Paxlovid against Covid arrives late and efficacy against omicron is unclear, says study

The medicine Paxlovid, indicated for people with Covid at a high risk of complications, should arrive at Brazilian pharmacies soon, according to Pfizer, after authorization given by Anvisa (National Health Surveillance Agency) this past Monday (21).

Before, the drug had already been incorporated into the SUS by Conitec (National Commission for the Incorporation of Technologies in the Unified Health System). Another drug also approved for use against Covid is the antiviral molnupiravir, from MSD pharmaceuticals. In a statement on October 27th, Anvisa said it was waiting for more results to authorize its sale in pharmacies.

However, the evidence for the use of nirmatrelvir combined with ritonavir (the active compound in Paxlovid) at the current time of the pandemic has just been challenged in an article published in the scientific journal BMJ Evidence-Based Medicine (from the British Medical Journal group).

In the study, authors Todd Lee and Andrew Morris, from the Department of Medicine at McGill University, Quebec (Canada), and the University of Toronto, along with researchers Jason Pogue and Erin McCreary, from the University of Michigan and the School of Medicine of Pittsburgh (USA), state that, based on the most recent evidence, the benefit of using nirmatrelvir and ritonavir for immunocompetent patients vaccinated and/or recovered from Covid is uncertain.

The scientific research, which reviewed the available literature, listed the main findings about Paxlovid and its effectiveness against hospitalizations and deaths. The first randomized, double-blind clinical trial, conducted by Pfizer, included 2,246 participants, of whom half received a placebo and half the drug. Only patients with a high risk of progression to severe disease and over 18 years of age who were not hospitalized were considered.

The conclusion of the study was that Paxlovid prevented one hospitalization in every 18 cases, but even this benefit was found in the context of circulation of the more aggressive delta variant.

The authors reworked the analysis of the Pfizer study in the context of omicron circulation and its subvariants. Considering a risk of hospitalization with omicron approximately 40% lower than that of delta, the expectation was that the drug would prevent more hospitalizations, but the result obtained was one hospitalization avoided in every 42 cases.

Another most important point is that protection in vaccinated individuals who used the drug is still unknown. As vaccination was a determining factor in reducing hospitalizations and deaths, the researchers expected to find a greater benefit also in the use of the drug by these individuals, which was not found, since vaccinated people (including boosters) become infected with omicron, but they rarely progress to hospitalization and death.

Finally, the scientists consider that, if there is currently no obvious benefit from using Paxlovid to avoid hospitalization and death, the resolution of symptoms in a few days could be a possible use, thus improving the clinical picture of the disease. But, as this was not an outcome sought in the pharmaceutical’s clinical trials so far, there is no such indication for use, and the benefit remains unknown.

For the authors, the medicine, like other antivirals, has its value, but the approval of agencies such as the American FDA (Food and Drugs Administration) at the current time of the pandemic did not consider the best available evidence. The researchers also point out that the high cost of these antiviral treatments should be considered when public health policies are considered.

The article says that the American government spent about US$ 100 billion (about R$ 557 billion) with therapies with “low value” of medical evidence, that is, treatments with no indication for use or offered to patients who do not correspond to the criteria defined in the study.

In Brazil, the difficult access to medicines against Covid has been criticized by many specialists, especially in times of the pandemic with a greater number of cases and, consequently, hospitalizations and deaths.

More studies are needed to indicate a possible benefit of antivirals in all types of patients and against new variants. The study authors conclude, however, that the coronavirus is a virus that will remain in circulation for a long time, and it seems “reasonable to make choices about how we choose and prioritize therapies so as not to repeat the choices of the past”.