Zantac Lawsuit

Researching drug company and regulatory malfeasance for over 16 years
Humanist, humorist

Friday, April 19, 2013

Paxil Birth Defects... (They Knew)

Today I am going to revisit a Paxil birth defect case from 2009.

What makes this case unique is that court documents were made available, giving us all an insight into how trial lawyers operate and how unsealed evidence proved to be the downfall of British pharmaceutical giant, GlaxoSmithKline.

I'm going to focus on the opening statements that were read to the jury by the plaintiffs attorney. The purpose of an opening statement is for an attorney to tell a jury what he/she expects the evidence to show.

The case, LYAM KILKER, a Minor, by MICHELLE M. DAVID, as Next Friend and Individually VS. SMITHKLINE BEECHAM CORPORATION d/b/a  GLAXOSMITHKLINE, astounded many as little by little the truth came to the surface regarding Paxil's propensity to cause birth defects.

Lyam Kilker was born with heart defects. His mother, Michelle David, had taken Paxil during her pregnancy.

September 15, 2009
13 Courtroom 253, City Hall
Philadelphia, Pennsylvania

Sean Tracey of the Tracey Law Firm [Attorney for Kilker]
Glaxo were represented, as usual, by King & Spalding

To set the scene, in other words, to make this more humane than (as it turned out through the verdict) inhumane. Sean Tracey introduces both Lyam and his mom to members of the jury.

MR. TRACEY: May it please the Court, good morning.
JURORS: Good morning.
MR. TRACEY: I am going to reintroduce myself. My name is Sean Tracey. I represent Michelle David and Lyam Kilker. Before I begin, I want to reintroduce to you Jamie Sheller here, and there are a couple young lawyers up front here. Scott Love and Adam Peavy you are going to see wandering around and probably hearing from during this trial. Who you haven't met are my clients. This is Michelle David. Michelle, will you stand up. This is Michelle David. Over here with Michelle's mother is Lyam Kilker. Lyam is here with his grandmother. Lyam is going to stay a few minutes, then I think his grandmother is going to take him out of the courtroom.

 Next we see Tracey explain to the jury the injuries caused to Lyam Kilker.

MR. TRACEY: This is the time for me to talk to you about what I believe the facts are going to be, what I think the evidence that comes in during this trial is going to be through the witness stand starting this afternoon, and through the documents that I have obtained as a result of this lawsuit. And so I want to start that by, this is the name of the case, as you have heard, Kilker versus GlaxoSmithKline. And Lyam Kilker, this is going to be undisputed, Lyam Kilker was born October 24, 2005. And shortly after he was born, Michelle found out he had been born with a series of congenital heart defects. During the time Michelle was pregnant, before she was pregnant, she was taking Paxil. She was on Paxil for her first trimester. Now, Lyam, after he was born, was at the hospital and he was diagnosed and his heart defects, there really are three. One is called the ventricular septal defect. One is called an atrial septal defect. Those are holes on the inside of the heart in the walls that separate the four chambers of the heart. The other heart defect he had is something called an interrupted aortic arch. The aorta, where it is supposed to curve, doesn't fully develop. And so what he has is three different, distinct heart defects, each of them related to the failure of his heart to fully develop.

Tracey then goes on to explain to the jurors about the FDA pregnancy categories.

MR. TRACEY: The first one is pregnancy Category A. Are there adequate and well-controlled studies? Are there human studies that demonstrate there is no risk to the fetus? If it is Category A, you can take this drug with impunity and you don't have to worry about children, you don't have to worry about if she gets pregnant. You will learn during this trial that, I think, over 50 percent of pregnancies in the United States are unplanned. Women aren't planning on getting pregnant. That's why these categories can be so important. You don't just consider these categories when you have a woman who is planning a pregnancy. It is any woman of childbearing years who may become pregnant. The evidence in this case is going to be that GlaxoSmithKline knew that over 50 percent of the women in the United States became pregnant without trying to, they were unplanned pregnancies. They knew this back in the 1990s. So Category A, no problems.
Category B, we have done animal studies, doesn't look like there is any problems. Animal studies have failed to demonstrate a risk to the fetus, but we don't have any human studies.
Category C is, we have done animal studies, we have done animal studies, and the animal studies have shown an adverse effect on the fetus, but we don't have any human studies at all.
Category D is, there is positive evidence, there is positive evidence of human fetal risk based on a number of different things, either adverse reaction data from investigations they do or adverse marketing data from women and doctors reporting problems with the drug or from studies. And in that case in a Category D drug you do not prescribe that drug to women of childbearing age with one exception. If the doctor decides that the benefit to the patient is worth the risk to the fetus, then the drug can be prescribed. Doctor Healy, who is a psychiatrist and neuropyschopharmacologist who is going to testify this afternoon, will explain that there may be times when the disease is so serious that it may be worth the risk to the doctor and the patient if there is a life-threatening illness. If somebody is capable of harming themselves or others, they may make the decision to prescribe the drug if, there is no alternatives.
Category X is, we don't care what the benefits are. You do not give this drug to a woman unless she has a pregnancy test that shows she is not pregnant.

