Demand for antibody cocktails soars and clogs hospitals, despite Omicron’s reduction in effectiveness

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

“I have patients who are waiting outside of the outpatient department for the monoclonal antibody cocktail,” Ravishankar said. “Demand has increased for a week.

At Breach Candy Hospital in South Mumbai, around 20 to 30 patients receive the monoclonal antibody cocktail every day in a dedicated day care unit.

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

New evidence shows that the monoclonal antibody cocktails available in India may be ineffective against the Omicron variant of the coronavirus. The country’s top health experts have warned against their use because Omicron is prevalent, at least in Indian cities.

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

The demand has even pushed up the hospitalization rate in Mumbai, according to city officials. Data up to January 5 showed that 36.6% of the city’s total Covid-related hospitalizations are in the private sector. Doctors at private hospitals have said many of these patients are those admitted for an infusion of the monoclonal antibody cocktail.

Even though it only takes two to four hours to administer the cocktail drug, Dr Jalil Parkar, pulmonologist at Lilavati Hospital, said that “some patients need insurance coverage because this hospitalization is obligatory, we therefore admit them for 24 hours “.

“It’s like chocolate for kids, everyone wants it,” said Dr N Santhanam, general manager of Breach Candy Hospital in Mumbai.

How it works

Monoclonal antibodies are proteins made in the laboratory that mimic an antibody to elicit a faster immune response in the body against the coronavirus and prevent serious illness. They target advanced proteins on the surface of the virus to prevent 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 received a combination antibody in October 2020 when he was diagnosed with Covid-19. In May 2021, the Central Pharmaceutical Standards Supervisory Organization of India granted emergency use authorization to Regeneron’s Casirivimab and Imdevimab antibody cocktail, or REGEN-COV.

Global data released by Regeneron partner Roche on 4,567 patients in March 2021 showed that the cocktail of antibodies to Casirivimab and Imdevimab reduced hospitalizations or deaths by 70% and shortened the duration of symptoms of four days.

That same month, US-based Eli Lilly and Company also obtained emergency use authorization for its cocktail of antibodies bamlanivimab and etesevimab.

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

Why this may not work against Omicron

A pre-print Dec. 15 at MedRxiv studied serum from vaccinated and previously infected individuals and used monoclonal antibody therapy in the lab 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 neutralization titers,” indicating the reduced effectiveness of monoclonal antibody therapy against the new variant.

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

So what causes the Omicron variant to make antibody cocktails ineffective? This variant has 32 mutations in its spike proteins compared to the original Sars-CoV-2 virus. Since the spike proteins help the virus enter the host cell, mutations in the spike proteins make it more efficient at evading an antibody response.

On December 16, Regeneron Pharmaceuticals released a statement claiming that its antibody therapy had “reduced potency compared to Omicron but is active against the predominant variant Delta.” Eli Lilly in a statement last month also said he observed “reduced neutralization activity” against the Omicron variant.

On December 16, Regeneron Pharmaceuticals released a statement claiming that its antibody therapy had “reduced potency compared to Omicron but was active against the predominant variant Delta.” | Regen-Cov

Early research indicates two antibodies that 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 in clinical trials. None of them are available in India.

Pros and cons

India’s top health experts have spoken out against the use of monoclonal antibody cocktail therapy in light of Omicron’s spread in cities.

Virologist Dr Gagandeep Kang said that 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 Immunization Technical Advisory Group in India, said: “Monoclonal antibody therapy has no role to play in the treatment of Covid-19 at this time. There is also a financial aspect. Despite the enormous cost, the treatment does not help the patients. “

But antibody cocktail therapy appears to be following the trend seen by remdesivir, tocilizumab, and plasma therapy at different points in the pandemic. Patient-oriented demand keeps its use rampant.

Dr Santhanam, CEO of Breach Candy Hospital, said: “We are informing patients that there is an evolution in research around monoclonal antibodies and that they are only recommended for 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 Mumbai Hospital, consulting physician Dr Gautam Bhansali said the cocktail is only given if patients and their families insist on its use.

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

Among doctors, there remains a debate on the effectiveness of the cocktail. Dr Jalil Parkar, pulmonologist at Lilavati Hospital, said he has stopped using remdesivir, tocilizumab and other antiviral drugs on Covid-19 patients, but continues to use the cocktail of monoclonal antibodies. “The monoclonal helps patients recover faster,” he said, adding that he had found the cocktail to be effective even among the current group of patients, who may be infected with the Omicron variant.

At the government-run Seven Hills Hospital, Dean Dr Balkrishna Adsul said he administered the cocktail of monoclonal antibodies to 25 patients infected with the Omicron variant. “Within 48 to 72 hours, their symptoms started to improve. Clinically, we are seeing improvement in patients, ”he said. Seven Hills Hospital administers the cocktail of antibodies to people over the age of 45 with co-morbidities and at risk for serious illness.

Some experts point out that since most cases of Omicron are mild, patients can recover even without a monoclonal antibody. Adsul said they did not study a control group to compare results if the antibody cocktail was not given to patients.

Dr Ashwin Rajenesh, associate professor in the emergency medicine department at the NS Memorial Institute of Medical Sciences in Kerala, said it was important to identify which patients could benefit from the drug. “If used early in high risk patients, disease progression can be stopped,” he said. “In Kerala, genome studies show that we still have Delta floating around. Therefore, we still use it.

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

This reporting was supported by a grant from the Thakur Family Foundation. Thakur Family Foundation has no editorial control over the content of this article.

Sara H. Byrd