# RedHill Biopharma granted RHB-104 patent until 2029, planning phase III europe trials



## perfectjelly

Great news, maybe it's just 2-3 years away from commercialization, hopefully.
What do you think?

I can't post links yet, but the news are available in RedHill's website


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## rollinstone

You can actually get rhb104 without doing the trial if you have a doctor willing to prescribe the 3 anti-biotics in the regime


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## perfectjelly

rollinstone said:


> You can actually get rhb104 without doing the trial if you have a doctor willing to prescribe the 3 anti-biotics in the regime


That's a huge problem in my country, that's why i'm looking for clinical trials accepting internationals.


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## xeridea

rollinstone said:


> You can actually get rhb104 without doing the trial if you have a doctor willing to prescribe the 3 anti-biotics in the regime


There's more to the trial than just the triple-abx. They're also testing you for MAP with an advanced, newly developed diagnostic test. Getting the abx from your doctor won't prove you're killing MAP or just clearing some other species. My sense is that even all the MAP researchers concede that not 100% of Crohn's cases are caused by MAP.


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## Crohn2357

rollinstone said:


> You can actually get rhb104 without doing the trial if you have a doctor willing to prescribe the 3 anti-biotics in the regime


You can't get the rhb-104. It is  unique  because of its dosage. Dosages of the cocktail antibiotics being used in rhb-104 are very small.


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## perfectjelly

Crohn2357 said:


> You can't get the rhb-104. It is  unique  because of its dosage. Dosages of the cocktail antibiotics being used in rhb-104 are very small.


I find RHB- 104 dosages extremely weird. Why are the so underdosed? Aren't those dosages sub-therapeutical? Won't it compromise their studies, in the same way it compromised the Selby study?


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## perfectjelly

Seems I was mistaken

you can see here: https://clinicaltrials.gov/ct2/show/NCT01951326
5 RHB-104 capsules administered orally BID

I didn't know BID means "bis in die"(twice a day)
Totaling 950 mg Clarithromycin, 450 mg Rifabutin, and 100 mg Clofazamine.
Those doses are therapeutical, even though this study: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385555/

mentions that:  The editorial which accompanied the article acknowledged that, “subtherapeutic doses of rifabutin (450 mg), clarithromycin (750 mg) and clofazimine (50 mg) per day were used, whereas the optimal dose of rifabutin, clarithromycin and clofazimine for treatment of M avium complex infections is 600 mg/d, 1000-2000 mg/d, and 100 mg/d, respectively”

Maybe it will need some tweaking according to body mass when it is finally released.


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## Lady Organic

what is highly encouraging and full of hopes about this trial is that there are 48 study locations. THis means a lot of Gi doctors believe in this treatment. There is even one nearby where I live in Canada. i shall inquire about it soon.


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## irishgal

Very excited about this study! I think of it as Selby done right. The dosages are very close to what I'm taking. I think the clarithro and clofaz should be OK, and the Rifabutin may be a little low but it may have something to do with avoiding side effects and better absorption. I know Rifabutin has the side effect of uveitis, and I read somewhere that the cool thing about this combo is that the grouping of the antibiotics help absorption rates. I guess Rifabutin and Clofaz are poorly absorbed, but adding the clarithro help that, plus I wonder if there's something else in that combo pill that helps more of it to go in and therefore less is necessary. I was assured that Rifabutin was fine to be taken with food in the combo pill and that it got absorbed properly. 

I've heard that they're screening people for MAP, even though they're required to take all comers since there's no standard test for MAP, though that should change soon. John Aitken's test is the best available in the world, since he can GROW the stuff and look at it under the microscope. If you want a test, contact him through the Otakaro site until he sets up something more official. He's a great guy.

Lady Organic - I thought the same thing! Great that all of those study location docs are getting up to speed on MAP therapy.


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## Crohn2357

lady organic said:


> what is highly encouraging and full of hopes about this trial is that there are 48 study locations. This means a lot of gi doctors believe in this treatment. There is even one nearby where i live in canada. I shall inquire about it soon.


+1.


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## Lady Organic

I have contacted the team of researcher in my region and they will recruit only a few people , 20 if i remember. Full placebo arm unfortunately in the trial. so 50% chance to get the treatment. 
I have asked if they test for MAP and the answer is yes, before, during and at the end of the treatment. The GI in charge specializes in IBD.
this is all quite interesting.


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## SauceySciencey

xeridea said:


> There's more to the trial than just the triple-abx. They're also testing you for MAP with an advanced, newly developed diagnostic test. Getting the abx from your doctor won't prove you're killing MAP or just clearing some other species. My sense is that even all the MAP researchers concede that not 100% of Crohn's cases are caused by MAP.



