2016 FDA drug approval numbers — what can Trump conclude?
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In 2016, the FDA approved just 22 novel new medicines, a six-year low and half of the 45 approved in 2015. That’s the top line bad news; unfortunately, there is a more disturbing message when one digs a little deeper.

Forty-one percent (nine of the 22 drugs) are intended for orphan or rare diseases. Eight of of these received Orphan drug designation (the cutoff to qualify for Orphan status is 200,000 patients per year). To this, I also included Anthim, an antibody for use in patients who have inhaled anthrax, since one would presume that the number of patients eligible to receive the drug in a given year, would be far less than 200,000.

Seventy three percent (16 of the 22 drug) received regulatory review incentives that are generally intended for drugs that address a significant unmet medical need or for which no other therapies exist. This includes breakthrough therapy designation (BTD), fast track, priority review, accelerated approval, or animal rule (requiring no clinical trials of effectiveness).

There is an expression, “The squeaky wheel gets the grease.” When it comes to the Food and Drug Administration (FDA), that is clearly the case. The FDA has made it clear that drugs intended for conditions that affect millions upon millions of Americans are not important.

Cardiovascular disease remains the number cause of death in the United States, yet, not one drug to treat primary cardiovascular disease was approved in 2016. Similarly, there were no drugs approved to treat obesity or Alzheimer’s disease, and just one for diabetes. These are conditions that are afflicting Americans in epidemic proportions and which cause tremendous morbidity (sickness) and mortality (death). This is shameful.

Critics of my position will say that the FDA cannot approve that which drug developers are not developing and submitting for approval. This is precisely my point. Drug developers are like electrons — they follow the path of least resistance.

Continuing the metaphor, the reason that drug companies are increasingly focusing on rare and specialty diseases is because the path to development for these is much easier than the path for diseases that affect millions of Americans. The serial resistors for the latter are long, large, expensive trials that must demonstrate effects on clinical outcomes and survival; the parallel circuits are the onerous post-approval study requirements that frequently constitute re-adjudication of the initial approval decision.

Why bother developing drugs for diabetes, cardiovascular disease, obesity, and Alzheimer’s disease when, instead, the FDA is offering shunts in the circuit in the form of regulatory incentive programs for drugs that affect far, far fewer Americans. And, these drugs command extremely high prices. For example, Biogen’s Spinraza for spinal muscular atrophy (SMA) will be priced at $750,000 for the first year.

I just returned from the Biotech Showcase (BTS) in San Francisco where I had the honor of chairing a panel —The New Administration: What to Expect from the FDA.

I made the point that the list of presenting companies at the 2017 BTS included 95 percent that are developing cancer drugs and just three developing drugs for diabetes; this was about the same ratio of drugs approved in 2017 for cancer (four) and diabetes (one).

That got their attention, but the audience was truly stunned when I stated that Adlyxin, the single diabetes drug that was approved, required eleven clinical studies including over eleven thousand patients, one of which was a four-year trial in 6,000 patients.  On the other hand, Tecentriq, a drug for refractory bladder cancer, was approved on the basis of a single non-randomized trial in 310 patients. Nine of the trials for Aldyxin were randomized. Aldyxin benefitted from no regulatory incentive programs, while Tecentriq received BTD, priority review, and accelerated approval.

If you were an investor, what company would you prefer — a drug for a rare disease for which various regulatory incentives have been granted or a drug for patients with heart failure or diabetes for which multiple, large, long-term randomized controlled trials are needed pre-approval and post-approval?

The answer is simple, and since investment is the lifeblood of innovation, we see why there was no innovation in cardiovascular disease, obesity, or Alzheimer’s disease this year.

Don’t get me wrong, I want more drugs approved for all conditions – niche, rare, hard to treat, as well as for common diseases killing millions of Americans. The way to fix this problem is with effective strong leadership at the FDA to change the culture or fear that has driven the shift to rare disease approval.

The FDA’s mission, as stated in the Federal Food, Drug, and Cosmetic Act (FD&C), is to promote health by promptly and efficiently reviewing clinical research and taking appropriate action on the marketing of regulated products in a timely fashion. This is supposed to be for all drugs that are safe and effective, not just those qualifying for regulatory incentives.

The solution is to return FDA’s focus to safety and effectiveness. Right now, it’s focused on long-term endpoints like survival and outcomes, which not only require large, lengthy, and expensive clinical trials, but also are wrought with uncontrolled variables that mask benefits in the aggregate and, especially, in individual patients.

The reason that the FDA requires this for diseases that affect large populations of patients is because it is frightened of ridicule from the public and Congress when approved drugs are shown to have side effects. So, by only approving drugs that have been shown to demonstrate great benefit after lengthy and expensive trials, the FDA mitigates potential criticism.

In order increase medical innovation, criticism of the FDA must stop. It will take a new cCommissioner who can articulate this forcefully and defend the agency’s decisions to change course.

In order to re-focus the FDA on safety and effectiveness, we have proposed tiered orders of approval based on one of four categories of clinical evidence – (1) biomarkers; (2) clinical signs and symptoms; (3) disease modification; or (4) long-term outcomes. This would provide drug developers with clear paths forward and encourage the development of innovative products for all diseases. It will also encourage investment by reducing regulatory uncertainty and development cost. And, it will lead to lower drug prices. 

With the absence of a new FDA chief as President Trump begins his Administration, will he conclude the same thing as John Jenkins, the retiring Director of the Office of New Drugs in FDA’s Center for Drug Evaluation and Research?— “CDER reviewed and approved 22 novel drugs, most of which have the potential to add significant clinical value to the care of thousands of patients with serious and life-threatening diseases.”

I don’t think so. Rather, I think he will ask, “What is the FDA doing to expedite development of drugs that have the potential to benefit millions upon millions of Americans?”

Joseph V. Gulfo is the executive director of the Lewis Center for Healthcare Innovation and Technology at Fairleigh Dickinson University and author of "Innovation Breakdown: How the FDA and Wall Street Cripple Medical Advances" (Post Hill Press). He has more than 25 years of experience in the biopharmaceutical and medical-device industries and is the former CEO of Mela Sciences. Follow him on Twitter @josephgulfo.


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