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Anti-MAP Therapy Support Group

Crohn's MAP Vaccine September 2019 newsletter
Research update
Vaccine Trials Progress:
Phase II Clinical Trial in people with Crohn's disease:

Drumroll… We are excited to report that the Phase II trial in Crohn’s disease has received MHRA approval to proceed!!


We are still awaiting a decision from the Research Ethics Committee (REC) which is the other major mandatory approval required for any trial to begin. We hope that the trial will be able to start around end October/early November 2019.

The trial will be conducted at Guy’s and St Thomas’s Hospitals in 28 patients with:
  • mild Crohn's Disease (with a positive test for MAP)
  • aged between 18-50 years
  • not taking any immunosuppressant medications or biologics
  • resident in the UK and receiving their usual Crohn’s disease care at Guy’s and St Thomas’s trust
Please note that these are not the full eligibility criteria; these will be published online when the trial opens for recruitment. Recruitment has not yet started, so we therefore ask our supporters not to contact us or St Thomas’ Hospital about this.

The trial design will be similar to the Phase 1 Clinical Trials in Oxford and will concentrate again, as required, on Safety and Immunogenicity. We will be using our new MAP test to assess MAP levels before and after vaccination. Further updates will be posted online, so please check the website regularly as there won't be another newsletter before Christmas.

Dr Gaurav Agrawal is a consultant gastroenterologist working with the team at St Thomas’s. Like us, he is feeling very positive about the trial:

"I have been collaborating with Professor Hermon-Taylor for a number of years now and have always believed the science behind the MAP diagnostic test and the vaccine. I am helping to organise the trial to be run at Guy’s Hospital and to assess the impact and safety of the vaccine in Crohn’s sufferers. I have a fantastic team to work with. For me there are two tragedies surrounding Crohn’s disease. First is the impact on sufferers and that people are severely debilitated by this disease. Secondly, that the science behind it is misunderstood, which means that an effective therapy is being ignored. This project will create a paradigm shift in our understanding of Crohn’s. Not only will we provide evidence of MAP causality, but also the creation of a novel therapy to alleviate this condition and many others. It is so important to me that people all over the world support this project, it couldn’t have been done without you. Your support is not only physical and monetary but more importantly emotional. It gives us independence and persistence to overcome obstacles in order to give a better life for so many people."

Phase 1 Safety Trials in healthy volunteers (people who do not have Crohn's disease):

The Jenner Institute, Oxford have recently reported the preliminary data from the prime/boost element of the Phase 1 trial. We are pleased to report that, in those volunteers who have received both vaccines, the MVA HAV vaccine significantly boosted the T cell immune response to prime vaccination. This is the first time that the effect of the full treatment (ie. both vaccine shots given 8 weeks apart) has been seen in humans. This study has yet to be completed and the data will need to be thoroughly analysed at completion. However, we are very encouraged by the results so far!

Full details of this trial.
MAP test update
The validation work on the MAP test is being prepared for publication and the team will be in a position to submit the paper to an appropriate journal the before the end of 2019.

This is what Neil, our senior research scientist, has to say about our recent progress:
"This year has been a busy one in the lab. We recently submitted a grant to the prestigious Rutherford Appleton Laboratory (RAL) in Harwell, Oxfordshire. The aim of this application was to enable us to make use of the super resolution microscopy facilities at the institute, and by doing so increase our understanding of MAP at a cellular level… and get better pictures of MAP under the microscope for our upcoming paper. I’m very pleased to say that we were successful in our application and I’m looking forward to generating some more important data to support our current research. We have also been working towards perfecting techniques that will enable us to generate further data for our antibody validation. Although a lengthy process, such stringent techniques are essential for these reagents to be accepted in future publications on the MAP Vaccine. With the lab work progressing at a fast pace and with the successful application to undertake some ‘state of the art’ microscopy studies at the RAL, spirits are high! It means a lot to us that there are people out there donating hard earned cash to fund this research, as without your support none of this valuable work would have been possible."

