The Story of Idelalisib

Our LATEST in @JAMAInternalMed
FDA was aware of a SAFETY signal for Idelalisib in 2016. The drug remained on market till 2023!

Meanwhile trials failed & were halted, millions earned, & safety signal mounted.

Horrible @FDAOncology failure 👇
See 🧵https://t.co/PxNH7Y4O2t pic.twitter.com/M7bhHVyxwl

— Vinay Prasad MD MPH (@VPrasadMDMPH) March 26, 2023

The story of idelalisib began btw 2008 and 2014 when multiple, (mostly) uncontrolled trials led the @FDAOncology to approve the drug for CLL and FL based on shrinking tumors on CT scans and not living longer or better pic.twitter.com/s16GNzuGUI

— Vinay Prasad MD MPH (@VPrasadMDMPH) March 26, 2023

Then in the years that followed, multiple trials had safety concerns, leading to a warning. pic.twitter.com/anG5BLgZCK

— Vinay Prasad MD MPH (@VPrasadMDMPH) March 26, 2023

In fact pic.twitter.com/qahH0bt9Eu

— Vinay Prasad MD MPH (@VPrasadMDMPH) March 26, 2023

Yet, @FDAOncology allowed the product to remain on market till "voluntary" withdrawal in 2022

During this time many more trials were launched pic.twitter.com/s2p6nzYydu

— Vinay Prasad MD MPH (@VPrasadMDMPH) March 26, 2023

Here is what is concerning. This is a cumulative meta-analysis of harm

Remember FDA did not take stronger action in 2016
Look at Serious adverse events rise and look at sales in millions pic.twitter.com/eNRYUY4byY

— Vinay Prasad MD MPH (@VPrasadMDMPH) March 26, 2023

Look at fatal adverse events pic.twitter.com/AUguKpi3WI

— Vinay Prasad MD MPH (@VPrasadMDMPH) March 26, 2023

Now look at deaths
The confidence interval is narrowing, but it is not on the good side pic.twitter.com/lLs1v34Ihx

— Vinay Prasad MD MPH (@VPrasadMDMPH) March 26, 2023

We describe 5 key findings
1. Less than half of studies are RCTs
2. Most trials remain UNPUBLISHED
3. Phase 3 data available were consistently CONCERNING
4. Product was withdrawn after addition 6! years on US maker
5. Company kept earning pic.twitter.com/XU6ojtLrNk

— Vinay Prasad MD MPH (@VPrasadMDMPH) March 26, 2023

Could the product have been withdrawn sooner? pic.twitter.com/8DGLbleNFE

— Vinay Prasad MD MPH (@VPrasadMDMPH) March 26, 2023

Also why did the FDA continue to approve multiple next in class drugs??

we discuss elsewherehttps://t.co/iZS5hnIgsm pic.twitter.com/mBHWDEbuwj

— Vinay Prasad MD MPH (@VPrasadMDMPH) March 26, 2023

This project was funded by @Arnold_Ventures

All credit should go to Titas Banerjee, MD
We actually had a plaque made for her for just how much effort this took. I will update this thread with a picture of that plaque

— Vinay Prasad MD MPH (@VPrasadMDMPH) March 26, 2023

Everyone should read the paper because this is about an FDA who is hungry to approve products, but has no appetite to regulate after approval

It consistently delays post market studies, and fails to take safety seriouslyhttps://t.co/PxNH7Y4O2t

— Vinay Prasad MD MPH (@VPrasadMDMPH) March 26, 2023

Pls draw attention to this important paper and issue

And remember FDA has not made Pfizer complete the post marketing myocarditis study in young men to date.

How is that acceptable?https://t.co/PxNH7Y4O2t

— Vinay Prasad MD MPH (@VPrasadMDMPH) March 26, 2023