Thread by @cha_myoung

1/ The great hope right now is that the orals from @pfizer and @Merck are the “silver bullet” that will bring an “end” to omicron and the pandemic. These are amazing new Rx’s, but deploying them properly will be way harder than people think. 🧵

2/ We now have another weapon in the toolkit with oral pills that do not have the same burdensome requirements of mAbs. ~90% risk reduction from Pfizer’s Paxlovid in high-risk patients is indeed excellent. pfizer.com/news/press-rel…

3/ The FDA EUA for Paxlovid specifies that the treatment must be administered within 5 days of symptoms. The name of the game here is speed: the longer the treatment start is from symptom onset, the less impact these orals will likely have.

4/ Contrast this with the 10-day clock from symptom onset for REGEN-COV, Regeneron’s mAb

5/ This is probably the single most important chart in the recent Pfizer investor presentation on Paxlovid. For many COVID+ patients today, the window for treatment would fall outside the 5-day window and would be too late.

6/ This is particularly true in the US with a fragmented healthcare system with an array of lab providers for COVID tests (Quest/Labcorp), physicians who can diagnose and treat, and pharmacies to dispense meds (CVS/Walgreens)— many of these services are often not in one place.

7/ Even if we had orals available today, the testing debacle would prevent many people from getting treated. To qualify for the orals, you must have a positive PCR or antigen test result. A 5-day odyssey trying to find a test would mean you most definitely missed your window.

8/ The clock really starts with the first exposure to another infected person, and the incubation period looks like it is even shorter with omicron: 3 days from exposure to symptom onset (versus 5 days for wild type).

cdc.gov/mmwr/volumes/7…

9/ If it isn’t somehow painfully obvious already that we need a mega-ton more antigen tests, the need for rapid testing will be ever-more urgent to properly deploy these oral therapies. We need to shorten the cycle from diagnosis to treatment with a lot more speed.

10/ Here is what the exposure-to-treatment sequence would probably look like today:
Day -3 = Exposure to index case
Day 0 = Symptom onset (omicron)
Day 3-5 = Symptoms worsen, seek care
Day 5-10 = COVID+ test result (hugely variable)
Day 10 = Only eligible for mAb (not oral)

11/ Why would people wait to seek care? Because people aren’t conditioned to seek care immediately when they get a sniffle or cough. Here is registry data where the average time from COVID symptom onset to the patient showing up in the ER was >5 days.

annemergmed.com/article/S0196-…

12/ The ideal sequence looks more like this:
Day -3 = Exposure to index case
Day 0 = Symptom onset (omicron)
Day 0-2 = Serial testing with antigen test
Day 2-3 = COVID+ result -> seek medical care
Day 3-4 = Rx dispensed at pharmacy; treatment started with oral

13/ How will people know to do this? This is where the Apple-Google exposure notifications system could be a valuable tool to modify behavior. Imagine if the EN alert told you that you were exposed but also provided info about free Rx if you are high risk w/symptoms.

14/ “Priming” the person who is exposed could be hugely important to accelerating the testing and treatment cycle by activating the exposed person to seek care when they observe first signs of symptoms.

15/ We will need new models of COVID care to effectively test, diagnose, and treat with these new therapies, including telemedicine providers who can orchestrate home testing and Rx deliveries and omnichannel clinics that are a one-stop shop of testing, providers, and treatments.

16/ At @CarbonHealth, we deployed rapid POC Dx machines in all of our clinics this past fall and were able to see sick patients, get them tested immediately, provide results within 30 minutes, and treat eligible COVID+ patients with mAbs — all in the same visit.

17/ Given sensitivity issues with antigen tests that the FDA & NIH have flagged, the value of rapid POC PCR-based diagnostics will be high for high-risk exposures. An earlier test result from a more sensitive test will accelerate the treatment decision.

fda.gov/medical-device…

18/ Once we have adequate supply of the oral therapies, making best use of them will not be a layup. Let’s not waste the opportunity.