Sadly, the institution-wide grant application (led by our team) to the Wellcome Trust for funding to purchase a super-resolution confocal microscope (like the one we will be using at RAL) for King’s College London was unsuccessful. However, we will be resubmitting the proposal to another major funder… so fingers crossed for second time lucky!

We are also currently running a study comparing MAP test results in 30 patients with Crohn’s disease versus 30 healthy controls. This is important as there are very few studies looking at the proportion of healthy people who carry MAP asymptomatically (in other words as a ‘latent’ infection in the same way that may people worldwide have ‘latent TB). As with the vaccine trial, these volunteers will be chosen from St Thomas's existing patient lists.
Fundraising
Fundraising continues as we head into the phase 2 trial. This funding is needed to keep the lab going so that MAP levels can be tracked during the trial period and so that validation of the long awaited MAP blood test can be completed. There are too many fundraisers to mention here but we are so grateful to each and every one of you who has supported the research. Here are two recent examples of your fundraising events:-


In May, Anna Sykes posted: “My husband's grandad, who is 100 in November, has been having a clear out at home. He's got 2 great grandsons with Crohn's so has donated some items to be sold to raise money for the vaccine. We will let you know how much we raise but the Lladro figurines that were kindly donated by Great-Grandad Sykes have been sold on ebay and have raised an amazing £187 so far. We also received an extra donation from a supporter in Austria whilst raising this money so a huge thank you to her.”


In April, Christine Clifford held a raffle to win a beautiful keepsake Fimo picture created by the talented Natalie Haddock of Handmade Fimo Cake Toppers and
Keepsake Gifts . Winner Alexia Emmerson and her daughters were delighted with their picture. A total of over £200 pounds was raised.


Inspired? If you’d like to start a fundraiser of your own, you can find the instructions here (Please note that the pdf needs updating). The suffix code for the vaccine is now TS11359. This is the tag required to ensure that funds go to the Crohn’s MAP Vaccine test research within King’s College London. Example:
https://www.justgiving.com/fundraising/appointments-ts11359 )

The TS11359 code should also be noted on the back of cheques sent to King’s College London (the old one, MEN 9150, is out of date). We have recently amended the Gift Aid form to include this number too.

It has been a very long journey but we are so close now. With your ongoing support, we WILL get this job done!

Our fundraising total as of 17 th September is £ £781,242. As you can see from Neil’s report, this is being put to very good use!
Useful links
If anyone would like more detail about the fundraising structure of this project, please click here.
For our scientific ‘Core Literature pack’ please click here.
To find out how to become a hero click here.
We know of no other charity like this. We are determined to bring an end to Crohn’s.

Please continue to help us.

