@DocMcstuffinsGet some OtherPerspective :
Clinically, patients who fail to respond to steroids and additional immunosuppressive agents are at increased risk for morbidity associated with infections and uncontrolled aGVHD, as well as an increased risk of mortality. The poor prognosis of severe aGVHD is well documented, with long-term survival probabilities of 20% for grade III and <5% for grade IV .Thus, steroid-refractory aGVHD represents a significant clinical challenge. J Kurtzberg
Dear Doc, do some more research. If after studying the results from GVHD001 and the Expanded Access Programme totalling over 290 patients in an ultra orphan disease you cannot see the efficacy and safety profile in such severely ill patients , you are a lost cause. In my opinion, the four year mortality stats linked to the most accurate ST2 biomarkers, make approval a certainty ! Remember, enrolment at baseline for GVHD001 had 88% of patients with Grade C/D. In my opinion, to ignore its own ODAC panel in these circumstances , the FDA would be totally negligent. Look at the statistics below and try to comprehend the incredible efficacy shown by Remestemcel-L
Lets review some other data , to put things in perspective .
The Reach 2 trials which were used as the basis for approval for Ruxolitinib (see also Reach 1) for the indication of sr aGVHD and are well worth a read in the NEJM (see second link below )
Perhaps one of the most startling revelations was the duration of response against Best Available Therapy. If you go to the supplementary appendices. ECP was the most frequently called upon alternative therapy. The graph below shows different data (astctjournal) from a larger more detailed peer review into the efficacy of ECP.
The illustration clearly demonstrates the shocking long term survival rates for ECP when shown as responders and non responders. To put onto greater context the reviewer noted a trend towards better survival in patients with Grade II aGVHD compared to those with Grade III disease (median 20 months versus 6 months P=.07). Only 6 months !!!
Now consider this ECP is currently used as second line therapy of choice by many practitioners despite the fact that most of the studies published on the effectiveness are retrospective single centre studies for adults and pediatric patients and despite the fact that evidence of its efficacy, remains largely elusive…..you don’t say !
https://www.astctjournal.org/article/S1083-8791%2820%2930001-X/fulltext#seccesectitle0005
https://www.nejm.org/doi/full/10.1056/NEJMoa1917635Now, once someone is diagnosed with acute steroid refractory GVHD there is currently only one treatment FDA authorised option, namely Ruxolitinib ….but here comes the interesting part….according to Florent Malard , in the extremely important category of Gastro Intestinal disease, 40% of patients fail to respond to Ruxolitinib ! The author states there is a pressing unmet need for alternative treatments. Are you listening FDA !
https://gvhdhub.com/medical-information/the-results-of-the-expanded-access-program-using-maat013-for-steroid-refractory-gi-gvhdEven the principal investigator for the Reach trials Robert Zeiser acknowledges the seriousness of the problem in a March 23 article. He states “amongst people with Grade II-IV aGVHD approx 70% have some form of GI involvement….historically the rate of overall survival over two years after the onset of either stage 3 or stage 4 GI GVHD is approximately 25%….with 73% of patients developing resistance to steroid therapy after only 2 weeks from the onset of Grade III/IV GI GVHD.”
https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.18778Listen people this is no joke. The figures may be twisted and buried in 300 pages appendices ..but Ruxolitinib clearly has questionable efficacy when measured in terms of long term durability…especially in Grade C/D. Looking at the number of patients discontinuing therapy in severe grades, I have found cases where the Ruxolitinib refractory populations have better overall survival statistics. When one considers, that ECP is for many practitioners the next alternative therapy for severe grades I want to scream…no I want to RAGE, at the incompetence of certain individuals. The antics of the shorters should have no place in determining the survival of a child with this horrendous disease…some of the people posting here are beneath contempt . OP
Please do not rely on the accuracy of any facts , links or opinions expressed in the above post when making an investment decision . The only opinion that matters right now is that of the FDA in determining short term success or failure for this Company. I strongly believe that Ryoncil will be approved now that additional data has been forthcoming which deals with the requirements of the CRL.
(20min delay)