Hopefully they address this. I'm interested in this theory (irrespective of it's validity I believe antibiotics work in some to induce and maintain remission, which itself isn't evidence - there are multiple hypotheses as to why it would work without it necessarily needing MAP alone), but I'm a bit disappointed with some of the research published, and the lack of clear experimental evidence. One group keeps publishing work on how immunosuppressants have anti-map activity, but the methods by which they test this are improper and not in an in vivo context, or indeed an animal model. That's the main argument against MAP in crohn's - immunosuppression would lead to an increase in symptoms, etc. Which is something that startles me somewhat, it's surprisingly easy to test ; take 20 cows with Johne's disease, take 20 with no Johne's disease. Give 10 of each  group cyclophosphamide and/or prednisolone, and ten get placebo. 

They don't do that, though. Not even in mice (which would be arguably cheaper). These guys did, though.

http://www.ncbi.nlm.nih.gov/pubmed/2097495

and that was in 1990...

Still, I'm hopeful long term antibiotics becomes a viable option for some since there is evidence for it. And at the end of the day, however, RedHill isn't going to care about the MAP theory, so long as greater than 20% of treated people get a clinical response, they have a cash injection until 2029.


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## irishgal

Saucey - I think you hit the nail on the head with your assessment of the need for a diagnostic. This seems to be the greatest weakness in most of the research. Kind of hard to test anything when there's no standard diagnostic! I know there are at least two camps working on this since JMC just gave some more info about JHTs progress in testing their new diagnostic. John Aitken in NZ is also working on this, and can successfully grow the mycobacteria found in Crohn's patients in a week or so - which is huge progress. It's previously proved hard to grow. I am hoping 2016 brings some resolution to this question when these camps publish.

As to RedHill, I have met a few of their study docs and got to know Patrick McLean, the RHB104 Product Manager, quite well. While certainly all companies must be concerned with their shareholders and making a profit, they seemed particularly concerned with the well being of the patients. They seemed to have a genuine desire to alleviate Crohn's suffering as a primary goal. Patrick spoke about how moving the patient stories were and how that convinced him to dedicate his life to bringing this drug to trial. Overall, I found them to be a group with a solid moral compass, which was refreshing in this market. So while they are certainly hoping their drug works for Crohn's patients for many reasons, I think it's unfair to say that they don't care about the MAP theory. Don't want to take an attacking tone, and I certainly tend to lump Crohn's drug companies together as caring only about money as well, but this group seemed guided by something more, so I'd like to give them a chance.


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## JMC

Don't underestimate the significance of this paper:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690169/

"The seminal finding from recent investigations, _however, is the detection of Map in healthy individuals with no clinical signs of disease_. The latter observation indicates all humans are susceptible to infection with Map and lends support to the thesis that Map is zoonotic, _with a latent stage of infection similar to tuberculosis, where infection leads to the development of an immune response that controls but does not eliminate the pathogen. _This clarifies one of the reasons why it has been so difficult to document that Map is zoonotic and associated with the pathogenesis of CD and other diseases. As discussed in the present review, a better understanding of the immune response to Map is needed to determine how infection is usually kept under immune control during the latent stage of infection and elucidate the triggering events that lead to disease progression in the natural host and pathogenesis of CD and immune related diseases in humans.


Filling in the gaps, described above, I believe will become the battle ground to explaining the cause of Crohn's.  The argument over whether or not we are infected with MAP, I think it pretty much over, the proof is overwhelming and the papers to close the case will be there in 2016.


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## perfectjelly

quick update: 

http://ibdnewstoday.com/2016/02/11/...ice-of-allowance-for-patent-covering-rhb-104/


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## xeridea

Maybe it's par for the course. But both Prof. JHT and Redhill have pushed back publishing results. It was supposed to be Q1 but both now H2. Just a blip I'm sure, but worries me nonetheless.


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## rollinstone

Fingers crossed the results are promising, was looking forward to them but I guess we'll all have to wait a little longer


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## JMC

xeridea said:


> Maybe it's par for the course. But both Prof. JHT and Redhill have pushed back publishing results. It was supposed to be Q1 but both now H2. Just a blip I'm sure, but worries me nonetheless.


Unfortunately, research projects always seem to take longer than people hope.  As you probably know, I stay in close contact with Prof JHT and I will let you know if there is anything to be concerned about.


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## lmotsie

RHB 104 Trial Phase 3 update.


Got my blood work back today. Prior to starting RHB-104 my C-Reactive Protein level was way high...4.5. Today, after 4 weeks on the RHB-104, it is 1.34. Still considered high, but greatly reduced. This is GREAT news for me in that 1) inflammation has been a HUGE problem for me, and that 2) My GI Doc (who is also the research doctor in Tucson) was going to take me off the trial and have me go on other meds if my inflammation did not show improvement. YAY!I
I can only attribute this to the meds as my CRP level has remained in the 3 plus range the past 2 years, and I have not made any changes in diet, supplements, herbs, or meds since the start of the the trial. My white cell blood count has also significantly gone down as well.
Like


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## Julia S

When will Redhill publish or share interim results? I also find it worrisome that they´re pushing back on releasing data... :/


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## irishgal

Julia S said:


> When will Redhill publish or share interim results? I also find it worrisome that they´re pushing back on releasing data... :/


Looks like final endpoint is Sept 2017, so maybe then. I'm not worried about it being pushed back. They want full enrollment and they are still blinded to effectiveness, so they didn't push back because it's not working. From their press release about it, which is kind of vague, my guess would be that they're working on the accuracy of the companion diagnostic so they can have accurate before and after MAP test results to accompany the effectiveness data. Just a guess though, it could be anything. Maybe they're tweaking the delivery system or something. They were vague.


