 patients were treated with itolizumab. “At the end of the trial, 79% of severely ill patients were discharged from the ICU after 14 days of treatment, while moderately ill patients showed a reduction in the rate of disease progression,” Shaw said.

“The primary endpoints were reduction in death rates and other key secondary endpoints were efficacy and identification of biomarkers,” Athalye added.

An itolizumab injection costs $103 (Rs7800) per vial of 25-mg/5 ml solution. Usually four injections are needed, though a few patients may require six.

Some doctors in the Delhi and Mumbai hospitals involved with the itolizumab trials reported patient recovery with the drug. One such hospital is the public-funded Lok Nayak Hospital in Delhi. Suresh Kumar, medical director of Lok Nayak Hospital, said his team used the drug to treat eight patients. “These patients did extremely well even with a single dose,” he said adding that patients who would have otherwise been put on ventilator support with little chance of survival recovered completely.

Similarly, BYL Nair Hospital in Mumbai has tried itolizumab in moderate to severe COVID-19 patients. Mohan Joshi, dean of BYL Nair Hospital, said that doctors found “significant improvement in clinical, radiological and inflammatory markers after administering itolizumab.”

In some other cases, for example at a hospital in Solapur town near Mumbai in Maharashtra state, which was not a trial site, doctors independently gave itolizumab as a cheaper alternative to the anti-inflammatory injectable drug tocilizumab, whose single dose costs $598 (Rs45,000). Patients require a minimum of two doses of tocilizumab, which many patients in India cannot afford, Vishal Gore, a consultant physician with the Markandaya Hospital and CNS Hospital in Solapur, said.

“As Biocon’s itolizumab is targeted at patients with moderate to severe ARDS and oxygen saturation of less than 94%, it is positioned for more severe cases and the addressable market could be limited to about 10% to 20% of all COVID-19 cases,” Pushpa Vijayaraghavan, who leads the Healthcare and Life Sciences Advisory Practice at Sathguru Management Consultants, told BioWorld.

Given the price competitiveness, if the drug gains substantial share of that market for moderate to severe cases, peak market potential could be around $39.88 million (Rs3000 million), she said.

“However, the negligible level of validation, i.e. 30-patient pivotal trial, could be an impediment to realizing this market potential,” Vijayaraghavn observed. “Especially in comparison to data benchmark set by the RECOVERY trial where dexamethasone was established as beneficial in patients requiring respiratory support based on data from 6,425 patients.”

A randomized evaluation of COVID-19 therapy, the RECOVERY trial at Oxford University, is currently testing four treatment options – low-dose dexamethasone, commonly used antibiotic azithromycin, tocilizumab and convalescent plasma collected from donors who have recovered from COVID-19 and have antibodies against the virus.

In India, doctors currently are using the antimalarial hydroxychloroquine, which binds with the receptor through which the virus enters the human cells, for early stage infections; the antiviral drug remdesivir (Gilead Sciences Inc.), which interrupts viral multiplication inside the cells for early stage infections; the anti-inflammatory tocilizumab, which is under clinical trials to treat moderate to severe patients; the antiviral favipiravir for mild to moderate cases; and convalescent plasma therapy.

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