Thousands Claim A Blockbuster Drug Gave Them Cancer

cancer from one of the world's most popular drugs. In November, we talked about how a small independent lab in Connecticut called vallish Or discovered in that samples of Zantac, the widely used heartburn pill, contained the possible carcinogen n d m A. At first, the company that made the drug at the time it was called Glaxo and now it goes by g s K they pushed back against the lab's findings, and so did the US Food and Drug Administration,

But in the FDA pulled Zantac from the market. The agency also requested that all pros ryption and over the counter drugs containing renittedine, which was the active ingredient in Santech, be removed from store shelves. A new version of Zantech is back on the market. It's been reformulated and it's no longer made with renittedine. It's considered safe to use as directed. But now tens of thousands of people who

took the old version of the drug have sued. They claim it gave them cancer, and the alleged the company was made aware of potential problems with the drug but didn't act quickly enough. My colleagues Anna Edney, Susan Burfield, and Jeff Feely dug deep into the claims and counterclaims in these lawsuits for Bloomberg Business Week. They're here to explain what's at stake and just how complicated it is to try to prove a drug made someone sick. Susan, can you tell us about Zantec and why it was

such a big deal. Zantac was first developed to treat ulcers at then got approved to treat heartburn, and along the way became a billion dollar drug for Glaxo and the best selling prescription of all time. So hugely important to the company that developed it, pretty important for a lot of people, millions of people who were taking it, and now, of course, you know, important for people to understand what happened during all those years between development and now.

And one of the reasons this drug became so popular, Anna, as you're writing the story is that it was one of the first drugs that was marketed directly to consumers. That's right, Um, we see ads all the time now on TV. I think and we think of those and

and make fun of them from time to time. And you know, it wasn't as ubiquitous back then, but Blacks made sure that it had an enormous salesforce, combined forces with another company, um to try to to make sure that they were getting the word out about this drug, and even went too far sometimes and we're bromanded by the Food and Drug Administration for some of the claims

that they tried to make. And and all this time that this drug was selling in huge amounts of making this company a lot of money, there were indications behind the scenes that there were potential problems with it. Could you describe exactly what was the problem with this drug? Yes, Um. These indications that there was a problem with the drug started before was even approved by the Food and Drug Administration.

There was some testing that black so did internally that showed that under certain conditions Zantalk, which you know, before it was approved, was called nitadine because that's the active ingredient in it. This testing show that nittadine could form a probable carcinogen called n d m A. So how did that happen? Where did the n d m A come from? So what they found out with Zantok is that nittadine itself degrades to form n d m A, and this can happen over time while it sits on

the shelf. This also can happen in heat and humidity. So maybe when you're transporting the drug and you're the truck might be um have higher temperatures. When they're taking it to the drug store. This can be in your bathroom. You know, these are pretty normal temperatures where it's able to increase the amount of n d m A on the drugs, So you don't just have a set amount of n d m A, but it rises over time

and with heat. What they have argued is that it would have only been in conditions that just aren't even possible to happen within the human body, so that at the time the drug is manufactured it can be just fine, but over time, sitting in your medicine cabinet can develop this probable carcinogen all by itself. That's right. The n

d m A is formed when the drug degrades. The drug has some characteristics that make it susceptible to forming n d m A. What happened is Glaxo looked into this once the news was out there in twenty nineteen, and they determined that they don't know exactly what is making it degrade. They don't think there's any sort of regular chemistry process that they can understand of how it

gets there. Probably one of the simplest ways to think about this is just that renitadine as a molecule is unstable, and so over time, in heat, in humidity, it degrades and that creates problems that we're seeing now. And why is and d m A a carcinogy and what does it do? And d m A was once used in rocket fuel but essentially, you know, it's not even allowed to be used in any commercial uses anymore. Essentially is only used now to cause cancer in um like lab rats,

animals that are being used for research. And they call it a probable carcinogen because it's never been tested on humans. But every single animal that has ever been given in d m A, no matter the species, has developed cancer. And it's not just a cancer, it's a laundry list

of cancers, bladder, lung, all sorts of different cancers. Jeff, how is it that you know everything that you're describing here the deliberations behind the scenes in the company, how they responded to various signs that they may have been something wrong. Well, we have access to the actual lawsuits themselves the complainants. We have access to the pre trial

depositions done of the Glaxo officials. We have access to internal documents that were turned over in discovery in some of the lawsuits, so you know, we got a pre wide view of what was going on. We also filed a freedom of information request with the f d A, so we also have the minutes of the meeting where a group of outside advisors and f DAS staff we're

talking with Glaxo scientists. At the end of the day, they suggested that the FDA go ahead and approve the drug Susan, What did G s K say when you presented them with what you found in your reporting about Zantac. We sent G s K a pretty detailed memo UM laying out what we had found, what we had seen in the court documents, what our own reporting showed. UM.