Tracey adds:

MR. TRACEY: In 2004 when Michelle David was prescribed this drug, it was a pregnancy Category C, and GlaxoSmithKline says their animal studies have revealed no evidence of teratogenic effects.
Tracey then explains to the jury the process of human development.

MR. TRACEY: In human development when women get pregnant, what you are going to learn and understand is that the most vulnerable time to the human fetus is from weeks 3 to weeks. That is when the fetus is dividing and growing and is the most susceptible to something called a teratogen to a drug that can cause a birth defect. During weeks 3 through 8 the body is rapidly, rapidly expanding, rapidly developing. Cells are being signalled to go to where they are supposed to go. The heart is developing by week 8. By week 8 the heart, from a cellular perspective, is almost completely developed, and there is nothing you can do after that to prevent the heart, to prevent a heart defect if it has already occurred. The importance of this is that when women don't know or aren't planning on becoming pregnant, many times, most of the time, by the time the woman finds out she is pregnant, the damage has been done. This is when in this time frame, weeks 3 to 8, almost every congenital abnormality -- that is a fancy word for a birth defect -- almost every congenital abnormality happens during this time frame.
Tracey goes on to explain to the jury what a teratogen is. In a nutshell, a teratogen is any agent or factor that induces or increases the incidence of abnormal prenatal development.

Enter Dr Sloot

MR. TRACEY:  So during the course of this trial you will hear about teratogens and teratogenicity and you will find out about whether Paxil is a teratogen. And one of the ways you are going to learn about this is through a study, an animal study, an animal study done by a doctor named Sloot. Doctor Sloot is a European doctor who works for another pharmaceutical company called Shearing Plough. Shearing Plough is a pretty big company. You may have heard of it. In May of this year, 2009, a study was published by Doctor Sloot. The study said this. What Doctor Sloot did is, he took Paxil and all the other reuptake inhibitors and he exposed rat fetuses to these 12 different drugs, including Paxil. And what Shearing Plough was trying to figure out, what they were trying to do was figure out whether one of the drugs that they were going to put on the market to compete with GSK's drug was capable of causing birth defects. And so they took the drug they were going to take to market, and before they took it to market, they did this test. And they compared it to all the other SSRIs. Because, as you will learn, GSK never did this test. What Doctor Sloot discovered in May of this year is that out of all the teratogen --out of all the SSRIs, the 12, only one was a clear teratogen, Paxil. He discovered that Paxil in May of this year was actually more powerful a teratogen than cocaine. It would be safer, according to Doctor Sloot's study, to take cocaine than it would be to take Paxil while you were pregnant.

The Evidence

MR. TRACEY: I told you earlier that the way you learn about this case is through evidence, through witnesses that take the stand, through documents. And you are going to see documents in this case that have never seen the light of day before. You will see internal GlaxoSmithKline documents that the FDA hasn't seen, that the United States Congress hasn't seen, and that no jury has ever laid their eyes on before. For the first time in this trial you will see these documents. They have been under seal for over three years. And that's the way, one of the ways, you are going to learn about what GSK knew and when they knew it.

Tracey then explains to the jury how Glaxo had purchased the compound [paroxetine] from a Danish company called Ferrosan. He continues...

MR. TRACEY: Ferrosan had done the preliminary animal studies to look at teratogenicity. And they were done, I believe, in 1979 and 1980. And one of the studies was called Study 295. This is a study where they give Paxil, paroxetine, to pregnant female rats. And what the evidence showed in Study 295 is that the rats that got no Paxil, 88 percent of them were alive or 12 percent were dead by the fourth day after they were born. The ones that were given 5 milligrams of Paxil, 65 percent were dead by day 4. The ones that were dosed with 15 milligrams of Paxil, 92 percent were dead by day 4. And in the ones that were given 50 milligrams of Paxil, 100 percent were dead by the fourth day after they were born.

Ferrosan's Dr Baldwin

MR. TRACEY: At the time a doctor by the name of Baldwin, who works for them, Doctor Baldwin looked at the studies. He looked at Study 295, another study called 296, another study called 297. And 12 years before they started selling this drug to women in the world, Doctor Baldwin had some comments about these studies. What he told them internally -- this is a document that nobody has ever seen before. What he told them internally was: There remains the possibility this compound could be teratogenic at higher dose levels. As he saw, as you just did, that the more Paxil you got, the more rats died. And these were not heavy doses of Paxil. What he was concerned about was whether or not Ferrosan or anybody else was going to conduct or intended to conduct peri and postnatal studies to answer the question to why the rats died. He wanted to know that. In 1980 he sent a memo to the powers-to-be at Beecham. He said this needs to be done. The rats died. He talked about embryolethality. That means the fetuses die.

