Some extracts from Silviu's letter in the Annual Report.
"We are particularly pleased to see the peer reviewed recognition of our rexlemestrocel-L Phase 2 chronic heart failure (CHF) trial results which will be showcased in a late-breaking session at the American heart Association's (AHA) Scientific Sessions, regarded as the world's most prestigious cardiovascular meeting. The featured sessions is titled 'Building on the Foundations of Treatment: Advances in Heart Failure Therapy.'
Separately, the Mesoblast team will present these clinical results to the FDA in order to receive guidance on the pathway to potential approval for rexlemestrocel-L in the treatment of CHF."
Seems they haven't met with the FDA yet for CHF... "Dr Emerson Perin, Medical Director of Texas Heart Institute, and Clinical Professor, Baylor College of Medicine, will give the late breaking presentation at the upcoming AHA annual meeting, titled 'Randomized Trial of Targeted Transendocardial Delivery of Mesenchymal Precursor Cells in High-Risk Chronic Heart Failure Patients with Reduced Ejection Fraction'. Late-Breaking Science sessions are innovative and provide the latest breakthroughs in clinical science.
These sessions provide notable exposure and recognition for studies likely to have a significant impact on clinical practice and/or to make significant advances in a scientific field." I can't wait to see Dr Perin's presentation... "we were looking for silver, and we hit diamonds"... come on Emerson... drop that one in the presentation for us!"There is a significant unmet need for a safe, efficacious, and durable
opioid-sparing treatment in patients with chronic low back pain (CLBP) due to severely inflamed degenerative disc disease. In view of the findings from our recent Phase 3 trial in CLBP patients that a single injection of rexlemestrocel-L + hyaluronic acid carrier may provide a safe, durable, and effective
opioid-sparing therapy, and that the greatest benefits are seen when administered earlier in the disease process before irreversible fibrosis of the intervertebral disc has occurred,
Mesoblast will receive feedback shortly from the FDA on the pathway to US regulatory approval in these patients." I am pretty sure Mesoblast may have met with the FDA in Q3, as they advised that in early July they had requested a Type C meeting with the FDA, which would have been held in Q3 i.e. Jul/Aug/Sep. If it was a bad outcome, we would have heard about it. It's not a case of waiting for minutes, those would have already been received (within 30 days of meeting). Something else is going on, and I highly suspect the FDA have gone back to work out how a regulatory pathway would work through a opioid-sparing route. If you look at the guidance issued by the FDA in Oct20 (Opioid Use Disorder: Endpoints for Demonstrating Effectiveness of Drugs for Treatment Guidance for Industry) on the type of endpoints sponsors could use... remembering that in Mesoblast's Phase 3 trial clinicians and patients were told to
not change their existing treatments i.e. if they were using opioids, keep using them throughout the trial. What Mesoblast saw was that a significant number of patients, against the advice of their clinicians and Mesoblast, chose to stop using opioids.
Also keep in mind that accelerated approval can be gained through surrogate data.
Now have a read of one of the suggested clinical endpoints the FDA has provided the industry guidance on (OUD = Opioid use disorder):
"C. Change in Drug Use Pattern
FDA generally accepts change in drug use patterns as a surrogate for the benefits of abstaining from drug taking or for the presumed benefits of reducing drug taking. Change in drug use pattern is the most commonly used endpoint in registration trials for drugs in development to treat OUD. Sponsors have used it successfully to provide support of efficacy for all approved products for treating OUD. Sponsors have used a variety of approaches to evaluate drug use patterns. FDA recommends that sponsors compare percentage of responders rather than group means. One method is to define a responder as a patient who reduces the use of opioids to or below a threshold known to be associated with clinical benefit. (how about stopped using it completely... against the advice of the clinician no less)A successful trial would show either a higher percentage of responders in the treatment arm (for superiority trials) or noninferiority in the percentage of responders (for active-controlled noninferiority trials). A commonly used definition for a responder is abstinence, defined as no detected or self reported use during the specific assessment window. It is not possible to have absolute confidence that a responder achieved complete abstinence. Very frequent measurements provide more assurance of a substantial reduction in drug use, whereas infrequent drug use measurements result in greater uncertainty about the true magnitude of reduction in drug use. For this reason, absence of positive urine drug tests, absence of self-reported drug use, and attendance at frequent scheduled observations for these measures are components of a complete abstinence response definition....."
"I know that the Mesoblast people strive for success, not merely for themselves, but because we all want to be part of solutions that save lives, particularly those of children." I thank you and your team Silviu.
(20min delay)