Ryoncil: ODAC/FDA Meeting Discussion, page-1930

So, after a nap, a nice long shower and coffee being made, here are my thoughts on the shindig that went down from 10pm to 7am.

Now, more than ever, have I learnt the true immuno-modulatory properties of our beloved Remestemcel-l.

To put it in a nutshell (as the Prof was very calmly re-explaining to the doubters), through a very rigorous manufacturing process, our cells are of superb quality because...

1) Everything to bring the cells to 'the shelf' has been done under stringent quality standards

2) Think of our cells as a smiley face , and the critical standards for it to be called a smiley face would be the happy eyes, and wide grin, that, when seen, makes you go, 'Ah! It IS a very high quality smiley face!' (For those of you more intellectually inclined, the happy eyes = TNFR1 expression, the wide grin = interleukin (IL) - 2Ra inhibition)

[Side note, I've always thought that a true smile is when you smile with your eyes as well, but I digress. ]

Next..

When there is INFLAMMATION (a frown ) , enter Rem-L !

Here's a very simple primer on how it works!

1) Rem-L smells a
2) Rem-L starts making happy eyes and wide grins

3) These then make downstream calm down

(Again, for those of you intellectually inclined, the expression of TNFR1 basically inhibits NF-kB and then the M1 macrophage gets polarized into an M2 macrophage which then causes IL-10 (which is an anti-inflammatory cytokine that plays a central role in limiting host immune response) to 'come out' = modulated immune reaction, simply put )

Now, currently

Our are flippin potent! 33% more happy eyes and 17% more wide grins whoa!

Let's take this knowledge and then talk about the two other drugs mentioned - ruxolitinib and infliximab

[IMO, I think bringing those two up were absolute silver bullets, but again, I digress ]

Some concerns with our 001 pivotal study was that it was -
1) Single-armed (basically not a randomized controlled trial)
2) Too few kids! 55 only! Gasp!
3) Day 28 OR (Overall Response) of 70.4% (with the 95% confidence interval range of 56.3 - 82 --> 25.7

Among other concerns..

But ohh... boy did ruxolitinib look so shaky...

It got APPROVED off it being (also) single-armed, 49 kids (lesser kids!) and Day 28 OR of.... 57.1%.. with a LARGER range of 42.2 - 71.2 --> 29!!!

One wonders HOW did Incyte even get this over the line????

Don't even get me STARTED on the side effects....

FROM THE JAKAFI WEBSITE (source: JAKAFI SIDE EFFECTS LINK )



HOLY F#$@ Read that line again! "THESE ARE NOT ALL THE POSSIBLE SIDE EFFECTS OF JAKAFI"

In a nutshell..

FDA: Oh no! No available options! Lets just go with yours cos you save lives. Never mind it being single-armed, u can sort that out later.

So when you look at Remestemcel-L, with an UNQUESTIONABLE safety profile and NO side effects side-by-side with ruxo...
One wonders why the FDA committee was so quick to dismiss any questions that alluded to their approval of ruxo.

I believe it was Dr. Sung who was asking the FDA crew about it, and he basically got a no-response about the standard of assessing single-arm trials given the proper context.

More thoughts about infliximab later! Or maybe I'll hand the baton to @LeftYahoo ?