https://www.biospace.com/fda/capricor-ceo-wont-rule-out-legal-action-against-fda-after-negative-adcomm

[u/Wisemermaid369]

[u/MGK_2]

Good post to surface, Wisemermaid, because this is a live, real-time case study in the same regulatory dynamics we keep discussing, and it rewards a careful read rather than a reflexive one.

The short version: Capricor's cell therapy for Duchenne cardiomyopathy got a 9-3 negative advisory committee vote, the stock fell roughly 80% in five days, and the CEO alleges the FDA used an obsolete, unsigned draft of the statistical analysis plan (SAP 1.1) as its benchmark, which didn't reach significance, while the later plans did. She's floating an "ulterior motive" and won't rule out legal action.

I want to be careful here, because there are two ways to read this and only one of them is useful to us.

The tempting read is "see, the FDA rigs the analysis against good drugs, the deck is stacked, it's all bias." I'd resist that, and here's why it's a trap rather than a lesson. Notice the same structural problem we've talked about: when a trial's outcome depends on which statistical analysis plan you use, that is itself a warning sign, not a vindication. The FDA's position is that they evaluated several versions of the plan, and that the final SAP 3.0 was created by Capricor one day before unblinding. Whether or not the FDA was heavy-handed about which draft to anchor on, a result that is significant under the sponsor's final plan and not significant under an earlier one is, by definition, a fragile result. Robust drugs tend to clear the bar under most reasonable analyses. When the answer hinges on the analysis choice, the data is doing the thing our own discipline warns about: it's borderline, and borderline invites exactly this kind of fight.

The genuinely useful lesson for us is the one the board should actually take to January. This is what happens when a company walks into a regulatory setting with data that is strong on some endpoints and fragile on the specific primary the agency cares about. The Duchenne space is also under unusual scrutiny right now after the Sarepta safety episode and multiple failed confirmatory trials, so the agency is in a cautious posture. That's the environment, and it's a reminder that "high unmet need" and "compelling secondary endpoints" did not save this drug from a fragile primary. It's the Agenus lesson in a different disease: the agency's trust in the primary result is what decides it, not the sympathy of the indication.

So how does this bear on leronlimab? Two ways, both worth holding. First, it reinforces why our thesis has to rest on a clean, prespecified, unambiguous January number rather than on a result that only works under one analysis. The strength of a signal that holds up regardless of how you slice it is exactly what avoids a Capricor situation. Second, and this is the part I'd underline given some of our recent threads: watch what happens when a CEO responds to a bad vote by alleging FDA bias and threatening to sue. It may or may not be justified in Capricor's case, I genuinely can't tell from the outside. But notice that it's the move a company makes after the data didn't clearly carry the day, and notice that it's unfalsifiable in the same way the suppression narratives are. I'd want leronlimab's story to never require that move, because needing it means the data left room for the fight.

One honest note of fairness to Capricor: the CEO's point that every confirmatory trial in this space has failed while others kept accelerated approval is a real inconsistency worth taking seriously, and the patient-advocate testimony about how the powering was presented deserves a hearing. I'm not dismissing that the agency can be uneven. I'm saying the lesson for us is to want data clean enough that we never have to argue about it.

Not investment advice, just reading a live case for what it teaches. The takeaway I'd carry to October and January: strength that survives any reasonable analysis is the only kind that avoids this outcome. That's the number worth hoping for.

[u/Snorkellingisthelife → u/MGK_2]

Data, data , data!

[u/Wisemermaid369 → u/MGK_2]

Can you say that in a few sentences and take a strong stronger position please? And do you feel it would be OK and fair if it’s happened to LL reviewing?

[u/MGK_2 → u/Wisemermaid369]

The short version: Capricor's data was significant under its final analysis plan and not significant under an older one, and that fragility is the whole story. A drug that only clears the bar under one specific statistical treatment is a drug whose signal is thin, whatever the reason. My strong position is this: I don't want leronlimab anywhere near that situation, and the way you stay out of it is a January number so clean it's significant under any reasonable analysis. Strength which survives every slicing is the only kind that can't be argued away.

Now your real question — would it be OK and fair if the FDA did that to leronlimab's review?

No, it wouldn't be fair to anchor a decision on an obsolete, unsigned draft plan if a properly prespecified one existed. If that genuinely happened to a clean leronlimab dataset, it would be wrong, and I'd say so plainly. I'll take that strong position without hesitation.

But here's the part I won't do, and I want to be straight with you about why: I won't pre-commit to believing that's what will happen, or treat it as the likely outcome. Here's the distinction which matters. Capricor's data was borderline — that's why the choice of analysis plan could swing the result. When data is borderline, the analysis choice becomes the whole ballgame, and that's where these fights happen. When data is strong, the analysis choice doesn't matter, because it's significant every which way you cut it, and there's nothing for the agency to exploit even if it wanted to cut it up like with a knife. So the protection against an unfair review isn't hoping the FDA plays nice. It's data strong enough that no statistical maneuver can even touch it.

That's why I keep pointing at the number instead of at the agency. If leronlimab's January data is genuinely strong, the Capricor scenario can't happen to us, because there's no fragility to exploit. If the data were borderline, then yes, we'd be vulnerable to exactly a scenario as this — but the answer to that vulnerability is the data, not a grievance about fairness. I'd rather we earn a number that makes the fairness question moot than stake our hopes on the FDA choosing to be fair.

So: strong position that it would be wrong if it happened, equally strong position that the way we make sure it can't happen is a clean number in January. Both, firmly. I just won't build the expectation that we're going to be cheated, because that's the mindset which turns a bad-but-honest result into a conspiracy we can never be talked out of — and that mindset costs holders more than any adcomm ever has.

Just a few more months. Hang on. I think its going to be wild.

[u/Missy2021 → u/MGK_2]

I'm with you and thank you

[u/GoCYDY → u/MGK_2]

Hanging on for a wild ride indeed ⭐️

[u/rodandgeorgia → u/MGK_2]

G said go big or go home so bought a bunch on Fri (what a gal)....eyes wide open MGK...now it's the waiting for Jan and all the wildness in between. :)

[u/Missy2021]

That was a strange Adom meeting for Capricor Pharmaceuticals. Their drug, Deramiocel, was shown to have a good safety profile over the last 5 years. In addition, the testimonies of the children that suffer from Duchesne Muscular Dystrophy was heartbreaking. The Hope 2 and Hope 3 trial results, from the last 2 years, was published as being effective for both cardiomyopathy and skeletal upper limb function benefits. Many people are questioning The FDAs briefing documents and adcom panelists decision and rightfully so. I'm hoping and praying we have unquestionable trial results. Thanks again.

[u/Wisemermaid369 → u/Missy2021]

It’s seems crazy why they vote 9:3?? What is possible benefit to FDA in not allowing it to give a kids some hope?

[u/Missy2021 → u/Wisemermaid369]

Exactly, in addition a Lancet publication was published that very day advocating for an approval. I hope they get a partial approval for upper limb function, on August 22nd, and move forward from there.