# Current drug pipeline for IBS-D



## lookingforcure (Mar 27, 2012)

Hey all, I was feeling particularly lousy the last week, and I decided to do what I always do when I'm feeling lousy: research on the internet! So basically I did some fairly extensive research on what drugs are currently available for IBS-D (spoiler alert: not much), followed by some research on what drugs are in line to become available in the next few years (also not much, but with some cause for hope). I thought I'd share some of my research with this forum as a convenient resource. Below I've listed just about every research drug I could find currently being tested for IBS-D, organized by how close it is to being ready to go to market. If I've missed anything or if you find another drug, or have more info on one of the drugs listed below please let me know and I can add it to the list.

*Currently available in Asia, status in US/EU unknown:*
Ramosetron - Lo and behold, there is already an excellent IBS medication on the market...unfortunately, it has not been brought to the US and Europe. Ramosetron works the same way as Lotronex (5ht3 antagonist, which is far and away the most successful IBS treatment found thus far). However unlike Lotronex it has zero risk of severe side effects, it is equally effective in both men and women, and it is a fraction of the price. For whatever reason (I suspect it had to do with the Lotronex boondoggle) this medication was never brought to phase III in the US, despite being found safe and effective. I don't really know how pharmaceutical companies operate, but if we could somehow get this company to bring Ramosetron to the US it would be a huge for us. Given the expected explosion in the IBS market over the next decade, you would think Astellas (the makers of Ramosetron) would realize they have a potential blockbuster drug on their hands and want to get in first with their product. I recently contacted the manufacturer for more info, and received an email back welcoming me to call a company rep. Unfortunately due to being out of country I am unable to do so, but if anyone is seriously interested I can pass the info along.

*Phase III:*
MuDelta (Eluxadoline) - This medication acts somewhat like Imodium or Lomotil, stopping diarrhea through a mu opioid process. It also contains a delta opioid antagonist which supposedly works on pain and offsets the problem of constipation that other anti-diarrheals have. Anecdotally it has shown pretty good results. If all goes well this medication should be available by the second half of 2014.

Ibodutant (female only) - This medication showed fairly good results for pain and abnormal defecation in a recent phase II trial, and should be going into phase III in 2014. Like Lotronex, it showed significantly better results in women, and will likely be geared just toward women. More info here.

*Phase II:*

LX1033 - This medication works by blocking a key chemical needed to make serotonin. So it sort of works like Lotronex, but in a more indirect fashion. Rather than blocking the serotonin itself it stops it from being made. It looks fairly promising so far and recently gained fast-track status from the FDA, and the phase II results should be available by the end of 2013.

Asimadoline - This medication works primarily for pain. It has shown mixed results so far, but it may be able to help some people who have pain as their primary symptom.

Obadiah - This is an interesting one. It works for bile acid diarrhea, which medical science now knows is responsible for at least one in three IBS-D diagnoses (European doctors are way ahead of their American counterparts on this one). It showed very promising results in decreasing the amount of bile acid and associated symptoms, but has yet to be tested in a double blind, placebo controlled fashion, so it could be a while off.

ONO-2952 (female only) - Not much info on this one, but it is being researched by a Japanese company and recently entered Phase II. It seems to work on the central nervous system to effect the abnormal brain-gut connection, especially under stress. So if your symptoms are stress related this may be one to watch. This medication is currently only being tested in women.

AST-120 - This is an "adsorbent" medication that is being tested for multiple disorders, including IBS. It works by sucking up bad things in the gut which can cause symptoms, such as histamine and serotonin. Showed promising results, but the weird IBS placebo effect makes it hard to tell how effective this medication actually is. I wasn't able to ascertain if they are moving it into the next phase or not.

*Phase I:*

Asp-7147 - This is a bombesin bb2 antagonist, which apparently works by blocking certain functions that are involved with motility. There is info about a Phase I study about to begin, but that info is one year old, and I can't find anything more recent unfortunately. So this may be promising, but there isn't much out there yet.

Update: Good news! ASP7147 will be beginning phase II trials soon. See more at: http://clinicaltrials.gov/ct2/show/NCT01896583?term=Asp-7147&rank=1

NeuP11 - This is actually a medication for insomnia which is also being tested for several other conditions, including IBS-D. It could hold some promise, but much to early to say.

*Pre-clinical:*

RQ-00310941 - This is a 5HT2b antagonist. So somewhat similar to Lotronex and Ramosetron (which automatically makes it promising), but working on a slightly different receptor. I contacted a rep, who told me it has shown "excellent" results in lab, is basically ready for Phase I, has no safety concerns, and is just looking for an investor. Reports show they have made it a priority. So...any rich IBSers out there want to invest in a potential blockbuster drug which could both make you both wealthy and healthy?







While this drug seems promising, it is unfortunately in early stages and at least 6-7 years off. But keep an eye on this!

RQ-00202730 - This is another drug from the same company (interesting how much of the good IBS drug research seems to be coming coming from Japan these days). It works as a CB2 agonist. It seems to have taken a back seat to RQ-00310941, their other IBS-D drug mentioned above, as I can find very little updated info on it.

ALB-137391(a) - This is another drug that works on 5HT3 like Lotronex and Ramosetron. However it's effect is much weaker, in an apparent effort to avoid constipation and severe side effects. Nevertheless, it could definitely help mediate symptoms. And its also nice to see companies have not been scared off by Lotronex and are still working on the very promising avenue of research that is 5HT meds. More info here.

