Source: https://www.masstortnexus.com/mass-torts-news/category/zofran/
Timestamp: 2019-04-24 18:11:22+00:00

Document:
Plaintiff attorney Tobias L. Millrood of Pogust Braslow & Millrood LLC.
US District Judge F. Dennis Saylor IV shot down a defense motion and allowed fraud claims filed by 365 plaintiffs to proceed, charging that manufacturer GlaxoSmithKline (GSK) marketed Zofran to pregnant women, knowing it would cause birth defects.
The judge is overseeing litigation in In Re: Zofran (Ondansetron) Products Liability Litigation, MDL No. 2657 in the District of Massachusetts.
There are three categories of alleged misrepresentations in this case.
The first category consists of statements allegedly made by GSK in its advertising, marketing, and promotional materials—in other words, statements made generally to the marketplace.
The second category consists of specific statements made by GSK representatives to prescribing physicians, including statements made by sales representatives to physicians, or specific written materials provided to individual physicians.
The third category consists of statements made in Zofran’s product labeling.
The allegations are in either the master complaints or the individual short-form complaints. The plaintiffs are represented by Tobias L. Millrood of Pogust Braslow & Millrood LLC, Kimberly D. Barone Baden of Motley Rice LLC, M. Elizabeth Graham of Grant & Eisenhofer PA, and Robert K. Jenner of Janet Jenner & Suggs LLC and and Kimberly Dougherty of Andrus Wagstaff.
Zofran is an anti-emetic referred to as selective serotonin 5-HT3 receptor antagonists. Serotonin signaling in the body triggers nausea and vomiting. The active ingredient in Zofran, ondansetron, is believed to alleviate symptoms of nausea and vomiting by inhibiting the body’s serotonin signaling.
Serotonin signaling regulates developmental processes that are critical to normal embryonic development. Inhibiting serotonin signaling during embryonic development can therefore increase the risk of birth defects. According to the complaint, pre-clinical studies conducted by or on behalf of GSK in the 1980s revealed that Zofran ingested by mammals—in particular, rats and rabbits—during pregnancy crosses the placental barrier, exposing the fetus to the drug. The complaint alleges that subsequent scientific research has confirmed that Zofran also crosses the placental barrier during human pregnancies.
According to the complaint, animal studies conducted by or on behalf of GSK in the 1980s in Japan revealed clinical signs of toxicity, intrauterine fetal deaths, stillbirths, congenital heart defects, craniofacial defects, impairment of ossification (incomplete bone growth), and other malformations in fetuses exposed to Zofran during gestation. The complaint also alleges that from 1992 to the present, GSK has received reports—either directly or through studies published in medical literature—of birth defects in children exposed to Zofran or ondansetron during pregnancy.
Around 1997, GSK launched a marketing scheme to promote Zofran to obstetrics and gynecology healthcare practitioners and consumers as a safe and effective treatment for pregnancy-related nausea and vomiting.
According to the complaint, “[a]s a result of GSK’s fraudulent marketing campaign,” by 2002 Zofran had become the most frequently prescribed drug for treating pregnancy-related nausea and vomiting in the United States.
Pregnancy: Teratogenic Effects: Pregnancy Category B. Reproduction studies have been performed in pregnant rats and rabbits at I.V. doses of up to 4 mg/kg per day and have revealed no evidence of impaired fertility or harm to the fetus due to ondansetron. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Today, nearly 8 in 10 prescriptions filled in the US are for generic drugs, according to the FDA. The use of generic drugs is expected to grow over the next few years as a number of popular drugs come off patent.
But who is liable when a generic drug makes sells a bioequivalent drug to a patient who suffers a personal injury from taking it?
Two US Supreme Court cases insulate the generic makers from responsibility, so long as they included the branded drug maker’s warnings. But now courts in California, Vermont, and Illinois have accepted the notion of “innovator liability,” imposing liability on the branded drug maker for injuries caused by a generic drug equivalent.
Research shows that generics work just as well as brand-name drugs. A study evaluated the results of 38 published clinical trials that compared cardiovascular generic drugs to their brand name counterparts. There was no evidence that brand-name heart drugs worked any better than generic heart drugs. See JAMA. 2008;300(21)2514-2526.
