COVID MEDICINE. Paxlovid from the Pfizer laboratory, the first Covid treatment accessible in town, has just been authorized by the European Medicines Agency. It should be available at the end of January, according to HAS. Composition, effectiveness, against Omicron, principle, side effects: discovery.
[Mise à jour le 27 janvier 2022 à 17h36] Green light for Paxlovid, a treatment made by the laboratory Pfizer to be administered orally (in tablets) at the first signs of Covid infection in order to avoid serious forms. In a statement of January 27, 2022, the European Medicines Agency (EMA) announced the conditional marketing authorization of Paxlovid for the treatment of Covid-19, in adults who do not require supplemental oxygen and who are at increased risk of severe form. In France, on January 21, the High Authority of Health authorized this drug in early access for adults with Covid-19 not requiring oxygen therapy and at high risk of progression to a severe form of the disease. “This early access authorization is granted following the opinion of the ANSM having concluded on the basis of the evaluation of the preclinical and clinical data available at a favorable risk/benefit ratio presumed in the therapeutic indication” argues the HAS. It would reduce 85% the risk of having a severe form of Covid. The Paxlovid is the first treatment for Covid-19 which will be accessible in town and can be prescribed by general practitioners. Its mechanism of action “gives hope of sustained efficacy on the different variants, including Omicron”. This drug treatment comes in addition to vaccination “as a substitute”. “More broadly the implementation of anti-Covid-19 treatments, does not exempt patients from respecting barrier measures and physical distancing“ specifies the authority. The Paxlovid should be available in pharmacies “from the end of January” according to HAS. The HAS recommends setting up a follow-up cohort for this anti-Covid-19 treatmentwhich will aim to assess the immuno-virological and clinical efficacy in various groups of patients and to monitor the risk of emergence of potential resistance, particularly in immunocompromised patients. The HAS also hopes that clinical trials on this combination treatment can be set up soon. What is the composition Paxlovid? What is its function ? Its effectiveness against Covid? Its side effects?
What is Paxlovid?
The American pharmaceutical company Pfizer developed antiviral treatment, marketed under the name of Paxlovid made up of nirmatrelvir and of ritonavir. It comes in the form of tablets to be taken as soon as possible after the positive diagnosis for Covid-19 and maximum within five days following the onset of symptoms. This treatment targets the enzyme necessary for viral replication, the 3C-like protease, and by inhibiting its action, it blocks the replication of SARS-CoV-2 in the body.
When will Paxlovid be available in France?
The Paxlovid is the first treatment for Covid-19 which will be accessible in town and can be prescribed by general practitioners. According to the HAS publication, it will be available from the end of January. On January 27, the European Medicines Agency announces the conditional marketing authorization for Paxlovid. Conditional Marketing Authorization (AMC) is used as an expedited authorization procedure to expedite drug approval during health emergencies. This generally concerns drugs that meet an unmet medical need on the basis of less complete data than those normally required. This occurs if the benefit of the immediate availability of a drug to patients outweighs the risk inherent in the fact that all the data are not yet available.
How effective is it against Covid and against Omicron?
According to the High Authority for Health, Paxlovid “retains antiviral activity on the different variants“. “The data available to assess the efficacy of this treatment have demonstrated a reduction in the risk of progression to a severe form of Covid-19 (hospitalization or death) by approximately 85.2% (EPIC-HR study) after its administration.” Against Omicron, the mechanism of action of Paxlovid “gives hope of sustained efficacy” specifies the HAS. Preliminary in vitro data indeed suggest that the variants of concern currently circulating are susceptible to treatment.
For who ?
The HAS recommends prescribing Paxlovid for adult patients at risk of a severe form of Covid-19, i.e.:
- regardless of their age and their vaccination status, adult patients who are severely immunocompromised or who have a pathology at very high risk of a serious form (in particular cancers undergoing treatment, polypathologies, trisomy 21 or certain rare diseases;
- patients over the age of 65 with risk factors for developing serious forms (diabetes, obesity, chronic renal failure, heart failure, arterial hypertension, respiratory failure, etc.), in particular when these people are not or are not fully vaccinated.
What is the composition of Paxlovid?
Paxlovid is made up of two molecules. The first one PF-07321332 is the active agent that prevents the virus protein from replicating. The second is ritonavir, a protease inhibitor, normally used for the treatment of HIV infections. “HIV is not related to coronaviruses and the replication of its genetic material occurs through a different mechanism. But it produces him too a poly-protein that must be cut 9 times per a protease to form new viral particles“, Explain an article published in the scientific journal Medicine Science in June 2020.
Paxlovid would prevent the coronavirus protease from replicating.
A protease is a virus-specific enzyme which acts on viral proteins to promote the replication of the virus. To stop the replication of a virus, it is therefore necessary to reduce or prevent the protease from acting. Coronaviruses have two proteases, one of which is called SARS-CoV-2, 3CL. It is on this protease that the oral treatment Paxlovid acts.
What is the dosage of Paxlovid?
It comes in the form of tablets (2 tablets nirmatrelvir PF-07321332 and 1 tablet ritonavir) to be taken by mouth twice a day for five days.
What are the side effects ?
Among the patients who participated in thePfizer study published in November 2021 and who received Paxlovid, 1.7% experienced serious adverse events and had to stop treatment. The active substance contained in this medication, ritonavir, can indeed cause side effects such as:
- diarrhea,
- nausea and vomiting
- abdominal pain
- sore throat or cough,
- headaches and dizziness
- skin rashes and itching
- disturbances in the metabolism of sugars and fats with abnormal fat redistribution observed after several months of treatment (called lipodystrophy)
- toxicity to the liver (increase in transaminases) and the pancreas.
What are the contraindications of Paxlovid?
The antiviral is contraindicated in people with severe hepatic insufficiency or severe renal insufficiency. Dosage adjustment is necessary in patients with moderate renal impairment. Furthermore, it is not recommended to use Paxlovid during pregnancy. HAS recalls that in the event of a contraindication, the use of the monoclonal antibody Xevudy is possible as a cure. In addition, prophylactic treatment with monoclonal antibodies Evusheld must be offered to eligible patients.
What is the price ?
The price of the Paxlovid pill is not known. Nevertheless, Pfizer announced, in its press release, tiered pricing based on each country’s income level in order to guarantee equitable access to all and an affordable price. In other words, high- and upper-middle-income countries will pay more than low-income countries.
Sources
– Covid-19: early access granted to Paxlovid® as a curative treatment. HAS. Press release January 21, 2022.
– PFIZER’S NOVEL COVID-19 ORAL ANTIVIRAL TREATMENT CANDIDATE REDUCED RISK OF HOSPITALIZATION OR DEATH BY 89% IN INTERIM ANALYSIS OF PHASE 2/3 EPIC-HR STUDY, November 5, 2021.
– Targeting the major protease of SARS-CoV-2 to manufacture an effective drug against this coronavirus, Medicine Science, June 2020.