Cell Therapy News/Articles, page-319

Crohn's Disease 

I found this update from 2014:

http://www.orphan-drugs.org/2014/04/29/mesoblast-provides-update-clinical-programs-prochymal-crohns-disease-acute-graft-versus-host-disease/

"Two interim analyses have been performed in this trial to date, including a pre-determined futility analysis which resulted in temporary cessation of recruitment. The trial remained blinded to permit an interim analysis of all 207 patients enrolled in the study to that stage, of which 148 patients had completed the 28 day primary endpoint assessment. The results showed that the effect size, or difference between the Prochymal® and placebo response rates, of one of the two active dose arms of Prochymal® was consistent with the original statistical assumptions of the protocol and was significantly outperforming placebo."

Seems to me the bar in our CD trail was high. Primary endpoint is remission at day 28.  Patients in all arms had high CDAI exceeding 350. 80% had undergone prior surgery. 

Takeda's Vedolizumab was approved and has been widely adopted although it failed to get anyone in remission after six weeks. Gemini 2 induction trial of 360 patients showed no difference in CDA-100 versus placebo.  

Kotze et al (2018) review trials of Ustekinumab, which has been approved for CD. Primary end point was clinical response. In one trial there was a high placebo response.  Authors say: "Previous anti-TNF failure is associated with nominally lower response rates in the UNITI trial program and has been associated with poorer response in open-label studies." 

Ma et al's (2017) study in Ustekinumab using stricter guidelines for remission found it was only achieved in 31/111 patients. So UST will potentially be more effective in milder disease.  You wouldn't use it, however, for those cases in clinical practice. You'd use  Infliximab first line, then if that didn't work, Humira.  So where was UST's  place supposed to be anyway? Kotze et al say that positioning UST as second-line after anti-TNF failure is 'debatable'.

MSB's IV CD could be important  considering the following:

Our cells are immunomodulatory and don't suppress the immune system too broadly. This is the way medicine is trying to move with more targeted therapy (what VDZ was supposed to be).  It's particularly important imo in the light of what Paul Moayeddi says IBD is now thought to be. 

The worst cases respond the best to our cells.  If I recall right, SI said RA patients who had failed multiple biologics had the best response.

Our product would have a clear position in the market; the newer drugs are not up to the job of the biologic refractory group.

 Patients who are refractory often have severe disease. CD and GI-GvHD have similar features and GvHD is 'the mother of all inflammation'.


The silence from Media Analysts is imo strange considering the following:

MSCs being immunomodulatary, their application in atuoimmune diseases is most likely. Anyone can see the number of clinical trials in MSCs in autoimmune Diseases.

GI-GvHD and CD similarity is obvious to anyone reasonably intelligent. For years 'Prochymal' has been on website for both.

Our p3 CD completed last year. A candidate for CD is the first MSC product approved outside Japan. Our IV CD candidate, however, is still not mentioned, although diabetes and RA are. 

CD is a fast growing blockbuster market. Anyone can see what Vedolizumab/ Entyvio has earned for Takeda

I find the silence from media analysts on CD strange as to be disingenuous. GvHD results tell me MSB's cells have potential application in any autoimmune disease. Treat the microbiome at the same time.  For their big money candidates, however, MSB has chosen to concentrate on  CBP and CHF, which I've worried about a fair bit as they seems such difficult conditions. 

The research I've done on MSCs and CBP make me reasonably optimistic they work, also our p2 results. I'm hopeful for partnership in this because for the mass market, it looks to me like it's our candidate or nothing.

ALL IMO. GLTAH