Monoclonal antibodies: a treatment against covid that you may not know

Dr. Huerta explains how bamlanivimab 2:28 works

(CNN) -

There are very few drugs that prevent people who get coronavirus from developing serious illness.

Monoclonal antibodies may be among them.

Early study results show that they can reduce the rate of hospitalizations by up to 70% if taken on time, which can save lives, especially among people who are at high risk of becoming seriously ill.

But it seems that this information is not reaching the people who need the drug most or their healthcare providers.

Eli Lilly's monoclonal antibody treatment, called bamlanivimab, received an emergency use authorization from the US Food and Drug Administration (FDA) in early November.

Less than two weeks later, the agency granted this authorization to Regeneron's monoclonal antibody cocktail.

This is made up of two monoclonal antibodies, casirivimab and imdevimab, and called REGEN-COV2.

It was the treatment given to President Trump when he became infected in early October.

Former New Jersey Governor Chris Christie and Housing and Urban Development Secretary Ben Carson were also treated with this monoclonal antibody therapy.

In which cases should monoclonal antibodies be administered?

According to the FDA, monoclonal antibodies should be administered as soon as possible after symptoms appear and a person tests positive for infection.

And, due to limited supply, clearances are limited to high-risk patients, such as people 65 years of age or older, those with a BMI (body mass index) of 35 or more, and those with other health conditions such as diabetes, cardiovascular disease or chronic kidney disease.

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'The monoclonal antibodies that we have licensed appear to work best to prevent outpatient hospitalization in the early stages of their disease, usually within 10 days of symptom onset, for high-risk individuals.

(This implies in) those over 65 or over 55 with a comorbidity or (…) a pre-existing disease that puts them at risk, "FDA Commissioner Dr. Stephen Hahn told CNN's Dr. Sanjay Gupta in mid December.

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“During the last month since authorization was granted, these antibodies have been distributed throughout the country.

So they should be available locally and that's under state jurisdiction, ”Hahn said.

Therapy available

At a time when hospitals across the country are running out of beds and staffing to care for the critically ill, monoclonal antibodies may have a real role to play.

So why don't more people try to access these potentially life-saving drugs, especially given that both drugs are mostly free under Operation Warp Speed?

«We have to use the therapy.

We need patients who test positive (and) who are at risk of hospitalization to receive these monoclonal antibodies.

In fact, we now have more of what is being used.

We have to get them sooner, to keep people out of hospitals, "Secretary of Health and Human Services (HHS) Alex Azar told CNN's Jake Tapper on Monday.

An HHS spokesperson confirmed that a new report showed that only 5% to 20% of the available supply of monoclonal antibodies is being used.

It's an ironic statistic, considering that a major concern was that there would not be enough supply to meet demand.

This is the first time that HHS has requested information on the use of the drug by the facilities and providers that administer it.

"We will continue to work with stakeholders to learn more about drug utilization decisions," the spokesperson said.

How Monoclonal Antibodies Work

To fight infection, the immune system produces different types of antibodies that target different parts of the invader, explained Gigi Kwik Gronvall, a senior researcher at the Johns Hopkins Center for Health Safety.

"When you have an infection, your immune system kicks in and produces antibodies," Gronvall said.

'The best antibodies stick to the pathogen.

In this case, they will stick to the virus and prevent the virus from infecting your cells.

Therefore, antibodies have a real role in stopping infections, "he explained.

That is why convalescent plasma therapy is sometimes used to treat coronavirus-infected patients.

This involves taking antibody-containing plasma from someone who has recovered from COVID-19 and infusing it into a sick person in the hope of reactivate their immune response.

But some antibodies work better than others, and different people have different levels of antibodies, so convalescent plasma results are not always consistent.

How does convalescent plasma treatment work?

1:38

Monoclonal antibodies to treat COVID-19 are highly focused, laboratory-made versions of convalescent plasma.

The scientists searched for the antibodies that would best block SARS-CoV-2 virus infection.

"They chose a particular type of antibody, what they call a neutralizing antibody ... and they made a purified version to use as a medicine," Gronvall said.

Some believe evidence for the use of monoclonal antibodies is lacking

Eli Lilly's drug uses one particular antibody and Regeneron's drug uses a combination of two others.

Early study results have shown that they appear to reduce the chances of ending up in a hospital or emergency room by 55% to 70%.

Neither drug is fully approved by the FDA.

And not everyone is convinced that the evidence so far is strong enough to support routine use.

The National Institutes of Health's Covid-19 treatment guidelines, for example, say that "there is insufficient data to recommend for or against the use" of any of the products "for the treatment of outpatients with mild to moderate covid-19 ”.

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Similarly, a guideline panel from the Infectious Diseases Society of America "suggests against the routine use of bamlanivimab for outpatients with COVID-19."

However, the panel noted that some people at increased risk of progressing to severe COVID-19 disease "may reasonably select this treatment after careful discussion with their physician."

It is also important to note that monoclonal antibodies do not appear to help, and can actually harm, people who are hospitalized.

Both Lilly and Regeneron ended trials of their drugs in seriously ill patients.

Limited supply?

Azar told reporters at an Operation Warp Speed ​​briefing in mid-December that more than 278,000 full treatments from the two companies have been sent to medical facilities and that the administration is working to send more.

