Thu 2021-Dec-09

FDA Grants EUA to AstraZeneca's Evusheld for COVID-19 Prevention

Tagged: COVID / PharmaAndBiotech

Guess what? Yesterday, the FDA gave Emergency Use Authorization to another COVID-19 medication, Evusheld from AstraZeneca. Yeah… I didn’t know, either!

The FDA EUA’d what, now?

AP: evusheld The FDA granted an Emergency Use Authorization to Evusheld. (Yeah, I also spelled it “-shield” the first few times I tried to type it. Terrible name, but then all drug names are terrible to some degree.)

Now, I’d never heard of this! It’s not like I spend my time browsing ClinicalTrials.gov, but I like to think I have some idea what’s In the Pipeline. So to have this pop up was a pleasant surprise.

I searched the calendars of the FDA AMBAC and VRBPAC committees, and it’s not there. It appears this is one of those instances where the FDA just went and made up its own mind, without convening a panel of outside experts. (Let’s hope for paxlovid? Hmm.) Here are the primary data sources:

AP: FDA approves an antibody PREVENTIVE for COVID-19

  • The Associated Press reported yesterday [1] that the FDA has granted the EUA, and a few details as well as the snazzy box photo above.
    AstraZeneca: Press release announcing FDA EUA's long-lasting abs Evusheld
  • At about the same time, AstraZeneca issued a press release [2], saying more or less the same thing, how proud they were of AZD7442, and how they wish we’d all call it by the new copyrighted name evusheld.
    FDA: Press release announcing EUA for long-lasting monoclonal ab preventative
  • The FDA issued a news release [3] giving lots of details without the corporate-speak, but with the government-speak and medical-speak.
    FDA: Formal letter of Emergency Use Approval for Evusheld
  • Finally, in case you’ve never seen such a thing, there is the FDA’s formal EUA Letter. [4] These are not simple documents, since they have lots of formal legal implications, and instruct the drug maker exactly what they can and cannot do, and what they can and cannot say about their new medication. So it’s 10 pages of dense language.

Ok, what’s it do?

I waded through all that, so you don’t have to. Here are the high points:

  • This is an antibody therapy (actually 2 of them, tixagevimab and cigavimab, given as simultaneous shots).
    • These abs target distinct, nonoverlapping, (relatively conserved?) portions of the SARS-CoV2 spike protein.
    • Doing combination therapy (yay!) like this confers some robustness against mutation. None of the Omicron mutations relevant to evusheld neutralized it. In vitro experiments show evusheld works against Delta and Mu, also.
  • Unlike other antibody therapies, these have been engineered to have a long lifetime in the body, like 6 months, maybe up to 12. (I have no idea how that works, given that until today I didn’t know it was possible. Things move fast, or at least faster than me. And that’s a good thing.)
  • It conveys 6 months or so of immunity, at a level of 77% efficacy. That’s not as good as vaccination, but it’s way better than nothing for people who can’t be vaccinated.
  • It is for people who are so immunocompromised that vaccination is not an option. That means cancer patients, organ transplant recipients, people taking immunosuppressants for RA, and so on.
  • That amounts to perhaps 2% – 3% of the US population; it might be different worldwide. In the US, that’s 6.6 – 9.9 million people.
  • It is not approved for use as a therapeutic for people who already have COVID-19, nor is it approved as a prophylactic for people who have been exposed. It is also not for people who want to avoid vaccination.
  • Specifically: It’s authorized for…
    • Adults & children over 12 who mass at least 40kg (88lb),
    • Who are not currently infected with SARS-CoV2 virus & have not been recently exposed,
    • Whose immune systems haven’t (or probably won’t?) respond to COVID-19 vaccination (as detailed in the fact sheet [5]), or have a history of severe allergic reactions to the COVID-19 vaccinations,
  • The cost is quite different from vaccination:
    • evusheld is around $1000/dose,
    • compared to about $30/dose for vaccination.
  • The trial (PROVENT [6]) had 3441 subjects getting evusheld and 1731 getting a placebo.
    • I was unable to find the infection rates to confirm the efficacy of 77% or get confidence limits; apparently the results haven’t beeen posted to ClinicalTrials.gov yet?!
    • And since it appears not to have gone before one of the committees, I can’t find their submission docs either. It goes faster, but less transparently.
  • There were some rare, but serious cardiac events slightly more frequently in the treatment arm. Absent the actual counts of data, I can’t confirm or deny statistical significance.
  • The US government has bought 700,000 doses, which it will distribute to the states gratis and pro rata.
  • The FDA’s formal letter granting EUA is about as long and complicated as you’d expect.

The Weekend Conclusion

It’s probably not relevant to you personally, since it applies only to 2% – 3% of the population. On the other hand, it is relevant to you personally: we all owe each other a moral duty of mutual care, and our immunocompromised brothers and sisters need this. It’s relevant to all of us to help them out.

So… at least we’re doing that.


Notes & References

1: M Perrone, “New COVID-19 antibody drug OK’d to protect most vulnerable”, Associated Press, 2021-Dec-08.

2: AstraZeneca Staff, “Evusheld (formerly AZD7442) long-acting antibody combination authorised for emergency use in the US for pre-exposure prophylaxis (prevention) of COVID-19”, AstraZeneca Press Releases, 2021-Dec-08.

3: C Tantibanchachai, “Coronavirus (COVID-19) Update: FDA Authorizes New Long-Acting Monoclonal Antibodies for Pre-exposure Prevention of COVID-19 in Certain Individuals”, FDA News Releases, 2021-Dec-08.

4: JA O’Shaughnessy (Acting Chief Scientist, FDA), “Emergency Use Authorization 104”, FDA EUA Letters, 2021-Dec-08.

5: FDA Staff, “FACT SHEET FOR HEALTHCARE PROVIDERS: EMERGENCY USE AUTHORIZATION FOR EVUSHELD™ (tixagevimab co-packaged with cilgavimab)”, FDA Fact Sheets, retrieved 2021-Dec-09.

6: AstraZeneca Staff, “Phase III Double-blind, Placebo-controlled Study of AZD7442 for Pre-exposure Prophylaxis of COVID-19 in Adult. (PROVENT)”, ClinicalTrials.gov, retrieved 2021-Dec-09.

Written Thu 2021-Dec-09

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