Peace, love and Covid… By choosing to call its anti-SARS-CoV-2 treatment “Paxlovid”, the Pfizer laboratory has not skimped on hyperbole. And for good reason: on paper, it looks like a miracle drug. Taken morning and evening for five days, nearly 90% of patients avoid having a serious form after an infection. Enough to change the course of the epidemic, by easing the burden on hospitals. But if the arrival by the end of the month in pharmacies of this first oral antiviral remains good news, the reality could, as always, prove to be a little more complex.
In an opinion issued this Friday, the High Authority for Health gave its authorization for early access to this drug for adults who present a high risk of serious forms of Covid-19: “In the context of the predominance of the Omicron variant, and despite its lesser severity, the need for treatment for fragile patients affected by Covid-19 is not satisfied”, justify its experts. This concerns patients who are severely immunocompromised or who have a “very high risk” pathology, such as those suffering from cancer and treated with chemotherapy, or even people with severe chronic kidney disease and on dialysis. France has pre-ordered 500,000 treatments, including a first delivery “of several thousand doses” to arrive by the end of January.
Authorized in December by the European Medicines Agency, Paxlovid could present a solution for some of the most fragile patients, while most of the treatments currently on the market have become useless in the face of Omicron. Its mode of action allows it to remain effective against this variant. Because, this time, this tablet does not target the Spike protein, whose mutations lead to a decrease in the effectiveness of vaccines, it acts by blocking the protease, an enzyme necessary for the replication of the virus in the heart of our cells. “This part has so far remained the same regardless of the variant”, notes Bruno Canard, coronavirus specialist and research director at the CNRS. A mutation could always occur there, but, for the moment, Omicron has not deviated from this rule.
On the other hand, the very strong effectiveness observed during clinical trials could prove to be less in real life. Because Paxlovid has been tested on patients with fairly common comorbidities (obesity, diabetes, etc.). But now doctors will mainly offer it to immunocompromised patients in whom vaccination does not generate immune defenses. However, these patients have still not been included in clinical trials. And for good reason: they take medications that can be disrupted by one of the two components of Paxlovid, ritonavir.
The patient target could be reduced
“This molecule interacts with many other pharmaceutical products. But the population at risk of a serious form is precisely those who suffer from chronic diseases, and who take a lot of drugs. Its target could therefore be quite small”, notes Professor Mathieu Molimard, Head of the Pharmacology Department at the Bordeaux University Hospital Center.
And in fact, in its opinion, the HAS enacts many contraindications and precautions for use of this drug. The antiviral is, for example, contraindicated in people with severe hepatic insufficiency or severe renal insufficiency, or even in pregnant women. “It is up to the doctor to assess with his patient the medicinal contraindications to the use of Paxlovid”, underlines the HAS. The French Society of Pharmacology and Therapeutics (SFPT) for its part is already anticipating the needs of general practitioners, who will be on the front line for prescriptions. “It will not be white or black, we will specify which treatments can be interrupted, which ones to continue with reduced doses, etc.”, indicates Pr. Molimard, also a member of the SFPT. A prescription assistance tool should also see the light of day.
Awareness campaign needed
Another pitfall: for it to be effective, Paxlovid must be administered within five days after contamination or the onset of symptoms. A real challenge as the epidemic saturates appointments for tests and GP surgeries. In Israel, where this drug has been distributed for three weeks, the difficulties quickly appeared. In this country where the virus also circulates a lot, just under 3000 patients only were able to benefit from it. In addition to the logistical problems of transporting the drug, there was the fear of possible side effects. According to the health organization Maccabi Healthcare Services, up to 25% of the patients concerned would refuse this treatment…
“We plead for the public authorities to quickly launch a communication campaign to make those concerned aware of the arrival of this drug, but also of its constraints, and the importance of being tested quickly”, underlines Jean-Paul Ortiz. , the president of the Confederation of French medical unions. So many possible snags that could tarnish the luster of a not yet quite miraculous pill.