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Clinical Trials

A Quiet And Sudden Exit for Amiselimod

Here’s an example of a common behavior in this industry – and to be fair, in many others as well. Big deals are celebrated and press-released at the outset, but if things don’t work out, they end very quietly – as quietly as possible. Sometimes that’s not very possible at all, because a big Phase III failure (for example) is pretty hard to play down. But when something derails earlier in the process, companies generally try to move past that news as quickly as possible.

That’s what Biogen looks to be doing with amiselimod, a ligand for the sphingosine 1-phosphate receptor that they picked up from Mitsubishi/Tanabe just a year ago. Results of a Phase II trial in multiple sclerosis were, in fact, published in late August, and it looked pretty good at preventing new lesions when assessed by imaging techniques, with nothing flagged for safety. Celgene has a drug candidate (ozanimod, acquired from Receptos) targeting the same receptor, and that one is moving along as far as anyone knows.

But amiselimod was moving along fine, as far as anyone knew, until yesterday. In Biogen’s earnings report, a brief note mentioned that development of the compound had been discontinued, with no explanation at all. Something caused this program to hit the skids most thoroughly, but what? I’m sure that people will be questioning Biogen for more details, which I hope are forthcoming, but the two things that I can think of are both tox-related. They might have seen further data from the human trials that showed something unexpected, although I think that’s unlikely, or they might have seen something bad in a long-term animal study. I recall some PPAR alpha-gamma compounds abruptly dropping out of the clinic some years ago because of this sort of thing (two-year rodent tox).

The folks at Celgene will be very interested to hear anything they can, you can count on that. If this was a tox signal (and I think that’s the likely problem), then the first question is always “mechanism-related or compound-related?” Not always an easy question to answer, that, but it’ll be crucial.

18 comments on “A Quiet And Sudden Exit for Amiselimod”

  1. steve says:

    Hard to see how it’s a class effect when fingolimod is an approved drug. Amiselimod is a second-gen fingolimod which was supposed to reduce the brachycardia side effects. It might have had tox but I wouldn’t think it would kill the whole class of compounds given that fingolimod is already on the market.

    1. bhip says:

      It could well be a structure-related (i.e. off target) toxicology finding or, just as likely, a commercial decision i.e. too late to the party, no apparent advantage over fingolimod or the Novartis follow-up, BAF312,

      1. John Wayne says:

        It is very tough to come up with a compound that is competitive with therapy that will go generic before you get through your clinical evaluation. This is bad news, more choices for patients would have been a good thing.

  2. Isidore says:

    It’s analogous to companies sending out email notices when a new employee joins the company, especially someone with a good reputation, but being silent when someone departs, never mind if one is fired.

    1. RB says:

      Perhaps they just realized that they would be launching into a generic market with an undifferentiated compound.

  3. JSR says:

    And GSK quietly killed their p38 inhibitor. Finally, you might say. But why exactly was it killed?

    1. Schnatterer says:

      You mean losmapimod which was in a big cardiovascular study?
      Where did you get the information?

  4. Mol Biologist says:

    IMO just as in case with catK inhibitors you are playing with fire.
    One of the possible complication may be non-alcoholic fatty liver disease (NAFLD) and ultimately cirrhosis would make clinical manifestation of IBD is even worse.

  5. asdf says:

    I would have thought amiselimod was covered by existing patents??

  6. Mike Ehlers, Biogen R&D chief, said in the recent earnings call that the decision to axe amiselimod had to do with the regulatory and competitive landscape. I’m thinking Ozanimod and ocrelizumab made them think twice.

  7. loupgarous says:

    Lack of differentiation/smallish market, by comparison with recombinant insulin-derived compounds, for which there doesn’t seem to be much differentiation in tox or efficacy but a huge and growing market as type II diabetes nonresponsive to oral therapy (and possibly with patients noncompliant with the diet prescribed them) increases in the industrialized world.

    Face it. the Western diet – high in sugar and other highly bioavailable carbohydrates – would fail tox if it were tested as new drugs are. Increased incidence of non-alcoholic fatty liver disease (NAFLD) and type II diabetes would be the major tox signals.

    1. loupgarous says:

      Take it back. The toxicity of the Western diet has latency that wouldn’t show up as a toxicity on the time frame of pre-marketing drug studies. It has, however, been widely and justly criticized for failing tox on an extended “pharmacovigilance” scale.

  8. anonao says:

    Yes, commercial reason is high possibility not to go further and waste money.

    1. Lars says:

      But that does raise the question, what were they expecting with such a close analogue?

      1. Milkshake says:

        maybe the potency was better, or maybe the animal therapeutic index was little wider, which made them hopeful that human efficacy will be better too. Pharma projects have inertia – especially if the top management already proclaimed in front of the investors how exciting their program is, and how they will dominate the market…

        1. anonao says:

          Agree, and it is difficult to kill a project for a compound that actually works (“would be a waste of money to stop now”). And before phase II they may have thought that the compound still had a good future. But if results were not so much better than competitors once phase II ended, well, phase III is a costly step if no return of investment.

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