The FDA Is Too Aggressive About Blocking Life-Saving Drugs
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When my friend Ira was diagnosed with Pancreatic cancer he went through surgery and chemotherapy, but was still facing a short life expectancy. Then he was lucky to be 1 of only 26 patients in an early phase clinical trial of a drug called Ipafricept made by a start-up called Oncomed. Ira did well, as did 81% of the patients who got the drug.  He was soon free of cancer and is thriving today, over 8 years later. But soon after the trial was completed Oncomed ran of funds and closed, and development of this life saving drug halted. In the intervening years over 400,000 Americans have been diagnosed with Pancreatic cancer, and most have died or are dying.  I can’t say for sure, but I believe that this awful cancer would have claimed far fewer lives in those years if Ipafricept had received broader support, especially after it was shown to save precious lives.

An analysis in Forbes magazine estimates that each new drug represents an expenditure of over $6 billion, and for new cancer drugs the number is even higher, especially when treatment includes the latest technology. This reflects the cost of discovery and of failed attempts, which are unavoidable in the world of science, but also includes the cost of compliance with the Food and Drug Administration’s approval process which has increased precipitously over the years.

FDA approval is designed to dispassionately evaluate safety, dosing, favorable effects and adverse effects. It depends on randomized, controlled clinical trial studies to assure consistent scientific standards in all cases. And approvals are generally qualified by explanations of risks to help guide informed decisions to use or not use the drug. Sounds great, right?

Unfortunately the process is rarely dispassionate, and it seems to favor the wealthiest companies. This year the point was clear in the case of Leqembi, a newly approved drug which slows, but does not cure, the progress of Alzheimer’s. In the final clinical trial results before approval there were some severe side effects and three patients died. Nonetheless the FDA championed the drug by providing its accelerated approval process, and then gave full approval despite the side effects and deaths. The agency did require a label warning that Leqembi can cause ARIAs (amyloid-related imaging abnormalities), however the understated text fails to disclose the most concerning potential effect, severe brain bleeding. Put succinctly by Dr. Alberto Espay, Chair of the Gardner Neuroscience Institute at the University of Cincinnati , Leqembi “is neither safe nor effective, and, in the end, it may not justify the means…”

Meanwhile Biogen, the company commercializing Leqembi in the US, is charging forward with a sizeable investment of their resources to quickly generate profits, armed with their FDA approval, with Medicare footing most of the bill, and with target patients whose condition may impair their judgment. And their rich competitor Eli Lilly is close behind, also investing heavily in their monoclonal antibody donanemab, which appears to have similar effects and outcomes. For these financial powerhouses, the FDA approval process has not been too expensive, and the FDA has applied their standards liberally.

There are also smaller companies moving forward with less working capital but with drug candidates that show fewer and milder side effects. Can the FDA do more to facilitate approvals for these companies than it is currently doing? The answer is a resounding yes.

Annovis Bio’s candidate buntanetap is one such treatment. It is a daily pill with no demonstrated side effects in early testing. The drug blocks protein plaques before they are formed, and patients showed improved cognition in Phase 2.

And there is BioVie’s candidate NE3017, a twice daily pill, which showed no side effects and has concluded Phase 3 testing. The early data released to the Alzheimer’s research community shows patients with significantly improved cognition, and with reduced signs of the disease in the brain.

For drugs like Annovis’s and BioVie’s, FDA approval and safety guidance should of course require sound scientific evidence. However the agency has shown that it can accelerate or prolong the process at will. When early results warrant, and especially when lack of funds could rob patients of a promising treatment, the agency must look for ways to champion the drug and help it get to the decision table.  There is no way to know if any kind of FDA championing could have saved Oncomed, who made my friend Ira’s drug, from insolvency. But we do know that innovative breakthroughs are not reserved for pharmaceutical giants.  And when breakthroughs suffer or die, patients suffer and die too.

Ken Blaker is a Los Angeles-based healthcare and technology consultant focused on medical devices and FDA compliance.

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