Accelerated Approval - read b/w the lines

Hi all

I have taken some time to sit and think about what yesterday's announcement means. It firstly struck me as odd... and something that MSB wouldn't normally do. So I had time to ponder it today... here are my thoughts.

Firstly RMAT has been thrown around quite a bit recently and I wanted to point out that RMAT is a designation that allows priority and more frequent discussions/reviews with the FDA that could lead to accelerated approval. However it is not necessary for accelerated approval, although it would IMO make it much easier.

IMO it would be logical to get RMAT designation before trying for accelerated approval. Although RMAT is not mentioned in the announcement, I would be surprised if MSB have not already or will not shortly lodge a request for RMAT designation.

However I wanted to explore was what prompted the announcement by MSB to come out and say they had a potential pathway to Accelerated Approval. And at first glance the announcement may sound like a weak one ... with the use of 'potential' in the heading ... but think of this:

1) If not a 'potential', what else could they have said? For any lodgement for accelerated approval with the FDA is only a potentially accelerated approved product.

2) MSB have been very tight lipped on the CHF program since (and even prior) to Teva handing the program back. In fact just prior to Teva leaving the program - they were due to give us an update on the 'pathway' for the CHF program.

So what I take out of this is that accelerated approval is like jumping the a very very long queue. If successful it will bring forward the commercialisation of a product by several years. The key take-away is that MSB are now actually committing themselves to going for accelerated approval. This is actually a very significant development in my eyes ... and has sparked an interest into why now?

Why after all this time... does MSB announce that they have a 'pathway' for the CHF program for accelerated approval?

In my mind, there is no doubt that something has happened in the background that has given MSB confidence that they are now able to achieve accelerated approval. We know that MSB have been in discussions with the FDA for a while now ... did the FDA given MSB a positive sign?

To explore what I believe could have happened ... firstly what does Accelerated Approval actually mean and how is it granted, a good place to look to understand this is the FDA website. Link to the relevant page is below:

FDA Accelerated Approval

In summary the FDA can approve treatments such as MPC 150-IV for treating CHF patients based on surrogate /intermediate clinical endpoint from its previous phase 2 trials + the upcoming NYHA sponsored LVAD trial reading out in Q1 or 2018.

The example given in the FDA website is that accelerated approval may be given to a cancer drug if the sponsor demonstrates that the drug shrinks the size of the tumour (surrogate endpoint), without demonstrating that the lifespan of the patient is extended (primary endpoint) - because tumor shrinkage is considered "reasonably likely" to predict a real clinical benefit.

It is generally accepted that heart failure may be due to either systolic or diastolic dysfunction of the left ventricle, and is referred to as heart failure with reduced ejection fraction or heart failure with preserved ejection fraction, respectively.

So similarly for MSB, a comparative surrogate endpoint may be demonstrated improvement in left ventricle systolic and diastolic volumes, which we know have been shown in the trials to date and may be further supported by the NYHA trial to read out in Q1 of 2018.

As I said above - what has got me thinking is what could have triggered the announcement yesterday. Some may say it is to spruce the market prior to a CR... but it is a highly unusual announcement if that was its intention. It was very  conservative in how it worded and articulated... if they really wanted to get the market excited, they would have worded it very differently. Rather it was a relatively reserved announcement.

Personally I believe it is very plausible that MSB have been able to agree in principle with the FDA through discussions to date that an improvement in a particular surrogate endpoint/s could be "reasonably likely" to predict a real clinical benefit for CHF.

That to me would be something that would given MSB enough confidence to say that they will be discussing accelerated approval with the FDA. MSB could have come out and said this a year ago ... but they chose to announce it yesterday.

I don't believe they would have put themselves out there without FDA giving them a nod. Accelerated approval is a very high bar to meet ... with very significant benefits if successful. It is not something that companies apply for with blind hope, they would have to have established strong grounds to believe that the FDA would give them approval.

I expect Silviu will go into this in a little more detail at the annual results presentation next week.

Good luck all!