On January 4, the chief operating officer of Mumbai’s Lilavati Hospital, Dr V Ravishankar, was flooded with phone calls from family members of Covid-19 patients calling to ask if they could come for a dose of the monoclonal antibody cocktail therapy.

“I have patients waiting outside the out-patient department for the monoclonal antibody cocktail,” Ravishankar said. “Demand has increased since a week.”

At south Mumbai’s Breach Candy Hospital, every day about 20-30 patients receive the monoclonal antibody cocktail at a day-care unit specially assigned for this purpose.

In Delhi, at Max Hospital in Saket, doctors said patients are lining up for the therapy, which aims to shore up the body’s defences against the coronavirus. But Dr Vivek Nangia, head of the pulmonology department, said they are “consciously reducing its use except for rare cases”.

Emerging evidence shows that the available monoclonal antibody cocktail drugs in India may be ineffective against the Omicron variant of the coronavirus. The country’s top health experts have cautioned against their use since Omicron is widespread, at least in Indian cities.

But as Covid-19 cases explode, so has the demand for the cocktail therapy among those who can afford it – a single dose costs Rs 65,000.

The demand has even pushed up the hospitalisation rate in Mumbai, civic officials say. Data until January 5 showed that 36.6% of total Covid-related hospitalisations in the city are in the private sector. Doctors at private hospitals said many of these patients are those admitted for an infusion of the monoclonal antibody cocktail.

Even though it takes just two to four hours to administer the cocktail drug, Dr Jalil Parkar, pulmonologist at Lilavati Hospital, said that “some patients require insurance cover, for that hospitalisation is mandatory, so we admit them for 24 hours.”

“It is like a chocolate for children, everybody wants it,” said Dr N Santhanam, chief executive officer at Mumbai’s Breach Candy Hospital.

How it works

Monoclonal antibodies are laboratory-made proteins that mimic an antibody to evoke a faster immune response in the body against the coronavirus and prevent severe disease. They target the spike proteins on the surface of the virus to stop it from entering human cells and multiplying.

The antibody cocktail is administered intravenously or subcutaneously through the skin – a procedure that takes two to four hours.

The therapy gained popularity after former United States President Donald Trump was administered a combination of antibodies in October 2020 when he was diagnosed with Covid-19. In May 2021, India’s Central Drugs Standards Control Organisation granted emergency use authorisation to Regeneron’s Casirivimab and Imdevimab antibody cocktail, or REGEN-COV.

Global data published by Regeneron’s partner Roche of 4,567 patients in March 2021 showed that the antibody cocktail of Casirivimab and Imdevimab reduced hospitalisation or death by 70% and shortened the duration of symptoms by four days.

The same month, Eli Lilly and Company, based in the United States, was also granted emergency use authorisation for its antibody cocktail bamlanivimab and etesevimab.

In India, the use of the antibody cocktail has increased in the last seven months, especially in cases of the Delta variant against which it has proven to be effective. But evidence suggests it is not effective against Omicron.

Why it may not work against Omicron

A pre-print on December 15 in MedRxiv studied serum from vaccinated and previously infected individuals and used the monoclonal antibody therapy in a laboratory setting to see if it could stop the entry of the Omicron variant into human cells and prevent multiplication. The study found a “17 to 22-fold reduction in neutralisation titres”, indicating the reduced efficacy of monoclonal antibody therapy against the new variant.

Another pre-print in BioRxiv studied the effectiveness of nine antibody cocktails against Omicron and found that the variant was totally or partially resistant to the therapies.

So, what makes the Omicron variant render antibody cocktails ineffective? This variant has 32 mutations in its spike proteins compared to the original Sars-CoV-2 virus. Since spike proteins help the virus gain entry into the host cell, mutations in spike proteins make it better at evading an antibody response.

On December 16, Regeneron Pharmaceuticals issued a statement saying its antibody therapy had “diminished potency versus Omicron but are active against predominant Delta variant”. Eli Lilly in a statement last month also said it observed “reduced neutralisation activity” against the Omicron variant.

On December 16, Regeneron Pharmaceuticals issued a statement saying its antibody therapy had “diminished potency versus Omicron but are active against predominant Delta variant”.| Regen-Cov

Early research points to two antibodies which may be effective against the Omicron variant: Sotrovimab, developed by San Francisco-based Vir Biotechnology and London-based GSK, and DXP-604, developed by Beijing-based BeiGene and Singlomics. DXP-604 is currently undergoing clinical trials. Neither of them are available in India.

For and against

India’s top health experts have been vocal about avoiding the use of the monoclonal antibody cocktail therapy in light of the spread of Omicron in the cities.

Virologist Dr Gagandeep Kang said there is enough evidence to suggest that the monoclonal antibody cocktail drugs available in India are not effective against the Omicron variant. Dr NK Arora, member of the National Technical Advisory Group on Immunisation in India, said, “Monoclonal antibody therapy has no role to play in Covid-19 treatment right now. There is a financial component too. Despite the huge cost, the treatment does not help patients in any way.”

But antibody cocktail therapy seems to be following the trend that remdesivir, tocilizumab and plasma therapy witnessed at different points during the pandemic. A patient-driven demand is keeping its use rampant.

Dr Santhanam, chief executive officer at Breach Candy Hospital, said, “We inform patients that there is evolving research around monoclonal antibody and it is recommended for only a selected group of patients. But sometimes some patients insist on being administered,” he said, adding that “cost is not a concern for the affluent section.”

At Bombay Hospital, consultant physician Dr Gautam Bhansali said the cocktail is administered only if patients and their families insist on its use.

In Delhi’s Max Hospital, however, Dr Nangia said he sparingly uses the cocktail. “It was effective against Delta, but with Omicron we don’t know yet. Assuming most cases now are of Omicron we are making a conscious effort to reduce its use,” he said.

Amongst doctors, there remains a debate over the effectiveness of the cocktail. Dr Jalil Parkar, pulmonologist at Lilavati Hospital, said that he had stopped using remdesivir, tocilizumab and other anti-viral drugs on Covid-19 patients, but continues to use the monoclonal antibody cocktail. “Monoclonal is helping patients recover faster,” he said, adding that he found the cocktail was effective even among the current pool of patients, who could be infected with the Omicron variant.

At the government-run Seven Hills Hospital, dean Dr Balkrishna Adsul said he administered the monoclonal antibody cocktail to 25 patients infected with the Omicron variant. “Within 48-72 hours their symptoms started subsiding. Clinically, we are seeing improvement in patients,” he said. Seven Hills Hospital administers the antibody cocktail to those aged over 45 years with comorbidities and at risk of severe disease.

Some experts point out that since most Omicron cases are mild, patients may recover even without the monoclonal antibody. Adsul said they have not studied a control group to compare the outcome if the antibody cocktail is not given to patients.

Dr Ashwin Rajenesh, associate professor in the Department of Emergency Medicine at NS Memorial Institute of Medical Sciences in Kerala, said it was important to identify which patients stood to benefit from the drug. “If used early in patients at high risk, the disease progression can be halted,” he said. “In Kerala, genome studies show we still have Delta floating around. Hence we are still using it.”

But Rajenesh cautions that the monoclonal antibody cocktail is sensitive and requires preservatives to remain stable. “It can cause chemical allergic reactions too. We cannot allow indiscriminate use,” he said.

This reporting was supported by a grant from the Thakur Family Foundation. Thakur Family Foundation has not exercised any editorial control over the contents of this article.