FDA Revolving Door 

MR. TRACEY: Because I saw the animal studies that you just saw and the evidence that you will see about the animal studies and the rat pups dying, and I wondered how they could market the drug and say in the beginning that there were no problems with the drug. What I found out is that the FDA investigator that signed off and said you can sell your drug to the public is a guy named Gary Evanuic (sp.?). And Gary Evanuic, who signed off on Paxil being a Category B drug, now works for GSK. He works for GSK in the very department that sells Paxil.


MR. TRACEY: And as we are rocking along, in 1994 we are selling in the United States, we are selling in Europe. Business is brisk. Business is going well. And they want to move into other countries. They want to sell their drug in other countries. And they have a company called SmithKline or Smith Beecham Japan. It is one of their companies that is in Japan that sells their drug, one of their 70, I think, companies. And the Japanese, they suspected, were not going to accept their dead rat pup studies because they suspected the Japanese, because of the historical things that have gone on in Japan with birth defects related to Hiroshima, Nagasaki, and another environmental disaster there called Minamata, the Japanese had a heightened sense of concern. GSK believed that's what would be going on. And so GSK began discussions internally. Internally among themselves they said: What are we going to do, what are we going to do if Japan makes us do the studies to find out why the rat pups died? What are we going to do? Because what the documents, the internal documents that the FDA has never seen, that nobody else has ever seen, is, their conclusions were, if the Japanese make us do the studies to prove why the rat pups died, we might lose the United States market. So GSK was looking at science and research, not from the aspect of whether or not their drug was going to induce birth defects in children, but the evidence will be their only concern was commercial. Their only concern was whether they would lose the American market. The quote from them is: GSK concludes this is the study, the type of study we wish to avoid. We simply don't want to know the answer to these questions. They say: If the Japanese do request a study, if they do it, there is a potential problem, they may insist on us doing a study to their preferred design. And so what they did in March of 1994, they got a woman or man, I'm not sure which, I haven't been able to find out, named Gwyn Morgan. They got Gwyn Morgan involved. They put Gwyn Morgan in charge of reviewing the study designs that they would give to the Japanese. And Gwyn Morgan was to ensure for the company that any potential negative outcome from the studies is minimized. They designed the study to fail. They wanted the study to fail.

GSK Sales Reps

MR. TRACEY: GlaxoSmithKline has 110,000 employees. I think 40,000 of them are salespeople. What these people do, you will learn, is, they go to doctors' offices. And they take literature and they take cookies and they take lunch and they take pens and they take samples of Paxil. And they tell the doctors why they should prescribe their drug. These are bright, sophisticated, educated salespeople. They are the backbone of this company. And what they were telling doctors in the mid-1990s is that no drug is safer than ours for pregnant women.

Japan Revisited

MR. TRACEY: So we are rocking along. Remember that Japanese study I told you about, Doctor Patrick Wier? Well, they designed a study -- they avoided the studies they wanted to avoid and they designed a study that they thought would satisfy the Japanese, and they were right. But even in the study that was designed to fail, something cropped up, something that was potentially a problem for them. In this study done by GSK, which, quite frankly, by the way, was not a study designed to find out why the rat pups died, it was not a study designed to find out the answer to the questions Doctor Baldwin had in 1980, but some of rat pups did die, and they autopsied one of the rats. And in one of the rats they autopsied, they found that the rat that was found dead had edema, swelling around the heart, and it had a ventricular septal defect. The very same defect Lyam Kilker has. The very same defect that they had started receiving reports of in 1997. But they blew this off. They minimized it. In their conclusions they didn't even mention it. It is buried in the back of the study in an appendix.

Cannot Stop Taking Paxil

MR. TRACEY: Now, this case is primarily, primarily, about birth defects, primarily about what happened to Lyam Kilker and whether they knew about what would happen to him. But in the course of selling Paxil for the past 15 years other issues have come up. One of them is this. In the mid-1990s some studies came out, some literature came out, showing that Paxil had a significant problem with withdrawal. What that means is this. They were finding that women that took the drug and then want to the stop couldn't get off of it. So they would get sick. They would try to stop and they would get sick. And so they would be forced to keep taking the drug so they wouldn't be sick.

Glaxo Burying Data

MR. TRACEY: In the mid-1990s there had been some studies done, not by GSK but by others, and talking about withdrawal. This, you are going to learn from the evidence, caused them some concern. They were concerned about losing their market, losing their market to Prozac. And what they decided to do was, do their own study. And one of the documents you are going to see is this document, a document from a woman named Bonnie Rossello. Bonnie Rossello is the vice-president of GSK's marketing, Paxil marketing. And what Bonnie said in 1997 was: In response to this, let's do our own studies. Then we will own the data. If the results come back negative, we can bury it all. We can bury the evidence that our drug is a problem. In 1997 that's what she said.

The full opening statement can be downloaded HERE

After hearing evidence from both sides Jurors deliberated about seven hours over two days before finding Glaxo failed to properly warn doctors and pregnant users of Paxil’s risk. The panel awarded $2.5 million in compensatory damages to the family of Lyam Kilker.

The GlaxoSmithKline company tagline is, "Do more. Feel better. Live longer."

Bob Fiddaman


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