Antiviral pill cuts risk of hospitalisation and death due to covid

BarcelonaPharmaceutical companies Merck, known as MSD, and Ridgeback Biotherapeutics announced on Friday that their experimental antiviral pill, molnupiravir, reduces the risk of hospitalisation by about 50% among people infected with covid and virtually eliminates the risk of death. Results from phase 3 trials – which test whether the drug is effective – show that only 7.3% of patients who received the drug were hospitalised in the following 29 days, compared to the 14.1% of those on placebo. In addition, no fatalities were recorded among the patients who were treated with the drug, while eight of the patients who did not receive it eventually died.

Molnupiravir is an orally administered broad-spectrum drug that interferes with viral replication of viral RNA. Specifically, it prevents the lethal accumulation of enzymes and prevents the pathogen from continuing to reproduce inside the body. "This is very good news because until now we had made great progress in vaccines but not in specific treatments against covid. Moreover, this drug has a number of advantages: it is a pill that is taken twice a day for five days, it is cheap and easy to produce and a priori effective against future mutations because its target is the enzyme and not the so-called S protein (a.k.a. spike), which is much more mutable, which vaccines target", explains Adelaida Sarukhan, immunologist and expert in zoonotic diseases at the Barcelona Institute for Global Health (ISGlobal)

With vaccination campaigns underway around the world, albeit with great differences depending on countries' access to vials, the missing piece in the fight against covid is a specific treatment. Molnupiravir is not the first drug to generate hope against severe covid, but it is the most promising. Several antivirals already on the market have been studied and tested in recent months and repurposed against SARS-CoV-2, such as remdesivir, which was developed to treat Ebola virus and was tested with unconvincing results. Common corticosteroids such as dexamethasone have also been used for critically ill patients, and monoclonal antibodies capable of blocking virus entry and cell infection have been tried. The latter, however, are very expensive and difficult to produce.

Phase 3 trials for molnupiravir were carried out in twenty countries around the world and found a very low incidence of adverse effects, even lower than in the placebo group: 35% of those who received molnupiravir experienced some kind of side effect compared to 40% of those who received the placebo drug. In addition, the study includes viral sequencing of approximately 40% of participants and it has been shown that the efficacy of this antiviral is not only high against the Delta variant, but also against Gamma and Mu, considered mutations of interest. Nevertheless, Sarukhan urges caution until the announced results are reviewed, although she admits that a priori they are reliable and favourable.

Useful for people at risk of complications

Molnupiravir was created by Drug Innovations at Emory (DRIVE), a non-profit biotechnology company wholly owned by Emory University (USA), but Merck, in collaboration with Ridgeback Biotherapeutics, is exploiting it. "The fact that it already exists allows us to go faster and jump the first phases of the trials, since safety is already proven and guaranteed," says Sarukhan. However, this pill is complementary to vaccination, it will not replace it. "Having this tool does not mean that we stop vaccinating. However, vaccines are not perfect and some vaccinees may become ill, regardless of age, and this drug will be very useful for people who are at risk of suffering complications," the immunologist explains.

Although it is still too early to define which groups can be targeted, it would be logical to think that the over-60s and people who have a contraindication to the vaccine (for example, are allergic to any of the components) would be good candidates. It is also unclear what would be the optimal period of administration, although the study with 775 people was conducted in infected people five days after they developed symptoms and who had not been vaccinated. "What is clear is that for it to be useful it has to be administered preventively, before they get worse, and in people who have at least one risk factor associated with a bad evolution," says Sarukhan. Risk factors include obesity, chronic heart and lung disease, and type II diabetes.

Based on the positive trial results, the two drug companies behind it plan to submit an application for emergency use authorisation in the United States "as soon as possible" and have announced that they will submit marketing requests to other regulatory agencies around the world. The U.S. government announced last June the purchase of 1.7 million doses of this experimental treatment for $1.2bn (about €1bn) if the agency authorises it

"More tools and treatments are urgently needed to fight the pandemic, which has become one of the leading causes of death and continues to profoundly affect patients, families and societies and testing health care systems around the world," said Merck CEO and president, Robert M. Davis. In this sense, he stressed that trial results invite "optimism": "Molnupiravir can become an important drug as part of the global effort to fight the pandemic," he added.

Merck had also participated in the scientific race for the vaccine but its prototype – monodose and using the attenuated virus, the most classic type – failed: the first data from clinical trials showed a "lower" immune response than expected and even lower than the antibodies of those already infected. The pharmaceutical giant went so far as to call the results of its trials "disappointing".