The problem Doc is that evidence does not support your assertion regarding the essential use of randomised clinical trials in orphan designations for rare diseases. Of course an RCT is highly desirable and the gold standard in trial design..but as the stats above point out, orphan indications raise ethical and practical barriers to their use. Furthermore, the guidance notes issued by the FDA for aGVHD continue to state that “fact” so try not to suggest Silviu is testing the patience of his regulator. He has supplied over 100,000 pages of BLA submission reviewed by one of the foremost experts in Philip Krause who was one of the FDA’s most senior experts. The whole purpose of the ODAC expert advisory panel was to filter the clinical and scientific evidence and probabilities and advise the FDA accordingly. CBER ignored them…hardly surprising when you consider the conflicts of interest. I don't suppose you have read Klinkers or Bauers paper on the subject ?
When the meta data of the last 20 years are examined, your oversimplified regurgitation of so called facts regarding RCTs does not past muster. High mortality, oncology based, orphan diseases have a significant likelihood of being FDA approved using SAT (Single Arm Trials) . As you claim to be a man that likes to see “evidence”…I thought I would provide some. Please note high mortality and validated biomarkers rank rather highly in SATs. You may recall that Mesoblast has linked the results of GVHD001 to not just long term mortality outcomes but also to ST2 which has emerged as the most reliable biomarker for evaluating disease progression and client stratification…with use of the MAGIC algorithm. That is real validated science , not the subjective and relatively unreliable clinical grading systems used previously by the FDA. When you “risk adjust” outcomes for disease severity..the results from GVHD001 are extremely impressive in comparison to the null hypothesis examples given by the FDA at the OTAT meeting. If the FDA had monitored the long term mortality of the patients in those other trials …I would bet that they would have been embarrassed at their own submission paper to ODAC.
If one considers that single arm trials were the basis for approval for both adult acute steroid refractory GVHD and for Chronic GVHD indications, I am inclined to believe Prof Itescu when he said the FDA previously guided he could receive at least accelerated approval based on an authorised trial design for GVHD001. I will go one stage further and state that he was quoted in a meeting in 2015, which i have viewed on the internet where he made that disclosure. You also wanted to see evidence that MSCs work better in children rather than adults. As usual , the answer is extremely complex because of the various mechanisms of action … a bit like asking someone to write a thesis to pacify the incessant demands of an internet stalker. I will shortly be discussing one orphan disease where “cardiac output and systemic perfusion” was found to be superior to control in a RCT using our MSCs in young children over time… I should add that this was the findings from a review from the premier paediatric research institution in the USA…not Doc McStuffins .
Mesoblast believe they have one last major hurdle to overcome the second CRL, regarding the potency assay . They believe they have the data to prove their case. If you don’t believe them ….fine..just don’t fill up the forum with the same comments ad nauseum …please. It mortifies me that the current market capitalisation is a reflection of potential financial distress and does not reflect the near term upside of this amazing biotech . Biotechs, by their nature suffer delays and require further funding..that does not mean they have not made major progress and offer tremendous value. In my opinion, a licence deal or a successful refinance and this will pop . OP
Please do not rely on the facts or opinions contained in the above post when making an investment decision. Mesoblast has an extended balance sheet and may need to raise capital in the near future if other alternatives, such as partnering or securitisation of royalty revenues , do not plug the gap in its finances. DYOR
MSB Price at posting:
37.0¢ Sentiment: Hold Disclosure: Held
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