MSB - a new dawn, page-1916

I appreciate all the comments especially those from @Stellowe,@Roy2U,@Phaedrus, and @stanjupiter

A couple of follow on points... regarding personalities, I'm generally supportive of the changes going on at the FDA. VP's comments on approving meds for orphan indications are encouraging for MSB shareholders because those are the trial/approval paths of least resistance going forward. From Dr. Google: "Mesoblast's allogeneic cell therapy, Revascor (rexlemestrocel-L), has received orphan drug designation from the FDA for use in preventing mucosal bleeding in end-stage heart failure patients with a Left Ventricular Assist Device (LVAD). This designation also applies to the treatment of hypoplastic left heart syndrome in children."

Accelerated approval especially for suffering LVAD patients is long overdue imho. Read about their plight. If first hint of efficacy is the new standard, that occurred years ago.

I like some of RFK jr's ideas, but all the above said, I'm less enthusiastic regarding his characterization that the FDA is "waging a war" on stem cells. I don't think he's talking about ending any "war" on Mesoblast's Mesenchymal Stem Cells, rather the MSC's ("Maybe Stem Cells") mixed up in the kitchen sink at your local clinic. Or your clinic in Antigua which is not under FDA jurisdiction and where he reportedly went for treatment. The FDA currently regulates stem cells like a medication - ie scientific proof of efficacy and safety are required via (costly) clinical trials. That position doesn't sit well with a lot of practitioners/patients. They point out that most cell transfers/transplants from one person to another do NOT require FDA approval. For example, a blood transfusion doesn't require FDA approval. Neither does a kidney transplant. Nor a heart transplant. Nor an allogenic bone marrow transplant... which in a considerable percentage of cases leads to a horrific condition called graft vs host disease. That bone marrow transplant can be done simply with a doctor's order. But cells taken from the bone marrow of a third person to treat the graft vs host disease... that there transplant requires FDA approval. Which as MSB shareholders have learned first hand takes years and let's say a billion US dollars or so. The FDA justifies the regulation of stem cells based on the principles of "minimal manipulation" and "autologous use". Stem cells cross both lines unlike the transplants mentioned above which do not. Those are FDA regulations not necessarily codified in law, ie they are regulations subject to change or relaxation. Over the past 20 years the FDA has indeed shut down a number of neighborhood clinics administering Maybe Stem Cells that are manufactured/expanded in cell culture without regulation. The prohibition extends to a patient's own stem cells... if they're expanded in cell culture they cannot legally be infused back into the patient from whom the parent cells were taken. In general, US courts have upheld the FDA position... and clinics have been shuttered... which has led to a market for the treatment of US patients - including RFK jr.- at Maybe Stem Cell clinics in the Caribbean.

Perhaps the prohibition on a patient getting his or her own daughter cells could be relaxed... personally, I would be opposed to anything beyond that. And not just because I'm an MSB shareholder. Rather, I'm an MSB shareholder because I'm opposed to Disallowed and quackery plied against the desperate vulnerable. I believe stem cell transplants require controlled prospective testing with pre-specified indications/end-points, proper dosing, labeling and GMP manufacturing that should all be under FDA purview. I'd feel the same if someone tried to bio-engineer a kidney to replace a heart. That's not an autologous use transplant - some testing and oversight just might be required.

So, let's see how the impending battle plays out.

To answer Stan's question, yes, SGLT2i's and to a lesser extent vericiguat (Verquvo) and others have changed the baseline playing field for treating CHF patients. The use of the former medications is now widespread. All those K-M control curves in Dr. Perrin's EJHF paper have been shifted south. Will the Revascor curve also shift south? It appears the company negotiated with the FDA - in return for being able to use DREAM-HF data to support filing for an AA in LVAD patients, the company will run a confirmatory trial in class ll/lll patients, essentially a DREAM-HF2. But this time I suspect the primary endpoint will be attainable and control patients will be taking SGLT2i's and perhaps other meds like vericiguat that were not used during DREAM-HF1. I think it's a reasonable trade off. It will be interesting to see if the trial (or a separate trial) is extended to include pEF patients, as was done with the SGLT's.

I suggested posting the enrollment numbers for SGLT2i's as a forecast to the road ahead. Partnership? And to reflect on the road traveled. Anyone still think the FDA is treating Mesoblast unfairly? glta, Left-e