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## lmotsie

The original end of the trial was September of 17.  But I was just told by my researchers  that they are extending the trial until September 2019.  The trial report is still to be coming out December of this year when the first of the Phase 3 participants have been on the med for 26 weeks.  My research person told me that 1) the meds will still be given for 1 year, with the hope of remission at 26 weeks.  They want to continue to follow us after we discontinue the RHB-104 to see if and when we come out of remission.  The question seems to be whether RHB-104 is something that will cure Crohns, or if it will only put us in long term remission.  Obviously I would prefer a flat out cure, but will take long term remission.  

So far I feel very positive about the future of this drug.
My research team thinks 3 years before it becomes available to the public if it is approved.


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## Julia S

Thanks for the update Imotsie! I'm looking forward to the interim report in December! Do you know if there are any research teams that take patients from overseas?


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## lmotsie

Julia S said:


> Thanks for the update Imotsie! I'm looking forward to the interim report in December! Do you know if there are any research teams that take patients from overseas?


There are.  Go to Centerwatch.com .  It will give u a list of current and upcoming trials in your area.


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## MarkB

lmotsie said:


> The original end of the trial was September of 17 ..snip...


New press release and journal article are out. I just posted / reposted some links in "List of all Past, Current and Future Treatments for IBD."  Reposting below, for your convenience...

I gleaned this news from the anti-MAP therapy RHB-104 from the 'MAP Vaccine Ready for Human Trials' thread, posted by Scared1. Big news for folks tracking treatments of Crohn's. 


On the contrary - very good news if you tuned into their webcast (I did). By increasing their length of the trial - they are able to show greater efficiency because they have a larger sample size, and they are introducing an early stop process for very success results as an option. The interim results are very good and a new paper was published:

"A single capsule formulation of RHB-104 demonstrates higher anti-microbial growth potency for effective treatment of Crohn’s disease associated with Mycobacterium avium subspecies paratuberculosis"  

Additional notes: 
I added the link to the above paper. See also RedHill Biopharma's Crohn's page and their 6 October 2016 announcement. 

Antimicrobial (anti-MAP) therapy is different from the vaccine, but both developing therapies target MAP (mycobacterium avium paratuburculosis). There is much evidence supporting MAP as a cause of Crohn's, although this remains controversial and is ignored by most gastroenterologists and CCFA. If you are not familiar with this topic, good starting places are Phil Nicholson's Crohn's Controversy video, and the Core Literature packet downloadable from Dr. John Hermon-Taylor's group.


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## MarkB

lmotsie said:


> ...  The question seems to be whether RHB-104 is something that will cure Crohns, or if it will only put us in long term remission.  Obviously I would prefer a flat out cure, but will take long term remission.


Something to consider:  The anti-MAP therapy targets MAP as the causative agent.  MAP is in the environment and in the food supply.  So if one does successfully eradicate MAP, and go into long-term remission (or become "cured") from Crohn's, if one gets re-infected it could start all over again.  

Alternatively, if one goes into remission because the MAP counts go way down on the therapy, but MAP isn't 100% killed off in your body, then it could start to slowly grow again.  

I think anti-MAP drugs hold some promise and there's a lot of literature to support that. But we can't expect them to provide a lifetime of immunity.  The Crohn's MAP vaccine, on the other hand, could prove to be that silver bullet but I don't think it is as far along in trials as RHB-104.

I'm not a doctor, and I don't play one on TV.  Wishing you all health, Crohn's remission, and hopefully a cure one day soon.


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## lmotsie

I agree. My thought has been that if rhb104 is successful is killing off the bacteria, and the MAP vaccine proves effective in preventing it from
 starting to begin with, then we really will have a cure.


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## lmotsie

perfectjelly said:


> I find RHB- 104 dosages extremely weird. Why are the so underdosed? Aren't those dosages sub-therapeutical? Won't it compromise their studies, in the same way it compromised the Selby study?


There was a previous study done by Pfizer (I think) that used higher doses of th 3 anti-biotics.  It was not effective.  Personally, I am glad that they are using small amounts in the HB-104.  If you look at some of the side effects of these 3 drugs, they are frightening.  Permanent brown/black discoloration on the face, eyes, etc??  If you google the images of this particular side effect, you will see.


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## Crohn2357

[url="https://ibdnewstoday.com/2016/12/15/clinical-trial-redhill-biopharma-crohns-disease-therapy-will-continue-as-planned/] Clinical Trial of RedHill’s Potential Crohn’s Disease Therapy Set to Continue as Planned [/url]


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