Innovative leadership at FDA

[biopearl123]

https://x.com/i/status/2049198445454315759

[jayfish101]

Is this too good to be true? Sounds great. Also scary for insider information. The dream I think is that all people could access the ongoing data and we investors could make more informed decisions and so could patients and their families.

[huntingonthebluffs]

Well, I am becoming more cynical and jaded on how impossible it seems to get a worthy and desperately needed drug to approval. As far as I'm concerned, innovative leadership at the FDA is an oxymoron! I'm still waiting on using RWD to speed things up. How many years has it been since floating that bs out there?

Innovating the FDA takes so much more resolve than government can muster. If it is privatized, maybe. Of course that brings some baggage as well. Otherwise it's not happening IMHO.

I would be over the moon happy if the FDA could apply a little innovation to the ImpactMF P3 CT! Trying to be realistic but not likely happening as it takes a lot more than innovative leadership in government to make major change.

So if ImpactMF P3 is required to go to completion because the HR and p values didn't meet or beat P2 at the interim or whatever, due to additional time cycling through various Jak inhibitors delaying R/R status needed to qualify for the trial, followed by improvements in BAT and care quality once in the trial, then minimally, nearly every MF patient currently R/R to Jak inhibitors will die over the two additional years of trial without an opportunity to use RYTELO. Of course, many thousands of MF patients have already died without that opportunity due in part to trial design and FDA collusion (corruption basically).

If the DSMB and FDA can't logic through this correctly, I would conclude we continue to have a major issue with fairly applying common sense and ethics at the FDA. That won’t change until the underlying healthcare mafia running the FDA for ages is removed to allow innovative leadership a chance. Of course, aggressive and bold leadership at Geron could also be invaluable at cutting to the chase but a house cleaning at the FDA must happen first.

Of course, we all can see the writing on the wall. If the trial has to go to completion 2H28 before applying for approval, RYTELO's value to both patients and investors will be significantly impacted along with patent protection longevity. Also this continues to allow competitive alternatives more time to advance and further reduce value as well. IMHO, major investment entities will not likely just stand by and wait this one out.

However, given we have watched this drama for nearly 15 years, common sense needs to step up and maybe even take a whack at proving innovative leadership is more than bluster. Finding HR and p values are say, within some reasonable range of perfect, then logic, fairness and ethics says Geron should be allowed to proceed with the registration process. How can waiting 2 more years be remotely ethical given thousands of current and many future R/R patients won’t live that long?

If changes to treatment have occurred, changes to primary endpoints should be considered and made as well. Innovative leadership has to consist of more that just cutting out the “dead time” (not a pun). Adding warnings to the label and strict guidelines on how to qualify and continue on treatment could provide a level of protection. Just figure it out and stop playing God!

If the data monster absolutely must be fed, continue the P3 or require a P4 to finalize the HR and p values but get on with the registration now.

After all, I personally doubt this is likely but even if living 2-3 times longer on RYTELO than BAT is determined to now be 1.5-2 times longer on average, due trial changes, what patient wouldn't want that additional time. I may be a layman but a lot of this is not the rocket science we are making it out to be.

[biopearl123]

Hunt, it was probably just wishful thinking on my part. FDA would never allow study parameters to change during the study no matter what else was going on in the real world. Those are established at the beginning and must be strictly adhered to. The suggested FDA flexibility could only apply to future studies. I suppose two things could be true re IMpact, the study “stops” at interim and FDA allows priority review which could be done in record time, and the study continues as a P4 like IMerge to allow even more “fulsome” (to quote an unnamed source) data.

[huntingonthebluffs]

We all know rules are very important, especially in the CT setting. However, I would never say never and my 80+ years have taught me that every rule can have an exception. When circumstances are significantly different, exceptions can and need to be the rule.

Here we have a drug that is known to work amazingly well and we are nearly 6 years into an 8 year trial. But the trial has no clearly defined end date, 8 years is only an estimate, and the trial is the only one of its kind for MF ever. How can it be ethical let alone rational to not allow adjustments to successful exit criteria?

If our only option is to rely on the mathematicians and statisticians to be able to demystify all the tweaks that have occurred in the MF treatment landscape since the trial began along with crossovers, in order to demonstrate equivalent HR and p values, we are beyond ignorant. At some point common sense and ethics must guide rational decision making. And I do realize how challenging such a thought would be for the FDA.

At this point in the process, how can you look an MF patient in the eye, who is R/R to Jak inhibitors with progressive disease and ethically tell them RYTELO won't be available for 3 more years or more? I guess if you haven't watched someone with MF die, you don't know how cruel and absurd that is!!

[Ryan]

That all sounds really nice but will not happen. Scientific method rules out any potential human bias, which includes compassion.

The overwhelming likelihood is for the trial to move to completion, the #s that generate from the data have to show up, overwhelmingly (p-value is essentially a calculation to define “overwhelmingly”). I will point out that the Phase II did have an overwhelmingly good p-value , I recall calling it “crazy” at the time…. However, as discussed this was against Real-world-data, where frankly patients are *not* treated as well or thoughtfully as those in a clinical trial ,,, and current therapies are working better with more in use (stated by company) than the Real World Data which I believe included like 2008-2018 outcomes, something like that.

Lastly, I’ll refute a previous message on some other thread, the stock is not necessarily dead for two years if the trial marches on… many other factors and the company is valued at $1 Billion, which I repeat feels like an abomination to begin with. Only thing for sure, we’ll see.

[huntingonthebluffs]

https://www.google.com/search?q=have+pr ... fId=ChxjMe

[biopearl123]

Hunt, thank you for pointing this out. I was unaware this could happen . I would think changing parameters during a study might likely weaken it, for example going from an end point of OS to PFS. In the case of IMpact, one hopes the end point of OS is iron clad.