UPDATE: Pfizer's oral COVID-19 antiviral cuts hospitalization, death by 89%, sending team barreling to FDA

Pfizer’s oral COVID-19 antiviral Paxlovid has cut the risk of hospitalization or death by 89% in a late-phase trial, prompting the Big Pharma to stop the study and race to seek emergency use authorization from the FDA.

Merck showed oral antivirals can make a difference in COVID-19 around one month ago, presenting late-phase data showing its candidate halved the risk of hospitalization and death. Comparing results from different studies can give a misleading impression, but, on the surface, it appears Pfizer may have reset expectations of efficacy for oral antivirals.

Pfizer’s phase 2/3 trial randomized non-hospitalized adult COVID-19 patients who were at high risk of progressing to severe illness to receive placebo or Paxlovid, a combination of the protease inhibitors PF-07321332 and ritonavir. The efficacy analysis is based on 1,219 patients.

There were six hospitalizations and no deaths among the 607 patients who received Paxlovid within five days of symptom onset, compared to 41 hospitalizations and 10 deaths in the placebo cohort. The rates of hospitalization or death in the Paxlovid and control arms were 1% and 6.7%, respectively, resulting in a risk reduction of 85%. 

RELATED: Pfizer's oral COVID-19 antiviral gets rolling in phase 2/3 trial

Pfizer used data on patients who were treated within three days of symptom onset as the headline finding in its press release. In that subpopulation, the rates of hospitalization or death in the Paxlovid and control groups were 0.8% and 7%, respectively, resulting in a risk reduction of 89%. Merck’s 50% reduction was seen in patients who were randomized within five days of symptom onset. 

The delivery of data on Merck’s molnupiravir and Pfizer’s Paxlovid suggests countries could soon have access to medicines that patients can take orally after receiving a COVID-19 diagnosis to significantly lower their risk of the worst outcomes. Neither trial had seen a death in the treatment group at the time of the interim analyses.

Like Merck, Pfizer excluded people vaccinated against COVID-19 from its late-phase study. Pfizer has included a cohort of vaccinated patients with acute breakthrough symptomatic COVID-19 and risk factors for severe illness in a second, ongoing phase 2/3 assessment of Paxlovid. 

Pfizer had safety data on 1,881 patients at the time of the interim analysis. The Big Pharma is yet to share a detailed look at the data, but the headline findings are encouraging, with fewer serious adverse events and discontinuations of study drug due to adverse events in the Paxlovid arm than in the control cohort. As a protease inhibitor, Paxlovid is free from the theoretical DNA-alteration risk tied to the mechanism of action of Merck’s molnupiravir. 

RELATED: Merck seeks FDA nod for COVID antiviral 10 days after data drop

Armed with the data, Pfizer is now racing to prepare a submission for emergency use authorization. Merck got its submission to the FDA around 10 days after publicly reporting the data, leading to the scheduling of a Nov. 30 advisory committee meeting to discuss molnupiravir.

'Pre-COVID normalcy'

Pfizer has already staked out its claim as one of the leaders in the COVID-19 vaccine market, but the antiviral could open up an entire franchise for the New York Big Pharma. Sales expectations for the vaccine, called Comirnaty, were bumped up to $36 billion from a prior projection of $33.5 billion earlier this week thanks to the approval of boosters and the FDA nod for children aged 5-11.

RBC Capital Markets said Pfizer's data "may mark a turning point in the pandemic" and a return to "pre-COVID normalcy."

Mizuho analysts did not have sales predictions for the antiviral just yet, but the firm anticipates the treatment will "complement, not cannibalize" vaccine sales. Physicians will be able to use the antiviral as a tool for treating severe illness—especially in those who remain unvaccinated. Those who intend to get vaccinated will still do so. 

RELATED: Merck and Ridgeback's COVID-19 oral antiviral molnupiravir joins the pandemic response with U.K. nod

Merck's molnupiravir has a slight edge over Paxlovid in terms of ease of use, and it's already authorized in the U.K. with a review underway in the U.S. Pfizer's treatment must be administered in combination with ritonavir to help slow down its metabolism, while molnupiravir is a single drug. But if Pfizer can beat on efficacy in terms of reducing hospitalizations and safety, doctors may reach for Paxlovid over molnupiravir. No deaths were seen in either Merck or Pfizer's trials.

"Regardless, we see a large commercial opportunity for both products in the near-term at least given the global demand that we expect for oral treatment options and the likely stockpiling we would expect for both drugs," Mizuho said. 

RBC noted two other promising antivirals in development, Shionogi's once-daily S-217622 and Enanta Pharmaceuticals' EDP-235, both of which are oral protease inhibitors. With Pfizer offering up "such striking results, there may be little room for improvement" for Enanta, according to RBC. 

Editor's note: This story was updated at 9:16 a.m. ET on Nov. 5 to add analyst commentary.