For nearly two years now, creating a drug that can decrease hospitalizations and deaths caused by COVID-19 has been the primary pursuit of scientists across the world. In a positive step in that direction, Merck reported last month that its antiviral pill, molnupiravir, reduced the risk of hospitalization or death brought on by the SARS-CoV-2 virus by around 50 percent. Pushing these boundaries further, Pfizer announced on Friday that its investigational antiviral pill, Paxlovid, cuts the worst risks of the disease by 89 percent.
The American pharmaceutical giant made the announcement based on the interim analysis of the Phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) study. Within the overall population of the trial (through Day 28), no deaths were reported in patients who were given Paxlovid in comparison to 10 deaths (1.6 percent) recorded among patients receiving placebo.
"Today's news is a real game-changer in the global efforts to halt the devastation of this pandemic. These data suggest that our oral antiviral candidate, if approved or authorized by regulatory authorities, has the potential to save patients' lives, reduce the severity of COVID-19 infections, and eliminate up to nine out of ten hospitalizations," said Albert Bourla, Chairman and Chief Executive Officer, Pfizer, in a statement.
Inhibiting Replication of SARS-CoV-2
A combination of Pzifer's antiviral drug PF-07321332 and antiretroviral medication ritonavir, Paxlovid, is a protease inhibitor: a drug that prevents viral replication. PF-07321332 functions by blocking the action of a vital enzyme known as SARS-CoV-2-3CL protease. The novel coronavirus requires this enzyme for making copies of itself. PF-07321332 inhibits viral replication during a stage known as proteolysis, which takes place before the replication of viral RNA.
When administered along with a low dose of the ritonavir, which is primarily used to treat HIV, the breaking down or metabolism of PF-07321332is slowed down. The helps the compound remain active within the body for longer durations at higher concentrations, thereby, enabling effective combating of the SARS-CoV-2 virus.
Paxlovid has been particularly designed to be orally administered. It was done so in order to facilitate immediate prescription following the first indications of infection or after learning of exposure, which can potentially prevent patients from developing severe illness that can result in hospitalization or even death.
Reducing Worst Risks of COVID-19
Enrolment for the Phase 2/3 EPIC-HR study began in July 2021 after Phase 1 clinical trial showed promising results. EPIC-HR is a randomized and double-blind study of adult patients with COVID-19 who are non-hospitalized and are at an increased risk of who are at high risk of developing acute illness.
The interim analysis of this trial involving 1,219 high-risk COVID-19 patients, found that 0.8 percent (3/389) of patients who were given Paxlovid were hospitalized through Day 28 after randomization. No deaths were reported among these patients. In comparison, 7 percent (27/385) of patients who had received placebo were hospitalized, with seven succumbing to the infection.
Additionally, in patients treated with Paxlovid within five days following the onset of symptoms, similar reductions in COVID-19-related death or hospitalization were noted. One percent (6/607) of the patients receiving the drug were hospitalized through Day 28, and no deaths were reported. However, 6.7 percent (41/612) of the patients who were given placebo were hospitalized, with 10 subsequently dying.
Potential As A Treatment
Pfizer announced that it will stop further enrollment for the study based on recommendations from an independent Data Monitoring Committee along with those from the US Food and Drug Administration (FDA), owing to the immense efficacy shown by Paxlovid through these results. The company also intends to submit the data to FDA for the granting of a EUA (Emergency Use Authorization) at the earliest.
If Paxlovid recieves authorization or approval, it will become the first treatment of its kind (i.e) an oral antiviral designed specifically to inhibit the SARS-CoV-2-3CL protease. It could potentially become a more broadly prescribedat-home treatment. Having shown potent action against variants of concern (VOCs) of the SARS-CoV-2 virus and other coronaviruses, it also shows promise of becoming a therapeutic against different types of infections caused by multiple coronaviruses.
Appreciating the efforts of all those involve in the trial, Dr. Mikael Dolsten, Chief Scientific Officer and President, Worldwide Research, Development and Medical of Pfizer, concluded, "All of us at Pfizer are incredibly proud of our scientists, who designed and developed this molecule, working with the utmost urgency to help lessen the impact of this devastating disease on patients and their communities. We're thankful to all of the patients, investigators, and sites around the world who participated in this clinical trial, all with the common goal of bringing forth a breakthrough oral therapy to help combat COVID-19."