The monoclonal antibodies soon appeared in the pools of promising treatments against covid-19. His interest reached the zenith when Donald trump received the cocktail produced by the pharmaceutical company Regeneron. However, they fell into the background when, in early 2021, they were revealed to be ineffective against variants. This week, the results of a new clinical study have rekindled interest, albeit in moderation.
The British clinical trial Recovery has shared this week – in the form of non-peer-reviewed prepublication– the preliminary data of your study with the cocktail of two antibodies, casirivimab and imdevimabby Regeneron. The researchers observed that the mortality of the patients was reduced: the problem is that it decreased little and only in those unable to generate antibodies by themselves.
After analyzing the 28-day mortality in almost 10,000 patients admitted for coronavirus between September 2020 and May 2021, it was seen that among those who had not developed antibodies, 30% died, but only 24% of those who had received the cocktail
The scientists studied the 28-day mortality in nearly 10,000 patients entered by coronavirus between September 2020 and May 2021. Among those who had not developed antibodies, 30% died, but only 24% of those who had received the cocktail.
Furthermore, treated seronegative volunteers who left the hospital before 28 days did so somewhat earlier in the group that received the cocktail: 13 days instead of 17. 58% of those who received the antibodies were discharged at 28 days versus 64% of those who don’t.
“It is not a huge difference, the big difference is being seropositive,” the head of the Immunology service at the Ramón y Cajal Hospital explains to Sinc. Luisa Maria Villar. It refers to the fact that survival in patients who did develop antibodies was higher, whether or not they had taken the drug, and only 15% died. Furthermore, 75% of these patients left the hospital within 28 days.
The researchers found that when they analyzed all the patients together – whether they generated antibodies or not – these differences were not significant. The cocktail only works with a very specific group of patients: those who do not generate antibodies after an infection.
“The positive is that you do see a small improvement, although the difference is small,” he says. Sonia Zuniga, a researcher at the National Center for Biotechnology (CNB), more optimistic. He notes that no other monoclonal antibody treatment in critically hospitalized patients has worked so far, and attributes the success to being a cocktail that combines two different types. “That makes it more effective,” he clarifies.
The positive is that you do see a small improvement, even if the difference is small. No other monoclonal antibody treatment in critically hospitalized patients has worked so far. Combining two different types makes it more effective
Sonia Zuñiga, from the CNB
Villar believes that treatment is a little late and that it will not produce a “substantial change” in the management of patients. “In the current situation, what is needed is to vaccinate so that those who may or may not respond to immunization are protected by group immunity,” he says. For this reason, he thinks that it will remain as “something of the second or third line”.
“When we did not have vaccines it would have been more useful, but fortunately we are not there and we know that older people respond very well and are immunized,” says Villar. “For patients who have a correct immune response this does not contribute anything, only to those who do not develop antibodies nor cellular response ”.
He does admit that it could be used in those small, specific groups of patients. “It is one more tool that we have and that can help some immunosuppressed patient who becomes infected, but still the difference [en la supervivencia] it is little ”. The result is six lives saved for every 100 patients treated. “It is a possible therapy in some cases, but it is clear that it is not ‘the’ therapy,” adds Zúñiga.
The question of the variants … and the price
“These specific changes [de las variantes] have a dramatic influence on drugs that target specific binding sites, because if they are affected by a mutation, goodbye [al medicamento]”, The researcher from the Carlos III Health Institute (ISCIII) assured ElDiario.es, Vicente Mas, at the beginning of the year. Their fears were fulfilled, The Guardian revealed a month later: Monoclonal antibodies from Lilly, Regeneron and GlaxoSmithKline they failed totally or partially against one or more of the variants.
So how is it possible that the Regeneron cocktail is delivering positive results now? Zúñiga attributes it to the fact that it is precisely a cocktail with two different antibodies. “One seems to lose efficacy against the variants, but the other does not because it binds to another site. That is the grace, and that is why the combination continues to work ”, he assures.
To all this must be added the high price of Regeneron antibodies, which could exceed 2,000 euros per treatment, and the difficulty of their large-scale production.
Even so, the Spanish expert believes that there are pending doubts, such as what will happen to future variants and if in patients with a high viral load mutants could appear that “escape” these antibodies.
All this concern is due to the fact that these monoclonal treatments are based on a single type of antibodies – in this case, two – instead of the enormous variety that vaccines and natural infections generate.
To all this we must add the high price of Regeneron antibodies, which could exceed 2,000 euros per treatment, and the difficulty of its large-scale production. “The manufacture of monoclonal antibodies is cheaper today, but it is still expensive,” says Zúñiga. “Immunotherapy is used successfully against cancer, but widespread antiviral treatment is something else.”
In medical circles it is said that “if something has statistical significance, it does not imply that it has clinical significance”. Translated: that a drug produces a real effect does not always matter if it is small or has practical problems. In this case, those countries that can afford the Regeneron cocktail are likely to hardly need it. It is one more tool that could save some lives.
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