They declined to answer any of our specific questions. They did give us a statement that said that there is no scientific consensus about any consistent or reliable evidence that zantac increases the risk for any type of cancer. So basically they're saying the science is on their side. They also said that they will defend themselves vigorously against all claims in any litigation. What is the f d A say about approving written nity which they eventually then had

to pull from the market. Yeah, so the f d A gave us a statement that I'll just summarize. Basically, what they said is that they evaluate drugs according to the quote science of the day, and when there's a problem, they'll act quickly to figure out what to do. So I guess you know what they're saying is they did the best they could. And you write that GSK continues to say that renitted being does not cause cancer. Correct the way g s K is put it is that

there are no consistent signals that zantac causes cancer. What they mean by that is that there are conflicting studies. You know, nobody has given zantac to humans and said let's find out if this causes cancer. You can't do that ethically, but people have looked back in different epidemiological databases and things and tried to figure out if people

who took santac how to hire risk of cancer. It's true there's no consistent signal that it causes cancer, but there's also no consistent signal that it doesn't cause cancer. And uh, the last time you were on the show, you were telling us about the small lab called Valisher and it saw a problem with renitaine. Can you just remind us what they found? Yeah, vlisher at the time, so this was in twenty nineteen. They are an independent lab.

At the time, they were also a pharmacy and so they were testing all the drugs that came through and so they happened to be testing some zan talk, some renitodine and they saw these super high levels of n d m A. They took that information, they ran more tests. They kept finding d m A and every single bat that they tested, and so they wrote up that information and they sent it to the Food and Drug Administration as a petition saying you need to look into this, Jeff.

We should say that the concerns we're talking about here are no longer a problem with the current version of zante that's on sale now. Is that right? Zan Hack did come back on the market, but randditine was taken out of it as the active ingredient, and they replaced it with another one. So you can get zantac today, but it will not have Rand did a team in it. After the break, the lawsuits over Zantac get under way, Jeff.

Has been a few years since the old version of Zantac that was made with nitadine was pulled from the market. Now a lot of people who took that version of the drug claimed they got cancer and they're suing. Can you walk us through what's happening. Sure, So there are two sets of cases. At last, we have in this country, two separate places where you can sue in federal court. They were roughly about fifty cases filed and they were

all consolidated before a judge in Florida. That judge re sently found that the science underlying the claims was flawed and throw those cases out. The plainiffs, the people lawyers for those who took the antach or appealing that decision. So fifty people who claimed they were sick sued, their cases were put together and they were just thrown out. That seems like a fairly sweeping judgment to happen. Early on in the case that must have been a little controversial.

It was and it is. These cases were brought together and what's called a multidistrict litigation and MDL, and it's where you have a legal issue that gets filed in different federal courts around the country. They are consolidated before one judge for pre trial information exchanges and test trials.

One of the pre trial things that are done in all these cases is sort of a check on the science that underlies them, and they have a hearing and the planeffs put forth their experts and they testify how they came to the inclusions that randiditine was possible carcinogen. So it's up to the judge to decide if that

science is legitimate enough in the cases can progress. This judge in Florida decided that the science was flawed, that it was not independent enough, it was tied too closely to the litigation to be considered, you know, legitimate independent research, despite the fact that these tests that Valisher and others had done showed this probably link and that the FDA

itself ordered the drug pulled from the market. Correct And she even noted in her in her decision the irony of throwing these cases out when you have a recalled drug, but she found that the science just did not stand up as far as she's concerned. Now, this is one federal judge and her decisions are appealed to annals and groups of federal judges who review them. So we'll see what the outcome of that is yet. And in that statement that g s K gave us UM in response

to our questions, they talked about that ruling um. They noted that it was forty one pages that the judge had reviewed thirteen studies and had concluded, as they do, that there's no scientific consensus about nitadine and its linked to cancer. So this ruling was really great news for g SK and they, you know, continue to like to refer to it because they feel and hope that it

should be the last word. Did the f d A weigh in on this suit, they've you know, said pretty much the same, there's no consistent signal that zantac causes cancer. And even since the f d I put that statement out, which was originally in June, there's been more studies, more inconsistent evidence that it causes cancer or it doesn't. It just goes both ways. They can't really take a position

on this. It's it's not clear. I mean, there's no It's not like asbestos, where there's a consensus that you know, asbestos is a carcinogen. You know, there's just not a consensus yet. But the FDA ordered randentitying off the market just to make sure. I mean, you can't if there is a possibility that this stuff is causing cancer, you don't want it widely distributed. Jeff, you described that when federal Casey you said there is another bachelor cases going.

