Hy’s law

[rccola335]

I have not chatted a chance to read through all of the documents, but supposedly the FDA said there are two cases of hy’s law in imetelstat arm - this according to Fauerstein - supposedly Garon submitted documents from a liver panel of experts that disagreed with this

[Hoosier Investor]

I haven't seen what you're referring to, but we had an official (and positive) report submitted on this very topic....with no cases of Hy's Law observed.
https://www.regulations.gov/comment/FDA ... -0016-0004

[rccola335]

https://x.com/adamfeuerstein/status/176 ... CXgoldHN1Q

Not a fan of his

[jayfish101]

Thank you for jumping in, Hoosier! Strange that ODAC posts the negative but not the refuting study.

[jayfish101]

So I bought back most of my previous position now at a lower price than I sold. White knuckle time continues.

[Hoosier Investor]

Here's the full & exact language in the FDA summary....

"Two events meeting the laboratory definition of Hy’s law cases were observed in the imetelstat arm. Of these, one was in a patient who had abnormalities in bilirubin at baseline and had no clear pattern of worsening during treatment. The other patient developed transaminase and bilirubin elevation while being treated with imetelstat and deferiprox simultaneously. The abnormalities resolved when both medications were stopped and recurred after restarting first imetelstat then deferiprox. The Applicant attributed the abnormalities to deferiprox, but the timing of the dechallenge and rechallenge events makes attribution difficult."

Observations:
* The first (cited) patient had the condition upon enrollment, and the situation did NOT worsen during treatment with Imetelstat. This appears to be a positive outcome & data point for us.

* The second (cited) patient's condition seemed to have worsened as a result of either Imetelstat, deferiprox, or the simultaneous treatment by both. Geron has argued the condition was a function of the other medicine (deferiprox), but their argument hasn't (thus far) convinced the FDA. If Geron's data & expert arguments don't persuade, then it would seem a potential case for a label warning or use restriction.

[LWS]

Posted by FDA (Feb. 26, 2024)

There were no Hy’s Law cases. Two patients had both post baseline elevated bilirubin > 2 x ULN and ALT≥ 3 x ULN, i.e. potential Hy’s Law cases. These two cases were discussed in detail in quarterly HEC meetings. Hy’s Law criteria were not met because both patients had more likely alternative causes for the lab abnormalities. It is also noted that the peak bilirubin and ALT values were separated by more than one month which is not typical for an acute Hy’s Law Case.

[biopearl123]

I was blessed to have Hy Zimmerman as a GI professor when I was in med school. A key component to Hy’s law is “ No other reason can be found to explain the combination of increased aminotransferase and serum total bilirubin, such as viral hepatitis, alcohol abuse, ischemia, preexisting liver disease, or another drug capable of causing the observed injury.” This from Wikipedia. The panel of hepatologists were clear, no cases that met Hy’s law.

[rccola335]

Thanks - you all have made me feel better