Thank you
The Crohn’s MAP Vaccine team
 
RedHill Announces Full Results from MAP US Phase 3 Study and Supportive Top-Line Results from MAP US2 Study with RHB-104 in Crohn’s Disease
11 October, 2019
TEL-AVIV, Israel and RALEIGH, N.C., October 11, 2019 RedHill Biopharma Ltd. (Nasdaq: RDHL) (Tel-Aviv Stock Exchange: RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company primarily focused on the development and commercialization of clinical late-stage, proprietary drugs for the treatment of gastrointestinal diseases, today announced full Week 52 results for all subjects in the previously announced positive Phase 3 randomized, controlled study of RHB-104 in Crohn’s disease (the “MAP US study”) and supportive top-line results from the open-label extension Phase 3 study (the “MAP US2 study”).
The full Week 52 results of blinded treatment in the MAP US Phase 3 study with RHB-104 were consistent with the previously reported positive outcomes of the study. The study continued to meet its primary endpoint of clinical remission (CDAI < 150) at week 26 (36.7% vs. 22.4%, p=0.0048), key secondary endpoints of maintenance of remission at weeks 16 and 52 (25.9% vs. 12.1%, p=0.0016) and, notably, durable clinical remission on all visits, week 16 through 52 (18.7% vs. 8.5%, p=0.0077, RHB-104 vs. placebo, respectively).
In the analysis of the complete safety information for the study, a top-line electrocardiogram (ECG) monitoring report for the MAP US study recently received and shared with FDA, demonstrated evidence of progressive prolongation of the QTcF interval across visits, with the largest placebo-corrected ΔQTcF (∆∆QTcF) of 30.6 ms at Week 52 of treatment with RHB-104. None of these QT abnormalities resulted in adverse cardiac events. Clofazimine, as well as clarithromycin (another active component of RHB-104) are known to be associated with QT prolongation. RedHill continues to analyze the data from the RHB-104 studies, including QT prolongation findings and various pharmacokinetic and pharmacodynamic models and, as previously announced, intends to meet with the FDA again in the coming months to discuss the RHB-104 program, including these data.
The MAP US2 open-label extension Phase 3 study evaluated the safety and efficacy of RHB-104 in subjects from the MAP US study with persistent active Crohn’s disease (Crohn’s Disease Active Index (CDAI) ≥ 150) after 26 weeks of blinded study therapy. A total of 54 subjects entered the open-label extension study and 30 subjects completed 52 weeks of treatment.
Interim top-line results from the MAP US2 study demonstrated 27.8% clinical remission with RHB-104 at week 16 and 22.2% remission at week 521. Of the MAP US2 subjects who were previously randomized to the placebo arm (as an add-on to standard-of-care therapies) in the MAP US study and treated with RHB-104 for the first time in the MAP US2 study, 31.6% achieved remission at week 16 and 26.3% achieved remission at week 52. These results further support the potential clinical benefit of treatment with RHB-104 in Crohn’s disease patients.
RHB-104 was found to be generally safe and well tolerated. The incidence of treatment emergent adverse events, serious adverse events and reported adverse events leading to discontinuation in the MAP US2 study were lower than in the active arm of the MAP US study (77.8% vs. 87.3%, 7.4% vs. 18.7% and 9.3% vs. 21.1%, respectively). Similar trends were observed in MAP US2 subjects who received concomitant anti-TNFs, consistent with the safety of treatment with RHB-104 in combination with anti-TNF agents.
The top-line results and subsequent analyses were provided to RedHill by an independent third party following an independent analysis and remain subject to completion of the independent review and analysis of the underlying data, including all safety, secondary and other outcome measures, and completion of the Clinical Study Report (CSR).
The clinical studies with RHB-104 are registered on www.clincaltrials.gov, a web-based service of the U.S. National Institute of Health, that provides access to information on publicly and privately-supported clinical studies.

About RHB-104:

RHB-104 is a proprietary, orally administered antibiotic combination therapy, with intracellular, antimycobacterial and anti-inflammatory properties. The randomized, double-blind, placebo-controlled, first Phase 3 study with RHB-104 in Crohn’s disease (the MAP US study) successfully met both its primary endpoint and key secondary endpoints and presented the benefit of RHB-104 as an add-on therapy to standard-of-care treatments for Crohn’s disease, including anti-TNF agents. The company also reported supportive top-line results from an open-label extension Phase 3 study (MAP US2) evaluating the safety and efficacy of RHB-104 in subjects with persistent active Crohn’s disease after 26 weeks of blinded study therapy in MAP US. RHB-104 was developed based on the hypothesis that Crohn’s disease is caused by Mycobacterium avium subspecies paratuberculosis (MAP) infection in susceptible patients. The development of RHB-104 is consistent with the growing awareness of the possibility that a bacterially-induced dysregulated immune system may contribute to the pathogenesis of various autoimmune diseases of unknown etiology.

About RedHill Biopharma Ltd.