There's been seventy thousand cases filed. Most of them now are in Delaware State Court in Delaware, that is because that's where all of these companies US operations are incorporated. The deal with these is that the states have a different standard for judging the legitimacy of science then the federal courts, and so it's more likely that more of these cases are going to make it to trial that the judge in Delaware. And cases are also fount in California, Pennsylvania.

And these are all individual, they haven't been all put together. That is correct, as they're all again all individual personal injury cases. That's right, Jeff, What are all of these tens of thousands of plaintiffs asking for First of all, all civil lawsuits are about money, so they're asking for damages for their injuries. They want to be reimbursed for their medical costs, for the pain and suffering of the

cancer treatments. You know, God forbid. The person who took antack has died, his family wants compensation for the loss of that person, loss of his income. So it's always about money, Susan, Even if a drug is thought to be a possible carcin engine, it's still very difficult, I imagine for any individual person to claim that he or she got cancer from that drug, as cancer can come from a lot of different things. Yeah, that's exactly right.

I mean, for all of these cases, and in almost every kind of cancer I think, except you know, as Jeff said, asbestos tobacco. You know, the cancer develops years after you've either been exposed or have been ingesting something that's harmful, and to be able to make that connection can be complicated. And that's I think what the f d A statement is suggesting. You know, about consistent signals, and you can say, as Anna did, there's not signals

that it always does, but there's not signals that it doesn't. Jeff, you're writing this story that in other similar pharmaceutical cases, the companies have often settled rather than risk having so many suits that could wind up with judgments against them. Do you think it's likely that the company is going to want to settle these cases rather than bring them all to trial. I think there's a strong possibility that

there will be a settlement at some point. It takes a while for these things to move into that posture. The companies and the planiffs want to test the strengths of their claims, and so they have test trials, they have early trials. After you have a number of these things, and some test trial periods last for twenty cases, others for five cases, then the parties come together and try to come up with some sort of reasonable accommodation that

is acceptable to both sides. And it's always about the money. And as someone who covers the pharmaceutical companies all the time and knows them, well, what are you looking for in these cases? What do you think is the most relevant thing that we should all be taking away from this? The Food and Drug Administration? What about our regulatory body that's supposed to be protecting us from dangerous drugs. They don't have a lot of resources to look into whether

it's that's still on the market is safe. I think that that leaves things up to the courts to decide. It leaves it up to juries to be the last line of defense for anyone who may have been harmed by a pharmaceutical product. And what I'm looking for here is I'm curious to see, you know, if these should get to a jury trial, how regular Americans feel about that? And Ednie Susan Burfield, Jeff Feely, thanks for joining me today. Thank you, thanks so much. No problem when we come back.

How drugmakers can spot potential hazards in their products. What should companies do then to ensure their products are safe both of the time they're made and after they've sat for months or years in your medicine chest. Dr yap Venoma can answer that question. He's the chief science officer at u S Pharmacopia, and he's extensively studied the dangers

of probable carcinogens called nitrosamines. One of those nitros means is and d m A, which we've been talking about today and is at the center of the legal dispute over the old version of zantac. He joins me to explain how his organization is setting standards to protect against the spread of nitros means and drugs. Yeah, can you

tell us first, what does US Pharmacopia do. Yes, the US Pharmacopeia is an organization that is about two years old, and our mission is to improve global health and we do this primarily by setting standards for medicines, for biologics, dietary supplements, food ingredients, and healthcare and related programs. And yeah,

can you explain exactly what are nitrosymedes. So nitros means are naturally occurring compounds that are present are ubiquitous in around US, in drug compounds, also in food and other areas. So that's why they're important. And you say they're in nature, where are they just naturally found? So nitrosmis can be formed by a variety of chemical processes. I won't go into the detail, but nitrosmin chemistry is in principle very straightforward and can be formed through a variety of processes

by chemicals reacting. They can form naturally, They conformed during chemical synthesis, they can form during certain degredation processes, and the reason we're talking about them is because they are also possible carcinogens. Yes, so they have been shown to be muta genic, so they can cause mutations in your DNA, and they are listed as probable or likely carcinogens in mammals including humans. Nitrosamins have been found in quite a few of the most widely used pharmaceuticals, drugs that a

lot of us are familiar with. Can you talk a little bit about which drugs that they've been found in and what's happened since that discovery. So it started with the discovery of nitros means in falseharten, which is a class of products that are used to treat blood pressure, so very widely used, and that led to recalls and investigations into the cause of the presence of nitroso means. That's what started this about three and a half years ago.

