I don't think it was their fault that they chose the...

I don't think it was their fault that they chose the hospitalizations end point as the primary endpoint.

If you look at the current picture of HF treatments, it is frankly dismal. Even at the base line, I am sure you can name friends and family members who are on long term 'management' of CV conditions (e.g. post bypass surgery).

It is because HF is a many headed beast. There is no 'one' cause for HF. There are risk factors. Hence the quandary of selecting an appropriate primary end-point.

Look at what happened with Entresto. They shot for the % reductions in CV death, but their 13% relative reduction in the primary composite endpoint of cardiovascular death and total (first and recurrent) heart failure hospitalizations, narrowly missed statistical significance.

This is how hard it is for a trial to hit stat significance in something as huge as CV death.

Ironically, compare that with MSB's Revascor. Despite not hitting stat significance in hospitalizations, the 60% reduction in CV death (among other things when talking about MACE events) is an astounding almost 5x more effective than Entresto's results!

Let's take a slightly deeper dive. I'm feeling it.

If you read up about what Entresto is in addressing heart failure with reduced ejection fraction (aka HFrEF)

"Entresto is a twice-a-day medicine that reduces the strain on the failing heart. It does this by enhancing the protective neurohormonal systems (natriuretic peptide system) while simultaneously inhibiting the harmful effects of the overactive renin-angiotensin-aldosterone system (RAAS). Other common heart failure medicines, called angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), only block the harmful effects of the overactive RAAS. Entresto contains the neprilysin inhibitor sacubitril and the ARB valsartan"

If this means gibberish to you, let me break it down for you.

In a nutshell, Entresto blocks the hormones that causes constriction in blood vessels (causing you to hold on to too much salt and water) and also enhances the system that helps the blood vessels dilate - i.e. normal flow.

The elephant in the room is that Entresto, while doing this, does not address the size of the heart after heart failure.

Here's an interesting article on how this happens (if you don't know already) - https://www.uofmhealth.org/health-library/aa86963

This is the info in a little graph, courtesy of Dr Perrin.



As you can see, after heart attack, the heart basically compensates by enlarging (not a good thing.)

This is where Revascor, steps in.

If you recall what happened....



Look at what happens after Month 6 and Month 12! After administering Revascor, the LV end-systolic volume of the heart DECREASED. This is huge!

What it essentially means is that it reduces inflammation and improves microvasculature.

"The unchecked intra-cardiac inflammation in HFrEF patients causes progressive loss of heart muscle, replacement with scar tissue, and death. Persistent inflammation in the blood circulation also results in accelerated atherosclerosis with plaque progression and instability resulting in plaque rupture and potential blockage of major arteries. The net result is high rates of heart attacks and strokes in chronic HFrEF patients."

Though on the surface it looks like costly lesson, it was the right way forward that revealed a silver lining in the results. I would not be surprised if Novartis is already in talks with MSB to expand the partnership. If it can shell out USD9.7bn for Inclisiran, it can most definitely bankroll Revascor.