RedHill Biopharma Ltd. (Nasdaq: RDHL) (Tel-Aviv Stock Exchange: RDHL) is a specialty biopharmaceutical company, primarily focused on the development and commercialization of clinical late-stage, proprietary drugs for the treatment of gastrointestinal diseases. RedHill commercializes and promotes several gastrointestinal products in the U.S.: Donnatal® - a prescription oral adjunctive drug used in the treatment of IBS and acute enterocolitis; EnteraGam® - a medical food intended for the dietary management, under medical supervision, of chronic diarrhea and loose stools and Mytesi® - an anti-diarrheal drug indicated for the symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy. RedHill’s key clinical late-stage development programs include: (i) RHB-105 (Talicia®) for the treatment and eradication of Helicobacter pylori infection with a U.S. NDA submitted and accepted for priority review with a target PDUFA action date of November 2, 2019; (ii) RHB-104, with positive top-line results from a first Phase 3 study for Crohn's disease; (iii) RHB-204, with a planned pivotal Phase 3 study for pulmonary nontuberculous mycobacteria (NTM) infections; (iv) RHB-102 (Bekinda®), with positive results from a Phase 3 study for acute gastroenteritis and gastritis and positive results from a Phase 2 study for IBS-D; (v) Yeliva® (ABC294640), a first-in-class SK2 selective inhibitor, targeting multiple oncology, inflammatory and gastrointestinal indications, with an ongoing Phase 2a study for cholangiocarcinoma; (vi) RHB-106, an encapsulated bowel preparation licensed to Salix Pharmaceuticals, Ltd. and (vii) RHB-107, a Phase 2-stage first-in-class, serine protease inhibitor, targeting cancer and inflammatory gastrointestinal diseases. More information about the Company is available at: www.redhillbio.com.

This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements may be preceded by the words “intends,” “may,” “will,” “plans,” “expects,” “anticipates,” “projects,” “predicts,” “estimates,” “aims,” “believes,” “hopes,” “potential” or similar words. Forward-looking statements are based on certain assumptions and are subject to the Company’s continuing review and quality control analysis of clinical data various known and unknown risks and uncertainties, many of which are beyond the Company’s control, and cannot be predicted or quantified and consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, risks related to the occurrence or timing of the RHB-105 (Talicia®) PDUFA action date, risks related to the commencement or timing of our clinical trials with RHB-104, RHB-204, RHB-102 (Bekinda®) and Yeliva®, risks related to meetings scheduled with the FDA, including with regard to RHB-104 for Crohn’s disease, risks relating to side effects associated with use of our therapeutic products, as well as risks and uncertainties associated with (i) the initiation, timing, progress and results of the Company’s research, manufacturing, preclinical studies, clinical trials, and other therapeutic candidate development efforts, and the timing of the commercial launch of its therapeutic candidates; (ii) the Company’s ability to advance its therapeutic candidates into clinical trials or to successfully complete its preclinical studies or clinical trials or the development of a commercial companion diagnostic for the detection of MAP; (iii) the extent and number of additional studies that the Company may be required to conduct and the Company’s receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings, approvals and feedback; (iv) the manufacturing, clinical development, commercialization, and market acceptance of the Company’s therapeutic candidates; (v) the Company’s ability to successfully commercialize and promote Donnatal®, EnteraGam® and Mytesi®; (vi) the Company’s ability to establish and maintain corporate collaborations; (vii) the Company's ability to acquire products approved for marketing in the U.S. that achieve commercial success and build its own marketing and commercialization capabilities; (viii) the interpretation of the properties and characteristics of the Company’s therapeutic candidates and the results obtained with its therapeutic candidates in research, preclinical studies or clinical trials; (ix) the implementation of the Company’s business model, strategic plans for its business and therapeutic candidates; (x) the scope of protection the Company is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; (xi) parties from whom the Company licenses its intellectual property defaulting in their obligations to the Company; (xii) estimates of the Company’s expenses, future revenues, capital requirements and needs for additional financing; (xiii) the effect of patients suffering adverse experiences using investigative drugs under the Company's Expanded Access Program; (xiv) competition from other companies and technologies within the Company’s industry; and (xv) the hiring and employment commencement date of executive managers. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's filings with the Securities and Exchange Commission (SEC), including the Company's Annual Report on Form 20-F filed with the SEC on February 26, 2019, as amended on May 15, 2019. All forward-looking statements included in this press release are made only as of the date of this press release. The Company assumes no obligation to update any written or oral forward-looking statement, whether as a result of new information, future events or otherwise, unless required by law.
Company contact:
Adi Frish
Senior VP Business Development & Licensing
RedHill Biopharma
+972-54-6543-112
adi@redhillbio.com
IR contact (U.S.):
Timothy McCarthy, CFA, MBA
Managing Director, Relationship Manager
LifeSci Advisors, LLC
+1-212-915-2564
tim@lifesciadvisors.com