The FDA says that any generic drug modeled after a single, brand name drug must perform about the same in the body as the brand-name drug. There will always be a slight, but not medically important, level of natural variability – just as there is for one batch of brand name drug compared to the next batch of brand name product.
California, Vermont, and Illinois state law rulings impose liability on the original drug company innovator for injuries caused by a generic drug equivalent.
Two notorious US Supreme Courts rulings have immunized generic drug makers from liability in product liability and failure to warn claims.
PLIVA, Inc. v. Mensing, 564 U.S. 604 (2011), holds that federal drug regulations applicable to generic drug manufacturers directly conflict with, and thus preempt, state-law tort claim alleging a failure to provide adequate warning labels.
Mutual Pharmaceutical Co. v. Bartlett, 570 US 2468 (2013), holds that generic drug manufacturers cannot be held liable under state law for not adequately labeling medication when federal law prohibits them from changing the label from the original brand name drug.
However, in California, Vermont, and Illinois, these rulings did not protect branded manufacturers from innovator liability claims, because the companies controlled the text of the warning labels.
Plaintiffs argue that the physicians “reasonably and foreseeably” relied on the representations of branded manufacturers when prescribing a generic drug, because physicians understood that generics are bioequivalent to and have the same labeling as branded drugs.
In the event that the branded manufacturer made misrepresentations or engaged in other unlawful activities such as “off-label” marketing, plaintiffs further argue that physicians relied on the branded manufacturers’ misrepresentations, understood that generics are bioequivalent to the branded product, and prescribed the generic based on the branded manufacturers misrepresentations.
Only California, Vermont, and Illinois state law rulings impose liability on the original drug company innovator for injuries caused by a generic drug equivalent.
Conte v. Wyeth, 168 Cal.App.4th 89, 85 Cal.Rptr.3d 299 (2008), involved a user of generic metoclopramide who brought an action against Wyeth, the manufacturer of Reglan, the name-brand form of metoclopramide, for fraud, fraud by concealment, and negligent misrepresentation.
The court of appeals held that Wyeth’s common-law duty to use due care in formulating its product warnings extends to patients whose doctors foreseeably rely on its product information when prescribing metoclopramide, whether the prescription is written for and/or filled with Reglan or its generic equivalent.
In T.H. v. Novartis Pharmaceuticals Corp., 199 Cal. Rptr.3d 768 (Cal. App. 2016), the court of appeals imposed innovator liability in perpetuity − for injuries occurring even after an innovator manufacturer had sold all rights and left the relevant market altogether.
Note: This decision is currently under appeal. If Novartis wins this appeal Conte would not be overturned, innovator liability would simply end at the point (if) the brand manufacturer discontinued the marketing of the brand drug.
Vermont chose to recognize innovator liability in Kellogg v. Wyeth, 762 F. Supp.2d 694 (D. Vt. 2010). The plaintiff filed suit against the brand name and generic manufacturers of metoclopramide for strict product liability, breach of express and implied warranties, negligent misrepresentation, fraud and fraud by concealment.
A federal court interpreted state law, imposing a duty on Wyeth because it was “fair” to do so, and there is no reason, under Vermont law, to limit defendant’s duty of care to physicians by the pharmacist’s choice of a generic bioequivalent.
Dolin v. SmithKlineBeecham Corp., 62 F. Supp.3d 705, was a wrongful death action against SmithKline Beecham Corporation involving a man who committed suicide after taking paroxetine, the generic version of Paxil.
A federal court interpreted Illinois law to impose a duty of reasonable conduct upon GSK. The plaintiff’s common law negligence and negligent misrepresentation claims survived summary judgment.
Note: Under Illinois law a product liability claim under an innovator liability theory would likely fail where as a negligence claim would survive.
In an unusual move, Judge Dennis Sailor presiding over MDL 2657, has approved two master complaints, one for branded drug use and a separate Master Complaint for plaintiffs that wish to pursue GSK under innovator liability theories.
Judge Sailor is overseeing 364 lawsuits in MDL 2657 in federal court in Massachusetts, IN RE: Zofran (Ondansetron) Products Liability Litigation.
