Last week, the US FDA held a meeting to decide if a new surrogate endpoint (Minimal Residual Disease or MRD negativity) could be used to give more & faster drug approvals for patients with newly diagnosed multiple myeloma.
Multiple myeloma drugs can cost $600,000 per year of treatment, but if MRD is permitted for drug approval, I suspect we will see a deluge of uncertain drugs added to the roster, and the costs per year per patient will swell to a million dollars or more. Let’s be clear: that is not sustainable.
Yet, most present at the meeting cheered on the changes. Including:
The academic speakers— who often consult for the drug companies and receive sizable personal payments.
The patient advocates— whose organizations are often funded by drug companies.
The FDA — whose employees often leave to work at the drug companies.
In fact, there were so few critical comments at the meeting, and it was so one-sided that I wondered why the FDA held the meeting at all. Why not just push through the change clandestinely?
My biggest concern with the change wasn’t the cost however, but the safety risk. It can take several years for the full safety profile of drugs to be known. For instance, CAR-T was given to myeloma patients in 2014, but we only learned it can cause Parkinsonism in 2021. Another drug— teclistimab— causes bad infections, but these most often come 18-24 months after starting the drug.
Faster approvals means that many harms will be unknown when drugs are debuted to tens of thousands of people. Since myeloma patients can live 15 years or more— any neurologic damage or parkinsonism or blindness— is a catastrophic risk.
I was given 5 minutes to speak at the committee and these are a version of my remarks. Take a listen. I make 5 points why this is a bad idea.
Unfortunately, my comments were largely ignored at the meeting, and tired talking points in favor were offered. One speaker suggested that the change might lower drug prices because companies would have longer patent lives to earn back their losses. This is economically illiterate thinking. Of course, the companies will earn much more money if the change goes through— the market share is colossal— that’s why they support it!
Another speaker said that a good initial response does predict a longer life with myeloma. That’s also incorrect. The FDA’s own analysis showed that, across trials, MRD negativity was a poor surrogate for overall survival, failing to meet the pre-specified bar. Some observers got it:
Some speakers at the FDA meeting talked about the change as important as it grants access to new drugs, but that is also not true. I am not aware of any drug being tested in the frontline of myeloma that is not already on the US market for relapsed disease. Doctors are already allowed to prescribe these drugs (off-label) in the front line. In fact, the FDA’s accelerated approval won’t grant access to new drugs, but rather, I fear, is a grand strategy to force insurers and Medicare to pay for these uncertain drugs.
Some speakers represented patient advocacy organizations and later lashed out at me on twitter. Curious, I looked to see who supported the organizations. Guess who?
Not only is this new change a risk to patient safety, it is yet another straw on the back of American health care. We spend ~20% of our GDP on health care, and that number is rising each year. This is often money that is not voluntarily spent, but coercively taken in the form of taxes and employer-based insurance subsidies. As a result, the real take home wage of Americans has stagnated since the 1970s leading to palpable anger, and this is money we don’t spend on preventive care or better nutrition and education for children.
What am I to think when the FDA holds a meeting where the conclusion seems pre-ordained? Where many of the presenters consult for pharma? Where many FDA employees will soon work for pharma? Where patient groups are funded by pharma? And all this— where meeting materials are only given to the public 2 days before— not enough time to scrutinize? Critics given only 5 minutes to speak?
What’s certain is the decision will enrich pharma. What’s uncertain is if patients will be better off. The sad part is we won’t ever know, as the FDA has largely absolved itself of the duty to ensure these drugs improve overall survival (see video), and will settle for progression free survival— another surrogate— to convert to regular approval.
While I am sure most doctors and patient advocates are good people; good people can do bad things in a broken system. The current system is broken. It will bankrupt us, and exposes sick and vulnerable people to considerable risk. Medicine has become a financial commodity with the rare adverse event of better health outcomes.
It is a shame that many do not see how they are complicit with one of the biggest threats to America. We will go bankrupt spending money on drugs that change laboratory values, but which we have no clue if they make people better off. A few companies will get rich doing this, and many well-intentioned people will be cheering us over the cliff.
Vinay Prasad, Hematology Oncology Medicine Health Policy Epidemiology Professor
https://www.sensible-med.com/p/unproven-healthcare-will-bankrupt
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