MSB - a new dawn, page-1557

Hi @nosluggos,

re " I don't think there has ever have been any misconceptions that Ryoncil is anything but "the treatment of last resort."", I trust you'll understand that I have to comment as I'm concerned that - in your effort to ensure that you have been fair & tolerant of others views (agendas) - you may, on reflection, see that you have conceded things which, in fact, are not the case & didn't need/ warrant - the concession. [PS: Kudos to you for being able to maintain the tolerant sentiment, but alas, I'm far less tolerant than you. Ha]

Yes, in prior years RYONCIL was used as salvage treatment. 100% true. That was in the past. Its use as salvage was, for example, the premise of protocol EAP275. But that salvage usage is no longer the case for paediatric SR-aGVHD.

Don't take my word for it, or that of any other HC:MSB posters.

The horse's mouth (i.e. FDA's) view on RYONCIL right now (which is the only one that matters, IMO) can be seen in this extract from the FDA's Letter Response of December 18 to the eminent Scott Lassman's "Citizen Petition" to stay RYONCIL's approval (viz at p. 16).

I encourage all MSB holders to read this section very carefully:




IMO there'sbeen more to be inferred from the December 18 letter response by FDA tothe Ctiizen Petition than merely its rejection i.e. the Petition's rejection,or even the FDA's clear statement of RYONCIL's trialled efficacy for paediatricpatients.

And I think one could even reasonably read into the FDA's comments some which appear to go beyond even the approval limitation i.e. the limit to 'pediatricpatients'. Have a close look at the points numbered #1. through #3. in the image above.

Why would the FDA allow that kind of inference to arise, I hear you say. Surely the FDA is a rules-based body solely focussed on just a proper dealing with the process in front of it, eh?

Well, the reason I say this is because I've thought, eversince the FDA letter response was published last December, that part of the background was that the FDA was pissedright off by the outright hubris & intellectual conceit in theobviously conflicting claims made by Lassman & Co. i.e. of some publicinterest in a Citizen Petition process (the primary aim of which on any reading seems to be nothing but express support for & effort to protect the commercial market for the drug JAKAFI) & (simultaneously) claim anonymityfor Lassman & Co's client. One wonders how Lassman couldeven keep his face straight in suggesting that there was any "public" interestin avoiding disclosure to the FDA of the conflcting interests of his monopolist client (no doubt Incyte Corporation). I mean, as if that wasn't apparent from the text of Lassman's submissions, there's this in his original 2020 submission:


How could Lassman submit economic information i.e. re damage or loss caused by RYONCIL's approval to "alternative, approved therapies on the market" without having express instructions from exactly the sponsors of those products. Sheesh. BTW, I don't think his principals could have been Novartis on its own simply because Incyte has sole marketing rights to Ruxolitinib in the USA, & IME every attorney in Incyte Corp's in-house legal division would have gone to war before allowing Novartis to argy bargy with & stick its fingers in the USA markets for Incyte products as it pleased.

As if that wasn't clear enough, there was also this solemn statement by Lassman that he has put his hand on his heart & has 'fessed up to the hidden things, like his thoroughly conflicted principal/ sponsor with commercial interests in JAKAFI, and yet no mention of what's in it for JAKAFI's sponsors anywhere in the "Citizen's Petition". Again, sheesh:



In any case, the FDA isn't full of idiots. They know an abuse of process when they see it. Now here they didn't call Lassman out on it at the time, AFAIK. But some of the comments by Director Wilson Bryan in his original note on the BLA file read remarkably similar to those of Lassman's presumed client, Incyte Corporation speaking through their sock puppet. Hmm. That kind of thing offends right-minded people, of which the FDA has many I'm sure.

And so we come to the December 2024 eventual denial of Lassman's "Citizen Petition". And here's where the FDA sinks the knife in up to the hilt, IMO, & says 'Run along now & take this 'ome to ya' mother'.

First, the FDA starts its dismemberment by quotiing Lassman's bloated overreaching claim set out on p. 16 in full - then it says " FDA disagrees with this assertion". Huh! But which of the parts exactly did it disagree with? Was it ALL of the assertion?

Did the FDA disagree about:
- the alleged absence of substantial evidence of efficacy of RYONCIL?
- the alleged risk of RYONCIL harming patients?
- the alleged risk to pediatric patients?
- the allged risk particularly to pediatric patients older than 12yo?
- the alleged potential delay or prevention of treatment with JAKAFI?
- the allegation that JAKAFI was the only FDA-approved treatment of SR-aGVHD in certain pediatric patients?

Well, it seems to me that the FDA unconditionally rejected Every. Single. One. of these obscene Lassman claims. And I say this because the FDA then goes on and spits it out, point by point, line by line.

It didn't have to do that, IMO, but it did. It could have rejected any portion of the 'logic' of the assertion e.g. re the absence of evidence of efficacy & left it at that to dispose of the issues, but it didn't. It rejected the entirety of Lassman's counterclaims, IMO. Line by line. Well, well, well.

So, at #1 the FDA first reiterates and backstops its determination that RYONCIL is both safe and effective in all pediatric patients - even if older than 2 months. So far it's predictably straight bat.

Then at #2, the FDA starts pushing the envelope. It makes a statement that is totally unnecessary to dispose of the "Citizen's Petition", IMO, but which is TOTALLY CONSISTENT with the FDA's ambition to deny an arrogant monopolistic drug sponsor a protected role in the USA healthcare system. It says " FDA considers patient access to a variety of safe and effective treatment options beneficial to public health.". Quite an innocuous way to say "FDA doesn't owe you anything Incyte, much less a monopoly. And you don't own us. Get off your collective rear ends and compete in the market for healthcare products that you wanted a license for. ". But it goes further, IMO @nosluggos. It implies at least an equivalent standard of proof between RYONCIL and JAKAFI as approved products in the eyes of the FDA. They're saying IMO "RYONCIL has jumped the same hurdles as you guys. Stop whinging".

All good. But then at #3, the FDA doubles down AGAIN & really goes offscript & lays into Incyte, as I see things. How else to read this?

"RYONCIL, a cellular therapy, may offer important benefits to patients, including those who may prefer not to use JAKAFI" !!

Where to start. OK, there was no need for the FDA to insert the words "a cellular therapy". They'd already made their Petition review point about 'variety' in treatments in the previous sentence. They're starting to get pointy now, IMO. It's almost like a turf defence: CBER protecting their own CBER-approved cellular therapies against an attack by one of CDER's approved drugs. Incyte may not have thought this one through very carefully. But lets not jump to conclusions. Let's say they were just pointing out that RYONCIL is not a drug. And might have different effects. OK.

So then the knife goes in - the FDA notes that "patients" (not even limited to 'pediatric' patients - suck on that Incyte) might just prefer not to use JAKAFI. Oh, because - I don't know - perhaps because they "offer important benefits". Like OS. Like mortality risk reduction. Like lowered morbidity risk. Like lesser risk of disease progression. Or relapse. Y'know, just 'benefits'. Being cellular and all.

And then the snapper - FDA says "Y'know, stop. Stop. What are we thinking. It's all good here & you Incyte - sorry, Lassman - don't need to worry about any of this. Because the patient's own physician & the patient will decide if these benefits are important.
So, not your worry.
Ta ta. Byeee"

What I'm seeing here is an FDA very happy to see RYONCIL used as a treatment for older (>17yo) pediatric patients even when they might be also be eligible to use JAKAFI.

Food for quite a bit of thought, IMO.

Cheers
GLTALTH