NASH a No Go

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anonymous

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From Page 1 and 2 of FDA briefing book, no need to read further, stick a fork in it.

The adverse reactions experienced with OCA 25 mg suggest that treatment with this dose exacerbates
co-morbidities or creates new ones for a patient population at risk for metabolic syndrome and its
manifestations. Specifically, OCA 25 mg-treated subjects, relative to placebo-treated subjects,
experienced:
• Hepatotoxicity: cases adjudicated by drug-induced liver injury (DILI) experts identified a serious
signal for DILI in the OCA 25 mg-treated subjects.
• Excess risk of cholecystitis and bile duct stones/sludge and related life-threatening complications
and surgical interventions.
•Excess risk of new onset prediabetes/diabetes requiring new treatment or poor glycemic control in
diabetic subjects that required additional anti-diabetic therapies.
• Substantial excess risk of dyslipidemia that required new treatment with statins or increased
dose/intensification of statins.
• Substantial excess risk of severe pruritus leading to treatment-interruptions, administration of
antipruritic agents/bile acid binding agents/corticosteroids, or drug discontinuations.
• Excess risk of developing acute kidney injury.
 












anonymous said:
From Page 1 and 2 of FDA briefing book, no need to read further, stick a fork in it.

The adverse reactions experienced with OCA 25 mg suggest that treatment with this dose exacerbates
co-morbidities or creates new ones for a patient population at risk for metabolic syndrome and its
manifestations. Specifically, OCA 25 mg-treated subjects, relative to placebo-treated subjects,
experienced:
• Hepatotoxicity: cases adjudicated by drug-induced liver injury (DILI) experts identified a serious
signal for DILI in the OCA 25 mg-treated subjects.
• Excess risk of cholecystitis and bile duct stones/sludge and related life-threatening complications
and surgical interventions.
•Excess risk of new onset prediabetes/diabetes requiring new treatment or poor glycemic control in
diabetic subjects that required additional anti-diabetic therapies.
• Substantial excess risk of dyslipidemia that required new treatment with statins or increased
dose/intensification of statins.
• Substantial excess risk of severe pruritus leading to treatment-interruptions, administration of
antipruritic agents/bile acid binding agents/corticosteroids, or drug discontinuations.
• Excess risk of developing acute kidney injury.
Click to expand...

wonder how all of the incredibly arrogant home office “leaders” will sparkle over this? Sure it’s only a recommendation but all will be settled by the advisory committee on Friday. In light of Madrigal’s data, there’s no need to approve our crap data for use.
 






anonymous said:
wonder how all of the incredibly arrogant home office “leaders” will sparkle over this? Sure it’s only a recommendation but all will be settled by the advisory committee on Friday. In light of Madrigal’s data, there’s no need to approve our crap data for use.
Click to expand...

or maybe during the advisory meeting it will give us the opportunity to address the concerns.
 












anonymous said:
or maybe during the advisory meeting it will give us the opportunity to address the concerns.
Click to expand...

LOL!!!! Address concerns? We had years to do that along with the data disclosures in the run up to this mtg. But sure, let’s hang our diminishing hopes on the outcome of this meeting! Sheer lunacy or perhaps arrogance in the fact that such a miserable job of KOL opinion and mkt development was conducted by our so called leadership. I can’t wait for the national call after this.
 






anonymous said:
LOL!!!! Address concerns? We had years to do that along with the data disclosures in the run up to this mtg. But sure, let’s hang our diminishing hopes on the outcome of this meeting! Sheer lunacy or perhaps arrogance in the fact that such a miserable job of KOL opinion and mkt development was conducted by our so called leadership. I can’t wait for the national call after this.
Click to expand...

You are one miserable SOB. I feel sorry for you.
 






anonymous said:
or maybe during the advisory meeting it will give us the opportunity to address the concerns.
Click to expand...

FDA would be doing a great service to Intercept to reject this drug for NASH. Think of all the money that would be pissed away on market development and sales for a drug that has absolutely NO rationale for reimbursement.
 






anonymous said:
FDA would be doing a great service to Intercept to reject this drug for NASH. Think of all the money that would be pissed away on market development and sales for a drug that has absolutely NO rationale for reimbursement.
Click to expand...


What about the patients that it has helped? That population needs something. There’s nothing in the market and Madrigal is not a slam dunk. Thoughts?
 






anonymous said:
What about the patients that it has helped? That population needs something. There’s nothing in the market and Madrigal is not a slam dunk. Thoughts?
Click to expand...

Who does it help? An 8.6% difference vs. pbo on improvement in fibrosis of at least 1 stage with no worsening of NASH and the drug failed on NASH resolution with no worsening of fibrosis. When you consider the risk of DILI, Kidney among the litany of other safety concerns, this doesn't even seem like a close call.
 






anonymous said:
Who does it help? An 8.6% difference vs. pbo on improvement in fibrosis of at least 1 stage with no worsening of NASH and the drug failed on NASH resolution with no worsening of fibrosis. When you consider the risk of DILI, Kidney among the litany of other safety concerns, this doesn't even seem like a close call.
Click to expand...

Tim you raise some good points. We will see what tomorrow brings. At this point let’s wait and see what the votes of advisory committee will be.
 












anonymous said:
LOL!!!! Address concerns? We had years to do that along with the data disclosures in the run up to this mtg. But sure, let’s hang our diminishing hopes on the outcome of this meeting! Sheer lunacy or perhaps arrogance in the fact that such a miserable job of KOL opinion and mkt development was conducted by our so called leadership. I can’t wait for the national call after this.
Click to expand...

Risk to benefit ratio is terrible and doesn’t justify any recommendation for approval not when a safer more effective product is on the way. I have been interviewing for a few weeks now. I suggest you all do the same.
 






























Out of 1000 patients in each group, deaths are 17 (oca 25mg) vs 10 PBO. This is terrible safety data. Risk/benefit ratio is looking worse and worse the more they discuss it. Most panelists not impressed. See you at the job fairs!!!!
 






anonymous said:
Out of 1000 patients in each group, deaths are 17 (oca 25mg) vs 10 PBO. This is terrible safety data. Risk/benefit ratio is looking worse and worse the more they discuss it. Most panelists not impressed. See you at the job fairs!!!!
Click to expand...

Adcomm chair Lenwohl “given the looming safety concerns our enthusiasm for the efficacy data is tempered” Yeah, sounds like we’re in the clear everyone!!! If Madrigal didn’t have such clean data we may have had a slim chance. In the immortal words of Larry David “Now, not so much”
 






Our defense for the cases of DILI is essentially “we know it’s directly toxic, not idiosyncratic tox, therefore the insult will stop when we remove the drug” What the heck are we doing here?!!! This isn’t going to be pretty.
 






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