Cutting-edge science and the development of groundbreaking and lifesaving drugs get a lot of attention, but the everyday practice of medicine is often more mundane: It doesnt involve being CRISPRd or having gene therapy delivered into your cells. The truth is that most people who are very sick and visit their doctor get treated with very ordinary and sometimes very old drugs.

But in recent years supplies of some of these critical standby medicines have become disrupted. The shortages have forced doctors to make hard treatment decisions. Drugs have to be rationed or, in the worst cases, patients who need care can be turned away.

Dr. Ben Davies is a professor of urology at the University of Pittsburgh and a BioTwitter influencer (I dont think anyone has ever called me a BioTwitter influencer before, he says.). Davies recently chatted with STAT about the recurring problem of drug shortages.

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Youve had experience with shortages of a medicine called BCG. Whats the history of BCG and why is it so important for bladder cancer patients?

BCG is a very special and powerful antineoplastic drug. Its been around since the 1980s and Im sure you remember it being used for tuberculosis vaccination.

Its basically an attenuated microbacterium and it does three very powerful things. If you get bladder cancer thats non-muscle-invasive, it can prevent recurrences and it can stop progression of disease. That would be extremely helpful because bladder cancer can progress into your muscle, which requires a different form of treatment, like radical surgery. And it also can actually treat residual tumors that your doctor may not have seen on your initial look in your bladder. So its a very important drug. It has a great response rate of about 68%. Its very well-tolerated most of the time. I mean, its our first line of defense in treating non-muscle-invasive bladder cancer.

Why is BCG so vulnerable to shortages?

Because they make it in massive batches and if the batch goes bad, youre just basically done. And depending on how big the batches are, you could go for months making a big supply of it and then youre done if it gets contaminated. So its unlike making a pill where if you just notice a few bad pills you can throw them away and restart. This thing really makes you start again, like a few months later, and youre behind the eight ball.

Merck is the only company that makes BCG today. At one time Sanofi (SNY) was a supplier but it abandoned the drug in 2016. Are you surprised that a drug thats so widely used has only a single manufacturer?

Well, I would be surprised if I didnt know the economics behind it. The problem is that the barrier to entry is quite high and extremely expensive. You know, the Mylans of the world youd think would just jump into this market. But theres a huge barrier to get in there $100 million or more. That and the drug is relatively cheap. So youre not going to make much money if you jump in. Im not surprised there arent so many suppliers now. We need to change those things to make it a more sought-after and more manufactured drug.

Were saying: We dont have the drug thats going to help you and that its going to cost you more.

Dr. Ben Davies, University of Pittsburgh

I mean, I am surprised that Merck has done such a Im gonna use a urologic term piss-poor job of making it since 2016. So weve had a good almost three years of years of problems getting the drug just their problem basically of getting it to patients and I dont know why they havent done a more robust response to the need. I mean, its not like the actual amount of bladder cancer patients changes over time. Its pretty stable. They know how much they need. They just havent been able to do it.

As a physician, when you have a patient before you with bladder cancer, what do you do when BCG is in short supply or not in supply at all?

When its not in supply at all, we go to alternative drugs like mitomycin, which is much more expensive. I wrote a small paper in the New England Journal about how as soon as BCG is unavailable, the price of mitomycin spiked by four times. But we go to other drugs. If we dont have enough, we stop something called maintenance therapy in a lot of patients. Thats a time when you get the drug continually only to help stop recurrences and wed lower the doses. So therere a few things we can do, which seems to be OK. But its certainly not as efficacious as getting the whole drug.

If you had power or influence over the supply of BCG, what would you do to try to make the drug more plentiful?

Oh, God, I think the number one thing, and Ive said this publicly and Ive written about it, you have to think, unfortunately, even though Im a card-carrying liberal, you have to raise the price of the drug. If manufacturers arent going to make any money on the drug, theyre simply not going to be that interested in making it. And thats just the system we live in. So if we dont do that, then we can think about federal mandates, but that has not worked well in the history of drug problems and shortages. So in my view, you have to increase the price and find a willing manufacturer, unlike Merck, that is willing to make the drug correctly and in appropriate amounts.

BCG is not the only drug thats often in short supply. At any given time there can be dozens, sometimes hundreds, of older medicines that appear on the FDAs drug shortage list. Do you think this problem is getting enough attention?

I dont think its really in peoples wheelhouse because they dont see it. I mean, I see it every day.

Its really a horrific situation. When I sit down with the patient, I tell him I cant give you the drug. It has such a great response rate. Instead Im going to give you an inferior drug that has a poor response rate. And by the way, its four times as much money, which is an important consideration in many of the medical plans that have people pay considerable amounts of money out of pocket for their drugs. And thats basically what were saying: We dont have the drug thats going to help you and that its going to cost you more. So its a major problem.

Much of this issue is tied up in the economics of how drugs are bought and paid for in this country. Recently Jeremy Corbyn in the U.K. proposed starting a government-run generics manufacturing establishment over there and there was a similar plan that Elizabeth Warren had described in terms of getting the government involved. What do you think of that as an idea for an issue like BCG?

I think it would work for BCG. I mean, I kind of mentioned my political stripes so I dont mind government intervention when its necessary. We already have this program, by the way. The governments heavily involved right now in getting appropriate vaccinations to people and supports it with its own money. It doesnt have the manufacturing capabilities. I think we need some sort of federal mandate where that means they have the private sector contracted or something like that. And I think that I would be completely in support of that for issues like this.

Theres another company proposing to do this a little bit. Nothings actually happened, but a conglomerate of universities were all going to come together and make, like, saline and epinephrine and all these bizarre drugs that we dont have available. Civica Rx. It sounds like a great scheme, but nothings ever actually happened. Its been mostly talking.

I was talking to my good friend Amitabh Chandra from Harvard who is a health economist about this. He says that a lot of this, he thinks, could be solved by better distribution. In other words, right now if I have enough BCG in my hospital but the hospital across the street does not have any, theres no real easy mechanism for me to give them that BCG, even though I could. There is a massive sort of inter-hospital or between-physician lack of communication and resources to exchange drugs or therapies with ease. You can imagine theres a good reason for that, for regulatory reasons.

But there is an opportunity, I think, to increase abilities to hand off drugs to other people easier and that would obviously alleviate some of the problems.

A good example of that is we can commonly have doctors in the community who dont have any BCG at all for whatever reason and so then those patients will come to see me, often many hundreds of miles to get BCG because their doctor cant get any. Well, thats silly. Why cant I ship that BCG to that doctor? So I mean theres things like that which can be done which would ameliorate the situation. But the bottom line is that we have a failure of manufacture. We have a failure, really, of imagination on how to fix this problem. This has been going on since at least 2012. Just nothing has ever happened to fix it.

Let us know when you start the BCG socialist collective.

Want me to start one?

This is a lightly edited transcript from a recent episode of STATs biotech podcast, The Readout LOUD. Like it? Consider subscribing to hear every episode.

See the article here:
What one doctor thinks about drug shortages and how to solve them - STAT

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