1 Results were provided by independent third party prior to database lock and are not final

 
The Crohn’s Vaccine


Timelines are current best estimates and are not set in stone. Delays are commonplace in research due to the unpredictable nature of organising and running trials (last updated 09/10/2019).
Progress
The Crohn’s MAP Vaccine is being developed and commercialized by hav-vaccines.com
It has been manufactured by scientists at the Jenner Institute, Oxford at their Clinical BioManufacturing Facility:
http://www.cbf.ox.ac.uk/cbf-collaboration-with-hav-vaccines-ltd-for-crohn-s-disease-vaccine
Manufacture and Phase I trials have been funded by the company HAV Vaccines Ltd who own the intellectual property rights to the Vaccine.
HAV Vaccines Ltd are seeking further investment to complete funding for Phase IIa trials. Companies or individuals interested in investing should contact Mr Michael Stallibrass (Email: stalli@hav-vaccines.com) for more information.
The Vaccine
Prof. Hermon-Taylor, together with Dr Tim Bull and other members of the team at St George’s University of London and scientists at the Jenner Institute University of Oxford, developed a modern DNA vaccine against MAP. This took 10 years and cost around £850,000, much of it donated by the families of Crohn’s patients, without whom this new vaccine would not exist. The key features of the Vaccine are:
  1. Treatment: Modern vaccines can be used to treat, as well as prevent, established chronic infectious diseases. If the vaccine works as well in humans as it does in cattle then there is every chance that it could CURE, or significantly attenuate, Crohn’s Disease. However, it may take time for inflammation to settle and the gut to heal after vaccination in people with longstanding Crohn’s. The vaccine would not be expected to reverse established scarring, such as strictures, at sites of previous active disease.
  2. Prevention: The vaccine could be given to those at higher risk of developing Crohn’s Disease (e.g. children of those with Crohn’s) to prevent them from ever getting the disease. It could also be given to domestic livestock to prevent MAP getting into the food chain in the first place. Although this would not eradicate exposure completely (MAP still exists within the environment) it could dramatically reduce human exposure.
  3. Mechanism of action: The vaccine is what is called a ‘T-cell’ vaccine. T-cells are a type of white blood cell -an important player in the immune system- in particular, for fighting against organisms that hide INSIDE the body’s cells –like MAP does. Many people are exposed to MAP but most don’t get Crohn’s –Why? Because their T-cells can ‘see’ and destroy MAP. In those who do get Crohn’s, the immune system has a ‘blind spot’ –their T-cells cannot see MAP. The vaccine works by UN-BLINDING the immune system to MAP, reversing the immune dysregulation and programming the body’s own T-cells to seek out and destroy cells containing MAP. For general information, there are two informative videos about T Cells and the immune system below.
  4. Efficacy: In extensive tests in animals (in mice and in cattle), 2 shots of the vaccine spaced 8 weeks apart proved to be a powerful, long-lasting stimulant of immunity against MAP. To read the published data from the trial in mice, click here. To read the published data from the trial in cattle, click here.
  5. Safety: There were no apparant adverse effects from the vaccine in either of the animal trials. Obviously the vaccine still needs to be tested in humans… but because it is highly specific, targeting only MAP and MAP-containing cells, we would predict that the safety profile in humans is likely to be very similar to that in animals.
 
