No ifs, or buts, the six month peri anal fistula results are simply outstanding . 97% clinical response/85% clinical remission, in what i presume is the phase 2 RCT currently being conducted by the Cleveland Clinic as per the link below. I might also speculate that Amy Lightner is using a slightly stricter remission criteria as she discloses that the fistulas have all but dried up completely. I have to caution that the Clinical Trials Registry does not refer to the fact that Mesoblast’s cells are being used, BUTT , lets remember, Alofisel (Takeda) , uses Adipose (FAT) tissue not the bonemarrow used here …and Alofisel had to pay to license Mesoblast IP. Also, Cleveland Clinic are known to be currently harvesting in their GMP labs, our bone marrow mesenchymal stromal cells for trials in Refractory Ulcerative Colitis and Crohns Colitis..there is no evidence of anyone else’s being used (HINT HINT). I suspect the situation is extremely delicate as Takeda have only got a license from Mesoblast for peri anal fistula ….and forked out a fair packet to acquire Tigenix and are subsequently in the throws of very expensive Phase 3 trials in the USA. Please note that the Phase 2 will only have initially treated 15 out of 20 patients with BM MSCs …the crossover for the control is 6 months . Presumably, as the primary endpoint is reached at 6 months , the patients become unblinded on the crossover event ?
“ADMIRE-CD was a randomized, double-blind, controlled, Phase 3 trial investigating the efficacy and safety of Alofisel for the treatment of complex perianal fistulas in 212 adult patients with non-active/mildly active luminal CD.7 A significantly greater proportion of patients in the Alofisel group, compared to the control group, achieved the primary endpoint of combined remission at a 24week follow-up (51.5% vs 35.6%; a difference of 15.8 percentage points; 97.5% CI 0.5-31.2; P =0.021), and this was maintained over 52 weeks (56.3% vs 38.6%; a difference of 17.7 percentage points; 95% CI 4.2-31.2; P =0.01).13 Alofisel treatment was well-tolerated over 52 weeks, with a similar safety profile in the Alofisel group compared to the control group.13* clinicalremission is defined as closure despite gentle finger compression of all external openings treated with darvadstrocel that were draining at baseline† clinicalresponse is defined as closure despite gentle finger compression of ≥50% of external openings treated with darvadstrocel that were draining at baseline”
The commentary which accompanies the clinical trial registration for NCT045196671 which is the Cleveland Clinics latest trial states :
”Unfortunately, perianal fistulizing Crohn's disease is notoriously difficult to cure with 37% of patients experiencing refractory disease. As a result, patients cycle through numerous immunosuppressive medications that can have significant side effects, and >90% undergo multiple surgical interventions putting them at risk of incontinence.The specific rationale for MSCs in perianal Crohn's fistulas is based upon 1) their anti-inflammatory and immunomodulatory properties; 2) several studies reporting the safety and efficacy of MSCs for the treatment of perianal Crohn's fistula; 3) existence of safe manufacturing methods for isolation and expansion of MSCs.This study will enroll 20participants that have Crohn's disease with medically and surgicallyrefractory perianal fistulizing disease. Participants enrolled will be those that meet particular criteria for participation in the clinical trial.Enrolled participants will be randomized to treatment group with adult allogeneic bonemarrow derived mesenchymal stem cells, versus placebo in a 3:1 fashion. Participants in the treatment group will have a direct injection of MSCs at a dose of 75 million cells. This will be given as a direct injection in and around the fistula tract. Participants will be evaluated for complete healing at three months. If complete healing has been achieved, participants will continue to be followed for one year. If complete healing has not been achieved at three months, participants will be eligible for a second injection of MSCs at the same dose of 75 million cells. Control participants without complete healing from placebo will cross over at the 6month visit to receive an injection of MSCs and again three months after this as above, and will be followed for one year after treatment to a total duration of 18months.”
It appears that bone marrow stromal mesenchymal cells are vastly superior to the results shown by Alofisel in the ADMIRE study. Furthermore, there has been evidence in previous studies, that bone marrow mesenchymal cells have exhibited excellent durability of effect out to 4 years . Durability of effect will have a major bearing on future pricing . Lastly , I should point out that the Cleveland Clinic has used 75m cells (a further 75m may be used if needed at 3 months ) whereas Alofisel is dependent on 120m dosing .
Until there is confirmation that it is indeed Mesoblast bone marrow cells being used, it is difficult to know exactly how the market will react . If one considers, the evidence published at ECCO2022 that endoscopic and histology remission was also achieved in the 4 UC patients who definitely received our BM MSCS within 6 weeks/3 months …….being run in parallel at the Cleveland Clinic …we should be inundated with partners for a Phase 3 trial or certainly deserving of a breakthrough therapy designation in SHORT COURSE (HO HO ) I have been spending the last month looking at the main competitors in refractory Crohns Colitis and Ulcerative Colitis. ON THE BASIS OF THE VERYLIMITED numbers shown in the Investigator Lead, Randomised Controlled Studies involving patient data reported from Phase 1/2 trials for only 27 patients in three very linked indications (6/6UC 6/6 CC & 15/20 PAF) at the Cleveland Clinic , I believe we are witnessing a very real revolution in standard of care. I am sure we will be a few years from the finishing line …but these results are nothing but sensational .
If your not sure, remember to watch again Prof Lightner describing how a 17 old boy went into clinical remission at 6 weeks ! In relation to his peri anal fistula
The FDA has held Mesoblast back mainly because of a f’*k up on the choice of primary endpoints and a potency assay. Thank goodness for Amy Lightner . The link between the gut microbiome and srAGVHD and Crohns and UC is well referenced ….a point reinforced by Fred Grossman in a recent press release .
The faecal calprotectin and CRP biomarkers from these trials should add significant weight to our proof of efficacy.
IMO opinion , the share is completely the wrong price ….but i suspect it will take the fund managers months to work it all out. Let’s not forget , brokers research is virtually non existent on this Company…and the management has gone all secret squirrel club at the moment ….so I make this speculation …..if the shares stay at these levels,post FULL publication of the results of this study (and the Cleveland Clinic confirms use of our cells for all three trials), Takeda would be stupid not to make a bid approach. This is not an ideal situation because some shareholders might be stupid enough to accept!
The XBI Index of small to mid size US quoted biotechs is off 44% in the last 12 months last time i looked….including 6% today !
SIlviu needs to start singing, like Julie Andrew’s atop a Swiss mountain …he is going to need a lot of friends to stay an independent company !! OP
Please do not rely on the facts or opinions expressed in the above post when making an investment decision.
MSB Price at posting:
$1.10 Sentiment: Buy Disclosure: Held
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