The Paxlovid is making a lot of noise in France, at the announcement of its imminent arrival at the end of this month of January with our neighbors, and which will be produced partly on their territory.
In Belgium, this combination of two molecules produced by the American firm Pfizer is not yet available. The European Medicines Agency has not yet given its marketing authorization, unlike the American regulatory authority, the FDA. She has, however, allowed its use in an emergency, on December 16th. Countries are free to acquire them for these exceptional situations.
What mechanism?
Paxlovid slows the replication of the virus in people who are already infected. It comes in the form of separate tablets comprising two molecules: nirmatrelvir (a new molecule) slows down an enzyme necessary for this viral replication, and ritonavir (an antiretroviral already used against HIV, the AIDS virus) slows down the destruction of nirmatrelvir . It can also slow down the destruction of other drugs taken by a patient, hence a certain risk of toxicity.
For which patient?
Paxlovid is indicated for patients at risk of developing a severe form of Covid-19. Treatment should be started within 5 days of the first symptoms of confirmed Covid-19.
When will he be in Belgium?
No date has yet been announced. The drug is not yet available in our country. The “Covid Therapeutics” task force, which provides treatment recommendations, issued a favorable opinion on the purchase of 10,000 doses of this drug. However, the contract with the Pfizer firm has not yet been signed.
It will be used according to a specific protocol, in order to collect additional data on efficacy and safety.
What efficiency?
A phase 3 trial took place on 2246 patients at risk, for whom obesity was the main risk factor. The average age of the patients was around 45 years old and they were unvaccinated. There were also few old people and the Omicron variant was not yet in circulation. The results show a reduction in hospitalizations in these patients from 6.3% to 0.8%. The firm communicated an 89% reduction in the risk of hospitalization or death compared to placebo in high-risk non-hospitalized adults with Covid-19.
A criterion for evaluating the effectiveness of a drug is what is called the “number of patients to be treated”, in English the NNT: for Paxlovid, 18 patients at risk must be treated to avoid hospitalization.
Which mode of administration?
Will Paxlovid be available directly from the pharmacy for the patient? It’s not decided yet. It will certainly be distributed in a controlled way, given the small number of doses available.
The patient should take 2 tablets of 150 mg of nirmatrelvir and 1 tablet of 100 mg of ritonavir, twice a day, for 5 days.
Contraindications and side effects
Patients who are pregnant or may become pregnant should not take this treatment which is not recommended for them, as explained by the European Medicines Agency. Breast-feeding should also be discontinued during treatment.
The most common side effects are taste disturbance, diarrhea and nausea.
And the other treatments?
The “Covid therapeutics” Task Force has issued additional opinions on two other treatments. Molnupiravir, sold under the trade name Lagevrio by the firm Merck (MSD), and sotrovimab, sold under the trade name Xevudy by the firm GSK.
– Lagevrio (molnupiravir – Merck / MSD)
This antiviral has not yet received authorization from the European Medicines Agency (EMA), but is authorized in the United States and the United Kingdom. The EMA has, however, issued a opinion authorizing Member States to use it urgently, to treat adults with confirmed Covid-19 who do not require supplemental oxygen and who are at high risk of developing severe Covid.
As with Paxlovid, treatment with Lagevrio should be started within 5 days of the first symptoms.
The Lagevrio has another mode of action: it introduces errors in the replication of viral RNA. The criterion of the number of patients to be treated is less efficient: to avoid hospitalization, 33 patients at risk must be treated.
A phase 3 trial was carried out with 1433 patients at risk, here too, before the Omicron era. The interim results of the clinical study showed an absolute risk reduction of 6.8% and a relative risk reduction of 48% in hospitalization and mortality in the group treated with Lagevrio compared to the placebo group.
However, on November 26, an update to the results of the phase 3 study was published, reducing these results, and containing data from all patients involved. The absolute and relative risk reductions were revised to 3% and 30% respectively.
In France, the Haute Autorité de Santé has therefore decided against authorizing the early access use of this antiviral.
Belgium, on the other hand, has purchased 10,000 doses for 2022. Controlled distribution will take place from this month of January, with data collection, in the event of epidemic peaks in nursing homes.
Lagevrio also cannot be used during pregnancy or before the age of 18. Questions remain about the mutagenicity of this antiviral, namely its ability to increase the rate of mutations in the virus.
– Le Xevudy (sotrovimab – GSK)
Here, we are in another category of treatment, which is administered not orally, but intravenously. These are monoclonal antibodies. The treatment was aApproved by the European Medicines Agency on December 16 last.
The Belgian Task Force has issued an opinion recommending a purchase of 20,000 doses, to be reassessed afterwards, due to the risk of an increase in demand in the coming months, given the high circulation of the Omicron variant. It is one of the rare monoclonal antibodies which seems to retain a certain reactivity (in vitro) against this variant.
Xevudy has been used since mid-November 2021 in immunocompromised hospitalized patients. It is administered by single intravenous infusion, within 5 days of the onset of symptoms, in patients at risk.
The number of patients to be treated is intermediate, between Paxlovid and Lagevrio: 22 patients at risk must be treated to avoid hospitalization. Phase 3 clinical trials with 1057 at-risk patients (non-Omicron period) showed a reduction in the absolute risk of hospitalizations from 5.6% to 1%.