Paxlovid (PF-07321332/ritonavir) for outpatient COVID-19:

EPIC-HR Trial
eddyjoemd.com/paxlovid/

eddyjoemd (Eddy J. Gutierrez MD) November 5, 2021

I have mentioned that I am not a fan of medicine by press release, most recently when
covering molnupiravir. Earlier today, 11/5/21, Pfizer put out a press release with the headline
in all caps “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”. It certainly caught my eye that they called the the EPIC-HR
study but EPIC stands for Evaluation of Protease Inhibition for COVID-19 in High-Risk
Patients. Pfizer is calling its medication Paxlovid with the study drug name of PF-
07321332/ritonavir. Those of us with medicine training will recognize the ritonavir component
as this is a medication used in HIV and has been around for decades. None of this is medical
advice. I am an ICU physician and not a primary care/outpatient physician who will ever
prescribe Paxlovid.

What type of trial was EPIC-HR?

The EPIC-HR trial is a randomized, double-blind study of non-hospitalized adult patients with
COVID-19, who are at high risk of progressing to severe illness. This is a phase 2/3 study.
Per clinicaltrials.gov, they are attempting to enroll 3000 patients and these data are from the
interim analysis of 1219 patients. The key here for my practice is non-hospitalized. Families,
please don’t call me in the ICU and ask for this medication. There’s no data that it works
there.

What is the regimen of Paxlovid?

Paxlovid (PF-07321332/ritonavir) is to be provided orally every 12 hours for 5 days (10 doses
total).

What did the EPIC-HR trial find regarding Paxlovid?

Their primary endpoint, as defined on clinicaltrials.gov was “Proportion of participants with

COVID-19 related hospitalization or death from any cause”. The study found an 89%
reduction in risk of COVID-19-related hospitalization or death from any cause compared to
placebo in patients treated within three days of symptom onset.

Meeting the primary endpoint we had 0.8% of patients in the Paxlovid group (3/389
hospitalized with no deaths) versus 7.0% of patients in the placebo group (27/385
hospitalized with 7 subsequent deaths; p<0.0001). Although these numbers sound extremely

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promising, when you plug in these numbers into your number needed to treat calculator, you
find that you have to treat 16.1 patients to avoid one hospitalization or death from any cause.

What if treatment is started within 5 days rather than 3?

If patients were started on therapy within 5 days of symptom onset, the NNT gets a bit worse
at 17.5 because in this subgroup, 1% of the Paxlovid group met the primary endpoint vs.
6.7% in the placebo group.

But did anyone die?

In the Paxlovid group, no one died. These are high-risk patients (although we don’t know
how high-risk) as a quick reminder. 1.6% of patients died in the placebo group at day 28. The
numbers are too small to be academically honest and provide an accurate NNT but, just for
fun, the NNT here is 62.5. This get you thinking a bit about the overall mortality rate of all
this. If high-risk patients have a mortality rate of 1.6%, what does that mean for other
populations? I’ll leave that for you to decide risk tolerance.

Were there any adverse effects to Paxlovid?

They reviewed 1881 patients for this component. Adverse effects were mostly mild and
noted in 19% of the Paxlovid group and 21% of the placebo group. Patient receiving Paxlovid
also did better in the those treatment-emergent adverse events with fewer serious adverse
events (1.7% vs. 6.6%). They noted that patients bailed from the trial more often in the
placebo group (4.1%) rather than the paxlovid group (2.1%). In my opinion, this means the
adverse effects from COVID were worse than those of the medication.

How much will the Paxlovid regimen cost?

This is NOT listed on the press release nor on any reliable source so here, more than
anywhere else, you should not trust me. The number that I have read on various media
outlets, and I don’t trust media outlets, is $700 a regimen as Pfizer was targeting the same
price as Molnupiravir. If we do math here, and know that we have to treat 16.1 people to
keep one person out of the hospital, this means that we will be spending over $11,000 tax or
debt dollars per hospitalization that we will be avoiding. Whether this is cost effective I leave
up to your interpretation.

What’s next for Pfizer and Paxlovid?

Pfizer is applying for an emergency use authorization. The full trial is supposed to be
complete by April 2022.

Citations for this Paxlovid Content

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Pfizer press release HERE. https://investors.pfizer.com/investor-news/press-release-
details/2021/Pfizers-Novel-COVID-19-Oral-Antiviral-Treatment-Candidate-Reduced-Risk-of-
Hospitalization-or-Death-by-89-in-Interim-Analysis-of-Phase-23-EPIC-HR-Study/default.aspx

Link to study on ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT04960202

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Paxlovid Reel/Short/TikTok Script

There is a new upcoming therapy for outpatient you-know-what
This info is based a press-release by Pfizer from 11/5
The interim analysis of the EPIC-HR trial showed promising results
This is NOT medical advice
I cannot tackle the details in one minute.
Read the press-release for yourself and do not trust me.
They analyzed over 1200 of the planned 3000 high-risk patients in the trial
If the therapy is started by day 3 of symptoms, it met the primary outcome

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If it’s started by day 5, the effect is still good, but not as good.
the primary outcome was risk of hospitalization or death.
how much did it decrease this risk? By 89%.
What does this mean?
One has to treat 16.1 patients with this therapy to keep someone out of the hospital.
What is the regimen?
It is to be taken twice a day for 5 days.
How much will it cost?
Word on the street is that it will be around $700 per regimen
So over $11,000 per patient kept out of the hospital
Taxpayers will be footing this bill.
Any side effects?
Nothing worse than the effects of having you-know-what
When will this hit the streets?
An emergency use authorization has been applied for and it’s currently in production
What are your thoughts?

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