Since then, nitros means have also been found in other very widely used drugs, including drugs to treat diabetes, tuberculosis, infection, as well as gastric acids. So it's been found in a number of drugs that are used many, many times by people all over the world, including the United States. Now, how are these nitros means introduced into drugs, because clearly manufacturers don't want them there. How do they get into drugs?

So that's actually one of the concerns. So they are and it's now being established that they can be introduced into drugs by a variety of reasons. One is through the chemical synthesis route that is used to produce the drugs to make them. It's also been shown that through degradation, in the case of renitatin, which is the anti gastric acid medicine, that through degradation and by reacting with itself,

nitros means can be formed. A third way that it's been shown to be introduced through interaction with the drug itself, with the packaging and what we call excipients, which are substances used to stabilize and manufacture the medicine. So it's been shown to occur in drugs through a variety of methods. And because of the widespread sort of exposure to the public of what happened with renititin, there's more attention being

paid to nitros means. What are pharmaceutical companies doing, What is your organization US Parmacopia doing to try to stop the spread of nitrous means in pharmaceuticals. Yeah, there's a lot going on. First, maybe it's good to to mention that the very fact that these are being found and discovered and monitored, while of course reasons for concern, it's also a sign that the system is working because we need to know what's going on. So that I think

that's the first thing i'd like to say. So, since a couple of years, there's a widespread collaboration between the regulatory authorities who are responsible for the safety and the quality of medicine, the manufacturers, and other science organizations, including the u S Pharmacopeia to try and figure out how we can mitigate and how we can reduce and remove the presence of nitrose means in drugs. So there are

three things going on. First is we have to understand which drugs are at risk of forming or containing nitrose means. That's the very first thing. The sect and piece is we need a better understanding of how mutagenic or carcinogenic these are. They're not all carcinogenic, they're not all mutigenic, so it's very important to have more information as to

what they do. And then the third piece, very importantly, is to discover and to develop methods to actually detect them, and to detect them in a way that detect them very low quantities to make sure that we have a good handle on their presence. So these are the three buckets that we're all collaborating on. I would say us B is primarily involved in developing the methods and the standards that are necessary to analyze and to discover all

of these different nitroso means. USP participated in a study that found potentially forty one percent of active ingredients in pharmaceuticals could have nitros means in them. How concerns should we be that nitrous means and other potential carcinogens are in the drugs that we take. So do not be concerned to the point that you should consider stop using drugs because of this, because that's very important. That's always the guidance before making any decision. Talk to your doctor

and make the right decision. That's also in line with what regulatory authorities are saying. So this is a theoretical assessment of looking at all the different chemical structures of the drugs on the market and looking for the potential that with the emphasis on potential to develop them. There are a lot of other factors that go into whether or not the actually will form chemical conditions, storage conditions, temperatures,

all of these things are are important. So I don't want any of you to be alarmed by, oh, two out of five drugs are now do contain nitros means that is not the case. It is part of the network of the fabric that we are contributing to really help advance the science and knowledge about these compounds. That's what it is. One thing I'm really excited about and I'd like to share is the nitrosman Exchange that we

set up about two years ago. So that was literally an online community where scientists, regulators, healthcare professional come together to discuss and find potential solutions. And in fact, the article that you refer to that we discussed was actually a direct result of that. So we're proud that we are adding our contribution. We of course do not have the silver bullet. Nobody has the silver bullet, but it's very important that all of us contribute to this and

that's what we're proud of to do. In addition to the work that we're doing on providing physical standards and methods to allow many factors and regulators to actually test or these compounds in a validated and regulated way. Yeah, Venima, thanks for speaking with me today. Thank you, Thanks for the opportunity. You can read more reporting from Um and Edne, Susan Burfield and Jeff Feely at Bloomberg dot com. Thanks for listening to us here at The Big Take. It's

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