Peter Marks CBER
"Part of the willingness to use the (accelerated) pathway appears to stem from the fact that last yearCongress granted the agency new "teeth" to require confirmatory trials. "For all accelerated approvals, the new teeth we have is that we are going to want to see confirmatory trials well in progress, with some exceptions, as we grant accelerated approval so that we have a better sense that they are actually going to get done," Marks said.
But the CBER leader was adamant that his agency would work with industry and take a case-by-case approach to each individual product.
"With gene therapy under the Regenerative Medicine Advanced Therapy designation, a confirmatory trial could simply be following the cohort youhaveenrolled in your registration trial," he noted. (he later refers to cell and gene therapies )…..
https://www.medpagetoday.com/special-reports/exclusives/104594
Now, consider how relevant, Mesoblasts four year mortality data, verified from the IBMTR, from the cohort of our original Phase 3 treated patients in GVHD001….fits this new guidance"
A CHANGE IN FDA POLICY ….. JUST READ THE LINK ABOVE
As others have also commented…the FDA appears to have woken up…they cannot expect biotechs in the current economic environment to commit billions to stem cell research whilst getting no return. Whilst Japan, Europe, Canada, New Zealand, Korea, etc, have already given the initial green light to various stem cell therapies many years ago, the FDA has effectively determined it was more important to deny access to live saving treatments for children (Ryoncil) whilst they pontificate how it fits within their own research into cell morphology and mechanism of actions… ignoring their own ODAC Committee of expert practioners. for a tiny orphan population with an unmet need and a mortality risk of up to 90%. It was an insane policy. Under these new proposals, allogenic therapies with excellent safety and efficacy, appear likely to be fast tracked. Dare i speculate that Mesoblast, might conceivably be allowed go head to head, with a confirmatory trial against Jakafi (best available therapy…sic) in severe adult acute srGVHD after approval, based on existing clinical evidence that it is equally effective for both adults and paediatric conditions ? That is something Dr Kurtzberg has been suggesting for years. That a welcome turnaround after 20 years of research ! The FDA must be close to acknowledging the science behind biomarker therapy developed by the MAGIC Consortium rather than its insistence on conducting clinical trials using far less accurate patient grading criteria. In Grade C/D disease I believe Ryoncil will slaughter Jakafi, as arguably it achieves no real durable response in Grades C/D other than a few extra months over best available treatments. Ryoncil looks to be twice as efficacious in severe patients, as the durabilty of response and OS data confirms. Anyone believing that our therapy is less effective in adult GVHD has simply missed the point. Before 2008, all clinical data was based on subpotentbatches of Remestemcel...this was a point which possibly festered with the FDA researchers and ultimately may in part have contributed to the original CRL…Mesoblast only disclosed some of the clinical data supporting the manufacturing potency enhancements, late in the BLA application process. As evidenced in other clinical trials for other conditions conducted post 2008 , MSC work in adults ….when given at the correct potency, to those with even slightly elevated CRP levels.
A NEW TREATMENT PARADIGM FOR GVHD GUIDED BY FAR MORE ACCURATE BIOMARKER THERAPY
ST2 has been lauded as the most accurate biomarkers for refractory acute GVHD …especially for severe grade disease where many patients symptoms have to diagnosed subjectively under other clinical grading systems . ST2 can stratify patients with severe disease as early as 7 days, unlike many of the panel biomarkers previously used …therefore i believe that this level of disease biomarker stratification, will allow targeted Ryoncil treatments for refractory Grade D aGVHD for ALL patients ,regardless of age , Ryoncil may shortly dominate treatment protocols as a first line therapy in all age groups….Insurers currently have to fork out between US $1-2m in hospitalisation costs to treat a severe grade paediatric patient …with mortality of up to 90% in severe disease. Would it not make more sense to use Ryoncil as a prophylaxis saving the best part of a million dollars and saving a poor soul ?
Mesoblast has of course applied for full approval for paediatric sr aGVHD, not accelerated approval . Assuming their potency assays are now validated and they navigate pass their PAI , label extension into adult might be a lot quicker than we thought. OP
BLA RESUBMISSION TIMETABLES
A resubmission judged on the precise requirements of a CRL is not the same as an initial BLA application. Many of us have looked up the relevant SOPP’s and are trying to piece together when there might be a “mid cycle” or “late cycle” meeting. However, do resubmissions in these circumstances follow exactly the same format ? In the absence of an ODAC meeting needing to be convened , provided the issues in the CRL have been addressed to the FDA’s satisfaction and labelling and post marketing studies agreed, a decision could come up to several weeks before the long stop PDUFA date of August 2nd 2023 For those connoisseurs of FDA approval history, it is worth pointing out that a treatment for chronic sr GVHD was recently approved six weeks ahead of its PDUFA date !
Please do not rely on the facts or opinions expressed in the above post when making an investment decision.
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