How tough should the U.S. Food and Drug Administration (FDA) be when approving drugs? Currently drugmakers must not only show their drugs are safe (Phase 0 and Phase 1 trials), but also, they have the desired effect on the body for most people (Phase 2 and Phase 3).
A few weeks ago, two scholars wrote an opinion piece in the Wall Street Journal arguing drugs would come to market much faster if their developers only had to prove safety, but not efficacy. I wrote about it here. I argued that if drugmakers did not have to prove their drugs work (what I called conditionally cleared to market), then health plans should have the option of refusing to reimburse for them. If a drug works well, most health plans willingly pay for it. If the drug worked poorly, then they would not. My idea was to create an incentive for drug companies to accumulate real world data to get their drugs fully approved rather than conditionally cleared to market.
Yesterday a drugmaker complained that the FDA moved the goalpost on them making their (hyper expensive) drug take longer to gain approval:
The biotech firm UniQure on Monday reported that the FDA had moved the goalposts for approving its Huntington’s disease gene therapy. There are currently no approved drugs that can slow progression of the brutal neuro-degenerative disease, which afflicts about 40,000 Americans. The FDA in April designated UniQure’s treatment a “breakthrough therapy.”
The agency also previously said UniQure could apply for accelerated approval if its drug showed statistically significant benefits with three years of data, and its trial could include an external control group that didn’t receive a placebo. The gene therapy’s administration requires brain surgery, so a placebo arm isn’t practical.
UniQure reported in September that its treatment slowed progression by 75%. Hold the hallelujahs. UniQure said Monday that the “FDA currently no longer agrees that data” are “adequate” for approval. That means UniQure might have to run another trial with a placebo group, which could take several years, if it can even find patients who will volunteer to receive a placebo.
At the heart of the complaint is that the FDA executives whose job it is to oversee the approval process and decide whether some therapies receive expedited reviews are too paternalistic.
Dr. Tidmarsh shares Dr. Prasad’s regulatory paternalism. He has criticized the FDA’s past leaders for “endangering patients” by approving drugs that “gave them false hope,” and “cost vast amounts of money that our health case [sic] system can ill afford.” In September he called for a reappraisal of the FDA’s accelerated approval process.
A little over four years ago the FDA buckled under pressure and approved Aduhelm, a monoclonal antibody for early-stage Alzheimer’s disease. Supporters argued it was the only new Alzheimer’s drug in many years. However, critics later claimed it was a hyper expensive drug that barely worked with severe side effects (e.g., brain bleeds). The drug has since been withdrawn from the market.
I have criticized many drugs as being hardly better than a placebo. Years ago, I ran across a website (now defunct) that allowed people to rate the drugs they take. Viagra rated high, something like 4.5 out of 5. By most accounts it worked well but some people complained about its side effects. Nonsedating antihistamines rated poorly. I forgot the exact rating, but it was something less than 2 out of 5. In recent years I have even heard some experts say antidepressants hardly work better than a placebo.
The question remains: how much scrutiny should the FDA exert on novel therapies when the benefits are less than clear, the side effects not fully known and the cost is likely through the roof? The FDA has traditionally not taken cost into account, but this may be changing under the Trump Administration. Should it make any difference if the disease populations are small, like an orphan drug? It is easy to criticize drug approval after-the-fact when a mostly ineffective drug is expensive. However, the other side of that coin is how many drugs are we likely to miss out on due to rigid standards for efficacy. It is not an easy decision.
Read more at WSJ: The FDA’s Meltdown Escalates
Certainly, there should be a standard of effectiveness for drugs paid for by Medicare or Medicaid, which private insurers allowed to follow the same standard.
But for people paying out-of-pocket or for off-label uses I can see leaving it up to the consumer.