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Clinical Trials, Up and Very Much Down

Lots of news at both ends of the scale today. At the bad end would be Arrowhead Pharma, who have been exploring therapeutic RNA interference. That’s a hard row to hoe, and nothing illustrates that better than their announcement that they’re dropping three clinical programs, pretty much all the advanced research that they have, because of problems with their delivery technology. The vehicle formulation showed fatalities in a late-stage primate toxicology check, which led to an FDA hold on the company’s most advanced study, and now they’ve dropped it and two other programs that use the same vehicle. This is accompanied by the expected cratering of the stock price and announcement of layoffs. Arrowhead has other programs and other vehicles, but a lot of possible good news has evaporated for now.

Similarly, Cerecor has been developing CERC-301 (an NMDA ligand originally from Merck) for depression. Alkermes recently reported some encouraging data in this area, which led to a run-up in Cerecor stock, but that came to an abrupt halt as the company announced that the compound showed no benefit at all in its current Phase II trial. As you can see from that press release, the company tried to make something of the data, but to no avail. Talking about what happened on Day 2 of the treatment is not going to do much good when both doses of the drug miss the primary endpoint – I mean, I suppose I understand why companies feel that they have to say things like this, but there’s really no point. This is after a lower-dose Phase II had already failed a couple of years ago; this was the let’s-go-to-higher-doses attempt. The company stock got halved, and the compound itself is presumably dead unless someone has a really bright idea.

And finally for the bad news department today, I hope, is the news that Eli Lilly is going to “reevaluate staffing decisions” in the wake of their recent Phase III Alzheimer’s failure. As that Endpoints article says, though, the company isn’t really being clear about what that means. Layoffs? Not hiring for positions that are technically open? They do say something about “affected employees will learn more”, though, so that doesn’t sound good. The number of times things like this seem to happen in the last couple of months of the year, just in time to put everyone in a festive holiday mood, is remarkable. I’ve experienced something like that personally, and it does add something to the season that you weren’t looking for.

Fortunately, there actually is some good news out there. Bluebird is presenting clinical data today on their CAR-T program in multiple myeloma, and they have some encouraging data from both the efficacy and the toxicity ends. The field needs some of that after Juno’s recent troubles, but Bluebird is reporting no major adverse reactions and a number of strong responses in patients whose cancer had become resistant to a whole list of alternative therapies.

14 comments on “Clinical Trials, Up and Very Much Down”

  1. Dionysius Rex says:

    Given pharma history, I’d be very worried as a Lilly-Erl Wood employee…… short odds on the UK taking a hit (again).

    1. anon says:

      And what about their AMRI in-sourcing staff at the Erl Wood site?

  2. Hap says:

    And finally for the bad news department today, I hope, is the news that Eli Lilly is going to “reevaluate staffing decisions” in the wake of their recent Phase III Alzheimer’s failure. As that Endpoints article says, though, the company isn’t really being clear about what that means.

    If they’re not being clear what that means, it means that either they don’t know (possible) or they know and it’s news they don’t want to be made clear to anyone else. Neither of those options is very good.

  3. steve says:

    Moving into homeopathy where you don’t need trials and the COGS, like the API, is nonexistent.

    1. Mark Thorson says:

      Not necessarily. That may change. See the first item here:

      http://www.ncahf.org/digest16/16-44.html

  4. LiqC says:

    I’m having difficulties finding what is the Arrowhead’s EX1 delivery vehicle made of. Does anyone here know?

    It’s a huge bummer to be killed by excipients…

    1. steve says:

      May not be excipients, may be a general problem with siRNA given Alnylam’s recent toxicities.

      1. Rene DesCartes-DesHorses says:

        Although siRNA may exhibit some general toxicology issues (see the previous discussion following Alnylam’s unpleasant news), that doesn’t seem to be the issue in this case. The news story indicates there was toxicity in primates following administration of vehicle alone. So the question of the composition of the delivery vehicle “EX1” becomes quite important. I’m hoping somebody has some insight on this.

    2. Druid says:

      It seems to be a “protected” amphiphilic polymeric polyamine, with chemical modification of the amines with maleamides easily hydrolysed in acidic late-stage endosomes. Polyamines are very effective at penetrating cell membranes, and useful for condensing RNA or DNA, and great in vitro but often highly toxic in vivo. It appears that in this case the protection, designed for endosome escape, does not fix the problem. This has been holding up non-viral gene therapy and other ideas for cell penetration for decades.

      1. Rene DesCartes-DesHorses says:

        Thanks very much Druid. And here we are again, with potential advances in non-viral gene therapy getting crunched due to problems identifying safe and effective delivery modalities. This becomes an even greater priority after the impressive proof-of-concept in the Alnylam trials. What kind of knock-down did they get for their target protein AAT? -80% or -90%? It was impressive.

  5. Mark Thorson says:

    “whole list of alternative therapies”? So, that would include Reiki and acupuncture?

  6. Isidore says:

    There’s also this
    http://www.itv.com/news/2016-11-30/man-with-prostate-cancer-cured-with-experimental-testosterone-hormone-therapy/
    although no press release (yet) at the Johns Hopkins website.

    1. Morten G says:

      Here you go Isidore. I think this is the press release.
      https://www.eurekalert.org/pub_releases/2016-11/eeco-hha112916.php

  7. Mol Biologist says:

    BACK to the ROOTS. CAR-T trials reminds me the story of treating the bubble babies:
    http://www.yourgenome.org/stories/treating-the-bubble-babies-gene-therapy-in-use
    1. Positive results engenders success.
    2.Cured but with short term effect.
    3. Precise delivery of “mutual aid” or ready-made protein parts necessary for addressee’s stress adaptation and survival.

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