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.
This post was addended on 12/24/21 given the press release by Pfizer where an emergency use authorization (EUA) has been granted for Paxlovid by the FDA.
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. For a therapy that works in the inpatient setting, check out baricitinib in THIS POST.
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 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 will be complete by April 2022.
ADDENDUM on 12/24/21 that granted the EUA
A press release, not the full trial results, was provided by Pfizer on 12/22 which updated the outcomes. These are the final results of the EPIC-HR trial. I guess we will have to wait until April, as mentioned previously, for that. A quick reminder that the primary outcomes was a composite of hospitalization and death. 0.7% met this endpoint in the paxlovid group and 6.5% in the control group. This means the NNT to prevent a hospitalization or death is 17.2. This is below the numbers from the interim analysis which was listed above where the NNT was 16.1.
The special sauce here is actually found in the subgroup of patients over the age of 65. The rate of the primary outcome in this subgroup was met in 1.1% of the paxlovid group and 16.3% of the control group. Here, I am actually impressed with a NNT of 6.6. In my opinion, this warrants the EUA and a clear advantage of the utilization of paxlovid over molnupiravir. The relative risk reduction here was 94%.
Citations for this Paxlovid Content
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
Press Release on 12/22/21 HERE.
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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 starts by day 3 of symptoms, it met the primary outcome
- 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?