King’s College London Thank-You Brochure

President and Principal of King’s College London, Professor Edward Byrne, thanks everyone who has supported Crohn’s test research. In the booklet you can also read contributions from Professor Hermon-Taylor, Dr Amy Hermon-Taylor, Dr Gaurav Agrawal, Dr Paul Cross, Research Fellow Neil Rayment and fundraiser Christine Clifford.
KCL FSD THANK YOU BROCHURE – CROHNS 2019 – DIGITAL AW

 
Antibiotic Add-On Active in Crohn's Disease
More evidence for a mycobacterial origin
Charles Bankhead,October 31, 2019
SAN ANTONIO -- Treatment with an oral antibiotic combination led to clinically and significantly meaningful improvement in clinical response and remission in patients with active Crohn's disease, a randomized placebo-controlled trial showed.

Patients treated with antibiotics targeting Mycobacterium avium paratuberculosis (MAP) had significantly higher rates of clinical remission and response at 26 weeks. Improvement occurred more often in patients taking concomitant anti-tumor necrosis factor (TNF) or immunosuppressive therapy.

A small subgroup analysis suggested the combination of rifabutin, clarithromycin, and clofazimine led to endoscopic healing, David Y. Graham, MD, of Baylor College of Medicine in Houston, reported here at the American College of Gastroenterology meeting.

"Antimicrobial therapy with RHB-104 demonstrated meaningful improvement in the efficacy and biomarkers of active inflammation and endoscopic recovery in patients with active Crohn's disease," said Graham. "The onset of symptomatic improvement was rapid and was seen by at least week 4. Clinical remission occurred as early as week 16 and was sustained through week 52. There was a trend toward corticosteroid-free remission at week 52."

"These data provide further evidence suggesting a role for Mycobacterium avium paratuberculosis, or a similar organism, in the pathogenesis of Crohn's disease," he added. "Remission data and safety data suggest this potentially may be a use of adjuvant therapy to other medications to enhance the response to medical therapy."

In the discussion that followed the presentation, an audience member inquired about the frequency of bacterial infection in Crohn's disease and the potential role of antibiotic therapy in treatment.

"This is either an additional therapy, or it's the beginning of a paradigm shift," Graham responded. "I see this as we're standing at the same place we were standing with Helicobacter 30 years ago, when the question was, have we found something that if we eradicate, would it change the natural history of the disease and cure it. This is going in that direction, but it certainly hasn't gotten there at this point."

Infectious Link?

In response to a question about the causative role of MAP in Crohn's disease and specificity of the antibiotic combination, Graham pointed out that a "tremendous number of other studies" of antibiotics for inflammatory bowel disease failed to demonstrate a clinically meaningful effect. The study is hypothesis generating, he added, and suggests "this is a potential cause and this is a potential treatment."

The bottom line is whether the treatment had an effect on the disease. "The answer unquestionably was yes. It's very positive data to pursue the hypothesis, but the answer is yet to come."

The association between Crohn's disease and infection with MAP dates back to the 1930s. MAP can be cultured from peripheral blood mononuclear cells of patients with Crohn's disease more often than in healthy controls, said Graham. The observations led to the hypothesis that treatment of Crohn's disease with anti-MAP therapy would support a causative role for MAP in Crohn's.

The hypothesis led to a global multicenter, randomized trial to evaluate the efficacy of RHB-104 in patients with moderately or severely active Crohn's disease. Eligibility criteria included diagnosed disease of the ileum and/or colon at least 6 months prior to randomization; active Crohn's disease confirmed by abnormal endoscopy, abnormal imaging, C-reactive protein level ≥1.0 mg/dL, or fecal calprotectin level ≥162.9 µg/g stool; and a Crohn's Disease Activity Index (CDAI) score of 220-450.

Eligible patients were already being treated with one or more medications for Crohn's disease: 5-ASA, corticosteroids, azathioprine, 6-mercaptopurine, methotrexate, infliximab (Remicade), or adalimumab (Humira).