The government initially bought 300,000 doses of bamlanivimab and in early December it bought an additional 650,000 doses, according to a statement by Eli Lilly, which also says that it 'continues to manufacture bamlanivimab for use around the world, and the supply is expected to increase substantially in 2021 ».

A statement from Regeneron states that it "expects to have treatment doses ready for approximately 80,000 patients before the end of November, for approximately 200,000 patients by the first week of January, and for approximately 300,000 patients before the end of January 2021."

2021 target

While that may seem like a large number of doses in total, they come at a time when new coronavirus cases per day in the United States alone average more than 215,000.

However, it is important to note that not all people who become infected have risk factors for developing serious disease.

And therefore they may not be a candidate for one of these drugs.

Both companies told CNN in separate emails that the supply is expected to increase in 2021. This would happen as additional manufacturing resources "go up" (Regeneron) and "come online" (Eli Lilly).

In addition to Lilly and Regeneron's monoclonal antibody drugs, more than 70 different antibody treatments are being investigated for COVID-19, according to BIO, an association representing major biotech companies.

Difficulty producing monoclonal antibodies

There are several reasons why monoclonal antibodies are in short supply.

For one thing, unlike most drugs, which are made by combining specific chemical ingredients through a specific process, monoclonal antibodies are very large and complex molecules that are difficult to produce.

That is because they are what is known as biological.

Biologics are manufactured in a living system such as a microorganism or plant or animal cells.

“It's not like aspirin or just, you know, when you make a chemical (drug).

These are biological and it takes a lot of work to produce them, purify them and put them in a way that they can be delivered.

There are many steps along the way, ”said Gronvall.

Alternatives for manufacturing

According to Fouad Atouf, vice president of global biologics at US Pharmacopeia, a nonprofit organization that sets quality standards for drugs and related products, purification is "very labor intensive."

'But thanks to advances in science, there is specifically the recombinant DNA technology approach, whereby cell lines can be used as factories.

And now you can create synthetic copies of those antibodies, "he said.

In other words, cells can be genetically engineered and turned into factories to produce monoclonal antibodies.

Therefore, according to Atouf, the manufacturing capacity is limited.

"You can only do a few doses at a time."

Other obstacles

Another problem, he said, is the total volume: you need to give a patient a lot more monoclonal antibodies than, say, what you need to supply in the case of a vaccine or a pill.

A third issue, the one that worries him "a lot", is competition for raw materials.

Despite the challenges, Atouf said monoclonal antibodies have a lot of potential.

In addition to using them to treat people with mild COVID-19, he said there are studies looking to see if they can be administered prophylactically to prevent infection.

There is also research looking at whether they can be used against existing and emerging coronaviruses.

Access to monoclonal antibodies

There are a couple of additional hurdles that need to be overcome in order for people to receive the monoclonal antibodies in time to help them.

One is deciding where the limited supply of drugs is sent.

In order to ensure that access is as fair as possible, the government assigns the drugs weekly to each state within the framework of Operation Warp Speed.

It does so based on the number of confirmed COVID-19 cases in that state during the previous seven days.

State health departments are responsible for deciding how many doses to send to which health care facilities in their state.

AmerisourceBergen, a national distributor, delivers assigned medications directly to healthcare facilities overnight.

The challenge of delivering treatment

Another challenge with monoclonal antibodies is that they are not easy to administer.

They require an intravenous injection of one hour and an observation period of one hour in an outpatient setting.

Therefore, any center that is going to administer these drugs must organize to keep COVID-19 patients isolated from their other patients during the two-hour injection and monitoring process.

FDA's Dr. Janet Woodcock, director of the Center for Drug Evaluation and Research and leader of Operation Warp Speed, suggested during a news conference in early November that temporary injection centers may be a solution.

Another solution may be to partner with pharmacy chains.

HHS recently turned to CVS injection division Coram for a pilot program to deliver 1,000 doses of bamlanivimab to patients at home and in long-term care facilities.

The program launched on December 3 in seven cities and their surrounding communities.

It included Boston, Chicago, Cleveland, Los Angeles, Milwaukee, Minneapolis, and Tampa.

The role of patients in having monoclonal antibodies administered

It is also necessary to raise awareness among patients.

“We will all have to spread the word that high-risk people now have a therapeutic option as outpatients.

Up until this point, people have been told to stay home unless they become seriously ill, ”Woodcock said.

Steve Rudner, director of recruitment for the Vizient pharmacy network, a healthcare performance improvement company, agrees.

"As with many pharmaceutical agents or medications, the patient may not know if they are, in fact, a candidate for this," he said.

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«If you are a health provider and you have just confirmed a case of covid in a patient, and it falls into the high risk categories (…) it is your mission to ensure that the patient understands (…) 'here is a one hour injection that could prevent you from ending up in the hospital, "he said.

But patients also have a role, Rudner said.

“If a patient reads (an) article and says, 'Wait a second, maybe I'm in one of these high-risk categories.

If my doctor doesn't ask me about it, maybe I should ask him or her why I just tested positive and I don't want to be hospitalized, '”he said.

The FDA's Message to Patients

Hahn of the FDA echoed the sentiment.

“I would encourage anyone who might fall into the categories that I outlined to talk to their provider about this, because as an outpatient these (antibodies) can be given to people who are in high-risk populations.

We know that the clinical goal is to prevent hospitalization, ”Hahn said.

“God knows that healthcare systems are significantly overloaded right now.

So I encourage your viewers to ask vendors about this, ”he added.

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