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AstraZeneca Gets the Bad News

After writing about Merck’s successes (so far) in immuno-oncology, it’s time to write about AstraZeneca’s failure. When the rumors started flying about Pascal Soriot leaving the company, one of the speculations was that the MYSTIC trial of the company’s PD-L1 (Imfinzi, durvalumab) and CTLA4 (trememelimab) therapies might be in trouble. Soriot ended up staying (so far), but there was indeed something to those premonitions. (To be sure, he had not exactly damped things down by giving an interview to the Financial Times about the gloomy forecast for AZ should the trial not come through as hoped).
The company is releasing earnings today, and last night people were wondering if this would be the occasion for an announcement about MYSTIC. Sadly, that’s just what happened: the combination missed its primary clinical endpoint (progression-free survival), and as I write, that news has wiped twelve billion dollars off the company’s market capitalization. You don’t often see a company the size of AstraZeneca showing a 15% move in their stock in one day, but here it is. The fallout has coated Bristol-Myers Squibb, who are of course also working in this area, and at the moment, they’re down about 6% premarket just on sheer jitters. Merck, meanwhile, is up by nearly the same amount, and neither of those are small moves on this scale, either.
AZ says that they’re waiting for further data next year on overall survival, but if you’ve wiped out on progression-free survival (considered, with good reason, to be an easier endpoint), then the odds for recovery in overall survival itself are long. It’s true that this is the endpoint that really matters, and you can’t declare the trial a total failure until those numbers are in, but the prospects are not good.
The company has signed a very large deal with Merck to develop their PARP and MEK compounds, because Merck is interested in them both for themselves and as combinations with Keytruda. But you’d have to think that can’t make up for Imfinzi coming up short (investors certainly don’t think it, from what’s happening). In the previous post, I talked about the effect of luck on drug discovery, and on this area of it in particular, and here you have another exhibit. Immuno-oncology is a tremendously exciting field. But we don’t truly understand it, and won’t for some time, and that means that things like this are going to happen. It’ll happen again, too, to someone. Strap in.

7 comments on “AstraZeneca Gets the Bad News”

  1. Neo says:

    “Immuno-oncology is a tremendously exciting field. But we don’t truly understand it.” Interesting comment: which drug discovery area we truly understand according to you?

    1. a. nonymaus says:

      It is almost tautological that we fully understand no drug discovery areas. Once we truly understand an area, we have already applied this knowledge and no more discoveries are possible.

      1. Chris Phoenix says:

        To an engineer, a fully understood area is ripe for invention.

  2. steve says:

    It looks more and more like PD-L1 is just the wrong target and you need to block PD-1 instead.

    1. Anon2 says:

      Blocking PD-1 gives another bunch of unwanted side-effects. That’s been shown already as well. The data seemed to suggest that PD-L1 is such a great target, because it does not effect the desired PD-L2 / PD-1 interaction

      1. steve says:

        Interesting theory but PD-1 has proven much more effective in the clinic.

      2. Immuno-oncologist says:

        Actually the toxicities are basically the same between anti-PD1 and anti-PDL1.

        Anti-PD-1 may work better because PD1+ T cells transit through the blood, whereas PD-L1 is on the tumor where antibodies have poor penetration.

        In any case, this is a surprising and disappointing result.

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