On the one hand a mix of monoclonal antibodies, on the other a pill to be taken by mouth: according to the studies available, the two treatments are 50% effective in preventing severe forms of the disease, but how can they really be used?
Earlier this week, news of the US pharmaceutical company’s request arrived Merck to the Food and Drug Administration (FDA), the body that regulates medicines in the United States, to approve with emergency authorization the use of his anti Covid-19 pill molnupiravir. And in a few hours the Anglo-Swedish language too AstraZeneca posted an update on their medication AZD7442 based on monoclonal antibodies, announcing (even before there is a scientific publication to confirm it) the results in phase 3 of experimentation, in addition to having forwarded a similar request for emergency authorization to the Fda.
Two news that, although concerning very different pharmacological solutions, mark a further step towards the arrival on the market of new therapies against the coronavirus Sars-Cov-2. And which would seem to have a quantitative factor in common: in both cases, in fact, the medicines have been shown to have in the first place an effectiveness close to 50% in preventing the severe forms (including mortality) of Covid-19, provided they are administered sufficiently precocious. But let’s go in order.
The latest on AstraZeneca monoclonal antibodies
The drug AZD7442 it is certainly not one new entry in the panorama of potential therapies against Covid-19. On Wired and in many newspapers it was already mentioned a year ago, in October 2020, and in February of this year it had already started Phase 3 clinical trial called Tackle. Study that, at least according to the company’s public announcements, it would be time successfully concluded, making it plausible an imminent green light from the various regulatory agencies, starting with the US one.
From a more technical-scientific point of view, AZD7442 is a solution to be administered by intramuscular injection consisting of a combination of two different monoclonal antibodies: the tixagevimab (in initials, AZD8895) and the cilgavimab (AZD1061). These, also called long-acting antibodies (Laab, long-acting antibodies), act directly on the proteina spike del coronavirus Sars-Cov-2 inhibiting its ability to replication inside the human body, and are obtained through an engineering process of B lymphocytes of patients recovered from Covid-19.
According to the data obtained from a group of approx 900 fragile patients involved in the trial, AZD7442 (administered in addition to other standard therapies) is capable of halving the mortality of infected patients and also halves the frequency of severe and very serious cases. All this if administered early in the early stages of the disease, and in any case no later than 7 days from the appearance of the first symptoms.
Of course that of AstraZeneca is not the only existing formulation based on monoclonal antibodies. For example, there are also those developed by Regeneron and Eli Lilly, based on different monoclonal antibodies. The difference, at least as stated by the company itself, is that AZD7442 would seem to be promising not only to treat patients who are already positive, but also how pre-exposure prophylaxis to the virus, since once injected the antibodies would remain in circulation for at least 9 months. On the efficacy for antiviral prophylaxis, however, there are no supporting studies and the possible marketing authorization that should arrive would only concern the use for the initial stages of the disease.
Merck’s anti-Covid-19 pill
Very different in administration, since it is one tablet to be taken by mouth, is the ssolution proposed by Merck (better known in Italy as Msd) and Ridgeback Biotherapeutics, again to intervene in the early stages of the disease. Based on a Phase 3 clinical study conducted on nearly 800 fragile patients, the antiviral pill molnupiravir would be able to halve the probability of death and to get to severe or very serious forms of Covid-19. Always assuming that the remedy is taken when the disease still has forms “Moderate to mild”. A result that has led to an acceleration of the path to obtain authorization, and which could mark an important step forward in reducing the impact of the pandemic on national health systems.
Confident in the successful completion of the emergency approval process, Merck also announced that it has already initiated the mass production of the drug (assuming the economic risk), aiming by the end of this year to have enough pills to cover the entire course of treatment for 10 million patients. The treatment cycle requires the small capsules (brown in color) to be taken twice a day for 5 days, for a total of 10 total administrations. The production between now and December therefore amounts to 100 million capsules, and 17 million would have already been bought by the US government, which it paid for 1.2 billion dollars.
The reason why there has been great anticipation for molnupiravir lies not only in the ease of administration. Once authorized, it would be the first drug to work directly against the Sars-Cov-2 virus, unlike others in current use (such as remdesivir) which are less specific and not very effective. It would also pave the way for the use of combination therapies with other drugs, allowing an even higher overall efficacy on the patient.
Covid-19 drugs and vaccines
Of course the pill developed by Merck it is not a direct competitor vaccines, since it would be administered in the early stages of the disease and not as a drug for prophylaxis. Slightly different, however, is the discourse for the formulations based on monoclonal antibodies, which – if they were also authorized for use as a prevention therapy – could be a valid alternative to vaccines for i immunosuppressed patients, i.e. they are unable to develop sufficient antibodies after vaccine administration.
There is no doubt, however, that the vaccines they will remain the main strategy for fighting the pandemic, for at least a couple of reasons. In addition toexcellent effectiveness that the Pfizer and Moderna vaccines currently in use in our country guarantee in preventing severe forms of the disease, there are also important reasons of character economic. Monoclonal antibody-based therapies have a cost of orders of magnitude higher than vaccines, therefore it would not be feasible at the time of using them as a mass drug, even if they were authorized for prophylaxis. While for post-infection use (beyond economic issues) they will likely represent one more opportunity to reduce the number of hospitalizations and deaths related to Covid-19, but it goes without saying that the best solution can only be prevent infection from the beginning.