The trial had a primary endpoint of clinical remission (CDAI <150) at week 26. Key secondary endpoints included clinical response (100-point decrease in CDAI) at week 26, clinical remission at weeks 16 and 52, durable remission, and corticosteroid-free remission.

Key Findings

Data analysis included 331 randomized patients who had a mean age of 39, and men accounted for 57% of the study population. Two thirds of the patients had the ileum as the primary disease site, and the time since diagnosis of Crohn's disease averaged 10.6 years. The mean baseline CDAI score was 296, and laboratory values included mean CRP of 1.36 mg/dL and calprotectin of 668 µg/g of stool. About half the patients were on corticosteroids and immunosuppressives, and a fifth were being treated with TNF inhibitors.

After 26 weeks of treatment, 36.7% of patients in the RHB-104 group had attained clinical remission as compared with 23.0% of the placebo group (P=0.007), and 44.0% versus 30.9% had clinical response (P=0.916). Additionally, 42.2% of the RHB-104 group achieved early remission (week 16) versus 29.1% of the placebo group (P=0.015).

Patients on concomitant anti-TNF therapy tended toward a greater absolute benefit (26-week remission rate of 35.5% vs 18.8%, P=0.08), but a significantly greater proportion of patients not treated with TNF inhibitors met the primary endpoint (37% vs 24.8%, P=0.03). Patients in the RHB-104 arm had significantly greater improvement in the abdominal pain and loose bowel movement components of the CDAI at weeks 16 and 20 and at week 24.

In a subgroup of 35 patients assessed endoscopically at 26 weeks, 35.7% of the RHB-104 group had at least 25% improvement in the Simple Endoscopic Score versus 9.5% for the placebo group (P=0.048), and 50% improvement was seen in 28.6% versus 4.8% of patients (P=0.11).

Significantly more patients in the RHB-104 group attained remission plus at least a 50% decrease in fecal calprotectin or CRP at weeks 16 (25.9% vs 9.7%, P=0.0002), 26 (21.1% vs 9.1%, P=0.003), and 52 (16.9% vs 7.9%, P=0.02). The proportion of patients with a calprotectin level ≥162.9 µg/g, decreased significantly through 52 weeks in the RHB-104 group as compared with the placebo group.

Durable remissions occurred significantly more often with RHB-104, including only visits at weeks 16 and 52 (25.3% vs 12.4%, P=0.003) and all visits from week 16 through week 52 (18.7% vs 8.5%, P=0.008).

In general, the type and frequency of adverse events were similar, Graham reported.

The study was supported by RedHill Biopharma.
Graham and several coinvestigators disclosed relationships with RedHill Biopharma, including employment.


 
If MAP was the sole offending agent, you would expect long term treatment with macrolides to be far more effective. That the treatment would take a long time is expected considering other mycobacterial infections like TB often require months of treatment too.

What isn't normal is that patients relapse on those macrolides. The studies are also not trying to detect MAP, and hide behind the idea that it's hard to culture. It is hard to culture, but if so many people with CD supposedly have MAP, where are all those ziehl-neelsen stains showing how the treatment is able to get rid of MAP.

I think the anti-MAP treatments just lower general bacterial load, resulting in an initial improvement in some patients, that is transient. It will potentially leave some patients worse off in the long term. Giving antibiotics that are completely ineffective against gram negative bacteria, for months, is going to give a fitness advantage to enterobacteriaceae like E coli when patients relapse.
 
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Also, don't forget that macrolides don't just have an antibacterial effect, they also to have a mild anti-inflammatory effect. An initial improvement in some crohn's disease patients with a relapse might be attributed to the anti-inflammatory effect of the antibiotics. Giving the macrolides just for their anti-inflammatory effect would be crazy, they have far too many potential side effects for that.
 
A Message from Professor Hermon-Taylor


...