*Possibly discontinued/status unknown:*
PBI-1737 - very little out there on this, but it seems to work on inflammation. Since low grade inflammation has been hypothesized as a cause for some IBS, this drug hold promise. But again, I couldn't find much on this.

dextofisopam - This med showed some promise in trials a couple years ago, but the company that was making it went bankrupt and so far as I can tell no one has bought up the rights yet. Here's hoping though...

M0014 - This is a 5ht4 antagonist, and was thought to be particularly effective for post infectious IBS. Unfortunately the company making it was bought out, and I can find nothing confirming that any research has been ongoing since then. Here's hoping though...

AV608 - This is an NK1 antagonist that was being tested a few years back, but I can find no recent info on it. It is possible it was discontinued.

So there you have it. If I've learned anything from this research, its that our health is subject to the whims of major pharmaceutical companies. Any day now some accountant (no doubt with perfectly functioning bowels) could decide the opportunity cost of any one of these drugs is too high, and out the window it goes. So my suggestion to everyone is to make your voice heard! Email the companies working on these meds and let them know you are interested! Sign up for a clinical trial! And, for those who have the means, even consider investing in one of the companies. After all, none of these drugs will ever see the light of day without money, and the more you invest the more they'll listen to you. In short, become proactive in the quest to end IBS.

Again, if anyone has any info on any drugs I may have missed, please let me know. And if anyone is interested in talking to that company rep about ramosetron, I can always pass her info along (so long as you're serious).


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## Kathleen M. (Nov 16, 1999)

I think the pharmaceutical companies really want to tap the vast market that is those with IBS.

I think the problem has been more at the FDA level where there have been people on the panel that think that IBS is very minor inconvenience completely and totally treated with fiber and so any risk of side effects is completely and totally unacceptable.

That the FDA has a history of pulling drugs off the market or severely limiting them so you cannot ever make back the investment it takes to bring a drug to market is a lot more chilling than anything else. If they can sell the drugs like any other drug that kills people that have less than life-threatening illnesses they know they would get a good return on investment.


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## rockingirl (Jan 10, 2008)

Interesting! Thanks for this


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## jmc09 (Oct 5, 2009)

The LX1033 is an interesting one as the most effective IBS D drugs have all been HT3 serotonin receptor medications such as Alosetron,Ramosetron and Cilansetron (showed great efficacy but was pulled through a couple of easily avoided incidents.)


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## lookingforcure (Mar 27, 2012)

Yeah, I think LX1033 has the potential to be a good drug if it does what its supposed to. MuDelta just seems like a refined Imodium, treating the symptoms rather than the root cause...I mean, that said, I'll totally take just treating the symptoms if it means I can get through my day!

Kathleen, I think there may be some indication that that attitude at the FDA is changing, based primarily on how many IBS drugs they are now giving fast track status, but who knows. Maybe all the attention over Lotronex and Zelnorm opened some eyes (or at least made them sick enough of us that they want to rush some good drugs out to make us go away, haha). There is definitely that ignorant crowd out there, the Public Citizen types who just say, "you don't need these drugs! Just eat more fiber and stop whining!" but here's hoping that is starting to change...anyway, the newer drugs show much improved safety profiles anyway, so hopefully we won't be having any more drugs ripped away from us.


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## Trudyg (Aug 16, 2002)

You are so right about these folks who think they have the answer. I do mostly health-food/supplements, but for some things you need consistent, reliable relief. And then we get the bozos who simplistically say take fiber or tak activated charcoal. No one has the answer I want--make me normal!


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## Kathleen M. (Nov 16, 1999)

I think if the drug companies are allowed to sell the drugs for IBS it is highly likely most accountants would think it is a good way to go as it is a very common illness that is generally under treated, so there is a good likely hood that if the regulatory agencies let them sell it that they will get a good return on the R&D investment.

Usually the R&D isn't worth it if there are not enough patients or too many similar drugs already on the market, unless the new drug eliminates a side effect, or has some other thing that makes it different enough to create a niche for it.

Like with antihistamines, the first non-drowsy ones had some severe drug interactions, so when they came up with ones that were also less sleep-inducing than Benedry which is also sold as a sleep aid, but didn't have the same dangerous drug interaction problems they went ahead to get those approved and once they were there they even discontinued the ones with the interaction problems.


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## lookingforcure (Mar 27, 2012)

Kathleen, here's hoping! I do think that once drug companies see the success of Linzess and others IBS is going to become a much hotter focus of study, with companies trying to get in on the growing pie. Unfortunately the top end of the clinical pipeline is looking pretty barren right now, and it will probably be 6+ years before we see the results of that rush to get in on the market. At least that would be my estimate, based on how long it typically takes for a drug to go from pre-clinical to market. Times like this I wish I was a billionaire, I would just personally fund the R&D on every one of those drugs, haha.

Anyway, I found another drug that might be of interest to people. It's called LX1032, and it's from the same company (Lexicon) that brought you LX1033, mentioned above. It basically does the exact same thing as LX1033 (decreases the synthesis of serotonin in the gut) through a different method (seems to be more systemic, although it does not effect brain serotonin and side effects are still minimal). It is being tested for carcinoid syndrome and ulcerative colitis rather than IBS, but here is why it is interesting: 1. It does the exact same thing as LX1033. 2. It is in phase III now, which means it could be on the market before LX1033. It has shown great results in reducing diarrhea, and could be a very effective drug for us!

Check it out:

http://www.lexgen.com/pipeline/telotristat-etiprate.html


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## lookingforcure (Mar 27, 2012)

Updated with new info about ASP7147, which will starting phase II trials soon.


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## PD85 (Aug 19, 2010)

Absolutely great thread, thanks for all this info.


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