@The YankeeThe following is an extract from Stem Cell Institute magazine dated 9th September 2009, which clearly explains how Osiris managed to make a dog’s breakfast of their own trial design for GVHD. For a treatment known to show efficacy in
patients who were refractory to steroids ...to then initiate a trial
combining their therapy with steroids was a self destructive masterpiece if ever i saw one.
OSIRIS conducted their trial using a relatively high proportion of patients
with low grade skin GVHD when Prochymal (Ryoncil) was known to
work best in liver, gut and multi organ Grade 3/4 steroid refractory patients (the most complex and largest part of the market by treatment cost). As if that was not bad enough they were then reported to have messed up the trial design of the Crohn’s Disease trial. It is noteworthy that Osiris signed a $1.38 billion dollar deal with Genzyme which was discontinued post these “Disappointing” trial results. Oh well, Silviu bought the Osiris IP for “a song” and the rest is ancient history . Silviu successfully choose the appropriate primary endpoints the second time round and the therapy sailed though its Phase 3 trials, not to mention the success of Temcell in treating adult srGVHD in Japan as testament to the efficacy in treating the adult market.
Osiris had only themselves to blame...but i feel sorry for the shareholders...the management let them down badly. I do not think that the FDA covered themselves with glory either.
https://www.biospace.com/article/releases/osiris-therapeutics-inc-leaps-on-1-38-billion-genzyme-corporation-stem-cell-deal-/ “Osiris Clinical Trial Results Challenge FDA ProtocolA number of media sources, including The New York Times, recently reported that Prochymal, the leading adult stem cell product manufactured by Osiris Therapeutics, has "failed" two late-stage clinical trials. The term "failed", however, is the direct result of a technicality in FDA definitions and requirements: namely
, the FDA does not recognize subsets of patients who participate in clinical trials. In actuality, however, Prochymal yielded statistically significant, highly impressive data in the specific subset of patients to whom this novel therapy was targeted.Currently under question are two clinical trials in which Prochymal was tested as a therapy for graft-versus-host disease (GvHD), and also for steroid-refractory GvHD. In the clinical trial for steroid-refractory GvHD, the patients who took Prochymal in combination with steroids were found to have a 45% overall response rate, which was less than the 46% response rate for those patients who took steroids in combination with a placebo.In the other clinical trial, for regular, non-steroid-refractory GvHD, it was found that 35% of all patients who received Prochymal exhibited an improvement in the disease, which, when compared to the 30% of patients who improved in response to a placebo, is not statistically significant.When one looks at specific subsets of patients within the clinical trials, however, the data are quite different. Specifically, for patients with a form of GvHD that targets the liver and gastrointestinal tract, there was, in fact, a statistically significant response rate in which dramatic improvements were observed. However, at this time the U.S. FDA (Food and Drug Administration) does not typically approve therapies that are found to benefit only specific subsets of patients.
The Osiris clinical trial results therefore call into question the FDA rules, which many scientists and physicians believe should be updated and revised in this regard.GvHD is a potentially fatal disease in which immune cells from transplanted bone marrow recognize the recipient’s body as foreign and attack it. Of all the various types and cases of GvHD, it is the liver, the gastrointestinal tract, and the skin which are most commonly affected. Not to recognize a subset of patients who show significant improvement specifically in the liver and the gastrointestinal tract, in direct response to Prochymal, is to ignore a therapy that could have the greatest benefit for the greatest number of people. It is just one more example, of many, of how the FDA’s outdated rules and regulations have no scientific applicability whatsoever any facts to t the new field of regenerative medicine. It is just one more instance that proves the urgent importance of revision and updating of FDA laws.Until such a revision actually happens, however, FDA regulators – and therefore most members of the media – are calling the Prochymal trials a "failure". The critically important subset of patients who showed statistically significant improvement in their livers and gastrointestinal tracts, as a result of receiving Prochymal, might beg to differ, however.In fact, 74% of patients in this particular subset achieved complete remission of the disease – an astonishing improvement. If complete remission in nearly three-fourths of all patients in a particular subset cannot be considered "statisticallly significant", nothing can. The fact that this particular "subset" of patients represents the largest group of patients with this particular disease, is also worthy of serious consideration. Still, however, as a matter of general policy, the FDA refuses to recognize patient subsets – and therefore complete remission of the disease in 74% of patients in this particular group is considered a "failure".
Additionally, in the trial for steroid-refractory GvHD, Prochymal was found to increase the survival rate in children from the usual 20% to 60%. The FDA won’t recognize that data either, and therefore this particular trial is also considered to be a "failure". Parents with children who suffer with this condition, and who could therefore benefit from Prochymal, should not be allowed to have Prochymal, according to the FDA.”
https://www.cellmedicine.com/osiris-patient-subsets/I am very interested to see what labelling guidance is provided by the FDA as part of the ongoing BLA application process for paediatric srGVHD. There is compelling evidence that “Ryoncil” has superior efficacy in certain large sections of the grade 3/4 adult srGVHD market. There still exists a reasonable chance that , whilst a confirmatory trial might be requested, Mesoblast might be allowed to sell to the adult market. Our safety profile is so much better than the gold standard therapy “ Jakafi” (Incyte Pharmaceuticals) ...and i hardly think the FDA expect us to use Remestemcel-L just for paediatric patients of Covid 19 ! Even if I am not being realistic in hoping for a dual adult/paediatric approval , I am very confident that in my opinion, physicians will be happy to prescribe the therapy on an “off label” basis to give the best patient care until formal regulatory steps are taken. Remember, that quite correctly, no analysts have considered the possibility of a joint approval when making their forecasts.
Hope that helps clarify some historical facts, often used against Mesoblast by the less knowledgeable .
Mesoblast has great IP.... The world is about to find out ...just how great !
I will leave you with one last thought...for many years SIlviu has been perfecting his manufacturing IP...he uses proprietary media and processes to harvest the mesenchymal cells, which is way ahead of anything currently used in the industry. His xeno free formulations do not even utilise platelet lysates like most of the competition... because he has found something so much better. I will leave you to read two recent process patents which have been published in the last six months... that further compound our advantage over the competition.
https://patents.justia.com/patent/20200040303https://patents.justia.com/patent/10550369Please do not rely on the accuracy of any facts or opinions expressed in this post when making an investment decision. OP
(20min delay)