Simponi (golimumab) Clinical Development for Ulcerative Colitis and Crohn’s

Posted by Jeff Berk, BOLT International

 

I got ten emails overnight, basically all saying “post more stuff related to the upcoming DDW meeting”.  The second highest request was eight emails.  For 2nd place, you get these pretty purple flowers.

 

 

 

 

And for you 1st placers…

Simponi; golimumab (Centocor / Schering-Plough / Merck)

 

  • Simponi (golimumab) is actively being developed for use in ulcerative colitis.  The formulation, an IV for loading and a sub-q for the remainder of induction and for maintenance, will be more acceptable to 3rd

 

“So that opens up the dilemma for Centocor of what do they do about ultimately switching Remicade patients to Simponi because Simponi’s is subcutaneous, right? You can give it IV for loading and then subcutaneous, but it is basically subcutaneous.  So is that regimen, is the Simponi subcutaneous regimen ever going to compete with the Remicade benchmark? I think it will. First of all, that is the ulcerative colitis market.  They haven’t developed it in Crohn’s disease as of yet and I think it is because their strategy is to really develop Simponi for ulcerative colitis and to develop ustekinumab for Crohn’s disease and then go from there.  And so I think in ulcerative colitis it is almost like a product pipeline.  You are like okay Remicade with Centocor, Simponi’s and Centocor’s, I know what I am getting there, will that sort of lead out into keeping it within the family, the Centocor family.  I do believe that Abbott is going to take a bit hit in the next 18 months.

 

“They are moving now towards Crohn’s disease.  Initially, they didn’t want.  I think the reason why they are moving is because they are seeing the same dangers I see for the infliximab world that the antigenicity of the product and the combination with azathioprine at some point will catch up to them.  I think the idea is to go with Simponi which is a much cleaner molecule after they now know how it works and they have to get out of the side effects concentrations and so on for the RA data to now do a rather swift and precise development in Crohn’s disease”.

 

“So I think golimumab would be on the list as far as a development program obviously more for ulcerative colitis than for Crohn’s disease but I can see it as being a player in Crohn’s disease if a company decides to develop it there.  So if they decide to develop it in Crohn’s disease I think it will be a player.  Certainly I think that it will play a major role in IBD going forward.  Obviously, we need to wait for the trials to be finished”.

 

 

  • There are two key advantages for Simponi over other anti-TNF drugs.  Its once-monthly formulation reduces the number of injections.  It is available either by sub-q or intravenous injection.  The infusion is better suited to reach high drug levels needed for induction (for UC or Crohn’s), and then switching to sub-q would be more convenient for maintenance.  And in comparison to other classes of therapeutics, anti-TNF therapy has proven itself in IBD.

 

“I think the major advantage is going to be the flexibility in its dosing with respect to – if they develop it – it is convenient because it can be given both subcutaneous and intravenously.  I think that in general you would us the advantages of it being able to give it IV for the induction phase in both diseases and then being able to give it subcutaneous for the maintenance phase.  So that flexibility certainly gives it a significant advantage over the other anti-TNFs that are out there right now as well as the fact that it has a prolonged half-life, meaning that dosage should be less than what is out there as well”.

 

 

“That sort of captures sort of the essence of the molecule, why you would put it on formulary because I think you will have the drug for both diseases, flexible dosing, more convenient for the patient given its half life, and in a class that has already proven itself in IBD”.

 

 

 

  • Panelists experience is that Remicade is very effective in ulcerative colitis as well, and some question whether golimumab will be closer to Humira than to Remicade.  Experience with open-label use of golimumab didn’t suggest a tremendous response, but since the Humira data is looking so dicey, there is a good chance that Simponi can look comparatively better when the two sets of trial data are held side by side.

 

“What about anything you are seeing for golimumab in UC? We haven’t given that open label to anybody.  It is obviously available commercially for other indications.  We did not have a very favorable experience within the trial.  Now it was a blinded study but for patients who didn’t have a response they could go into the open label.  Even those who didn’t have a response who then went into open label and got open label we didn’t see tremendous response with.  Okay, interesting. I don’t know what other people’s experience has been at other institutions but I just hadn’t been very impressed”. 

 

 

“Simponi is a subcutaneous drug. So that is of course the difference.  We have very little data out yet on Simponi in terms of IBD.  Obviously, it has been pushed first in ulcerative colitis and we have to wait for the read out of the ulcerative colitis trial.  Retrospectively, this was a smart move because Abbott has failed the ulcerative colitis trial, at least halfway failed, as in rather weak what they produced.  If Simponi comes up with good data then you can talk about this being a stronger drug because your people will take that and measure that up against each other.  I think there is a certain marketing advantage if they really can get a good signal in ulcerative colitis”.

 

 

“I don’t know what their plans are for golimumab.  I don’t know why they wouldn’t just push Remicade for everything for ulcerative colitis and Crohn’s disease because it is a great drug, we all use it and we all know it.  I know it has been slipping in Crohn’s disease in terms of marketshare but it is still a huge drug.  Why compete with yourself with golimumab and with data that is not probably as good.  I don’t know.  Once again, that corporate decision that goes way beyond this focus group”.

 

 

 

  • Centocor is in a waiting phase relative to advancing golimumab into pivotal Crohn’s trials.  The impetus for moving forward with golimumab would be a rapid erosion of infliximab sales by adalimumab and to a lesser degree certolizumab.  Neither of those scenarios look very likely.

 

“And then part on the Crohn’s disease side really depends on I think what happens with adalimumab and to a lesser degree certolizumab and how much it erodes into the infliximab market.  I think if Centocor and J&J see that their Crohn’s disease market is being eroded at a level that they are uncomfortable with or an accelerated level they will think about developing the molecule in Crohn’s disease.  That suggests that they are going to wait. Right now they are in a waiting phase”.

 

 

 

  • Centocor / Merck (seeing as arbitration went in Merck’s favor) will have to address a competitive disadvantage in terms of robustness of data on mucosal healing with golimumab.  For ulcerative colitis, they will get some of the way there by using the Mayo score, which has endoscopic and mucosal healing data. If they go forward in Crohn’s disease, as part of the development package they will have a mucosal healing sub-study within the Ph-IIb/Ph-III program.

 

“I think that depending on what the efficacy signal is in ulcerative colitis, because that is where they are focusing right now, they will have all that data just because as part of the Mayo score you will have endoscopic data and mucosal healing.  If they go forward in Crohn’s disease what I suspect will happen is that as part of the development package they will have a mucosal healing sub-study within the same sort of phase IIb/phase III program and I think you will make inferences with it”.

Categories: Crohn's disease, gastroenterology, inflammatory bowel disease, ulcerative colitis
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