As with so many things, covid-19 is having a major impact on research. At the point at which the pandemic struck, our Phase II vaccine trial was set up and awaiting the final local authorisations to begin. However, all clinical research not directly related to coronavirus has now been paused. This is because taking part in a trial would put patients at risk of catching covid-19, due to the travel involved as well as the inability to maintain social distancing during appointments. Similarly, all laboratory research not related to coronavirus is also on hold (due to the risk of spreading the virus with staff travelling to and from work) and King’s College London is closed. Hence work on our MAP test is currently paused too. We will be ready to go as soon as social distancing requirements are relaxed and permission is given for non-covid related clinical trials to restart and labs to re-open.
I would like to thank all our wonderful supporters for your continuing support during this very difficult time.

Posted on April 17, 2020 by admin1
 
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Putting Crohn's on the MAP: Five Common Questions on the Contribution of Mycobacterium avium subspecies paratuberculosis to the Pathophysiology of Crohn's Disease
Gaurav Agrawal 1 2, John Aitken 3, Harrison Hamblin 4, Michael Collins 5, Thomas J Borody 4

Abstract
For decades, Mycobacterium avium subspecies paratuberculosis (MAP) has been linked to the pathogenesis of Crohn's disease. Despite many investigations and research efforts, there remains no clear unifying explanation of its pathogenicity to humans. Proponents argue Crohn's disease shares many identical features with a granulomatous infection in ruminants termed Johne's disease and similarities with ileo-cecal tuberculosis. Both are caused by species within the Mycobacterium genus. Sceptics assert that since MAP is found in individuals diagnosed with Crohn's disease as well as in healthy population controls, any association with CD is coincidental. This view is supported by the uncertain response of patients to antimicrobial therapy. This report aims to address the controversial aspects of this proposition with information and knowledge gathered from several disciplines, including microbiology and veterinary medicine. The authors hope that this discussion will stimulate further research aimed at confirming or refuting the contribution of MAP to the pathogenesis of Crohn's disease and ultimately lead to advanced targeted clinical therapies.
Keywords: Antibiotic treatment for Crohn's disease; Crohn's disease; Mycobacteria PCR; Mycobacterium avium paratuberculosis; Tuberculosis treatment.

Agrawal G, Aitken J, Hamblin H, Collins M, Borody TJ. Putting Crohn's on the MAP: Five Common Questions on the Contribution of Mycobacterium avium subspecies paratuberculosis to the Pathophysiology of Crohn's Disease. Dig Dis Sci. 2020 Oct 22:1–11. doi: 10.1007/s10620-020-06653-0. Epub ahead of print. PMID: 33089484; PMCID: PMC7577843.

 
Anti-MAP Triple Therapy Supports Immunomodulatory
Therapeutic Response in Crohn’s Disease through Downregulation of NF-κB Activation in the Absence of MAP Detection
We are delighted to share a new paper from Naser et al, showing that several antibiotics have demonstrated anti-inflammatory effects that are independent of their antibacterial properties. They show that anti-MAP triple antibiotics combination (RHB-104) exhibits anti-inflammatory and immunomodulatory activity alongside its known synergistic bactericidal activity against MAP infection. Very encouraging news! Thanks to Ahmad Qasem for sharing with us this latest piece of the MAP puzzle.
Click here to read the full paper.


Posted on November 19, 2020 by admin1
 
Crohn’s MAP Vaccine booster shot proven safe

At last, the paper we have been waiting for!


ABSTRACT: Heterologous prime-boost strategies are known to substantially increase immune responses in viral vectored vaccines. Here we report on safety and immunogenicity of the poxvirus Modified Vaccinia Ankara (MVA) vectored vaccine expressing four Mycobacterium avium subspecies paratuberculosis antigens as a single dose or as a booster vaccine following a simian adenovirus (ChAdOx2) prime. We demonstrate that a heterologous prime-boost schedule is well tolerated and induced T-cell immune responses.

Full paper from Gilbert et al here.
Posted on March 30, 2021 by admin1

 
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