101. Defendants knew or should have known that consumers such as Plaintiffs would foreseeably use the generic bioequivalent of Zofran and rely upon representations and omissions of Defendants as the holders of the NDA for Zofran.
Although the Master Complaint does not contain language that limits its use to claims governed by the laws of the three “innovator liability states,” the defense is free to argue these claims based on the laws of the state of original jurisdiction. For states that do not have settled caselaw related to innovator liability, it is likely that the defense will prevail in most cases.
Mensing and Bartlett both turned on an “impossibility preemption argument,” in that is not possible for a generic manufacturer to legally alter the warning label. The generic label most conform exactly to brand label.
What if the brand drug manufacturer also makes a generic version of its own drug? Obviously, the brand manufacturer would control both the brand label as well as the generic label under this circumstance and the impossibility preemption reasoning of Mensing and Bartlett would not apply.
Novartis purchased GlaxoSmithKline’s oncology division in March of 2015. Along with Glaxo’s cancer business came the right to sell Zofran. Novartis also owns Sandoz, which manufacturers a generic version of Zofran. Therefore there is a strong argument that Mensing and Bartlett do not provide protection for Zofran Generics made by Sandoz after May 2015.
US District Judge F. Dennis Saylor organized discovery into five phases on Nov. 10 In Re: Zofran (Ondansetron) Products Liability Litigation, MDL No. 2657 in the District of Massachusetts.
About 300 lawsuits have been filed against GlaxoSmithKline LLC, based in Wilmington, DE, since the MDL was formed by the Judicial Panel on Multidistrict Litigation on Oct. 13, 2015.
Phase 1 — Product identification fact sheets, plaintiff fact sheets and defendant fact sheets must be released as required by MDL orders 10, 11 and 12 dated May 26, 2016.
Phase 2 — Electronically stored information relating to whether Zofran causes birth defects and injuries alleged, and all potential preemption issues must be released. Phase 2 is likely to require expert and fact discovery.
Phase 3 — Beginning immediately, this phase will cover general causation issues and whether any FDA approval or other action preempts any of theplaintiff’s claims.
Phase 4 — To star on Feb. 1, 2017 will consist of discovery concerning individual causation, product identification or damages.
Phase 5 — Beginning at a date to be determined, this phase will covery any remaining potentialy relevant issues.
Defendant GlaxoSmithKline LLC d/b/a GlaxoSmithKline GSK knew as early as 1992 that Zofran passed through the placenta and into a developing fetus and presented “unreasonable risk of harm” to developing babies.
GSK marketed Zofran “off-label” for treatment of nausea and vomiting associated with pregnancy. The company represented that Zofran was a safe and effective treatment for the nausea and vomiting associated with pregnancy. However, the drug had not been studied for its adverse affects upon pregnant mothers, or the possible teratogenic effects upon their fetuses at any time between 1991 and 2011.
Between April 2009 and December 2013, GSK reported that it made paid doctors and healthcare institutions more than $437.9 million dollars in the United States for speaking fees, consulting fees, research, travel fees and meals.
The adoption of the Short Form Complaint is, in effect, the filing of an amended complaint, for which no additional fee is required. However, any plaintiff who files a new case directly in this MDL proceeding must pay the required filing fee. In other words, the filing of a new action requires the payment of filing fee, but such a fee need only be paid once.
Federal Judge F. Dennis Saylor IV on July 8, 2016 approved the new Short-Form Complaint and Jury Demand submitted by the parties in Zofran (Ondansetron) Products Liability Litigation.
In 2013, GSK made $12.8 billion in sales in the United States, making it the fifth most lucrative pharmaceutical company doing business in the United States according to IMS Health.
Judge Saylor is hearing 260 Zofran Cases Filed Against GlaxoSmithKline in federal court in Massachusetts.
That since 1992, the company has received hundreds of reports of children who were born with serious abnormalities following pre-natal exposure to the drug.
That as early as 2006, studies have suggested that Zofran crosses the placental barrier in significant amounts when taken by pregnant women, which may potentially harm a developing fetus.
That Zofran has never been approved to treat pregnancy-related nausea and vomiting, and accuse Glaxo of improperly marketing the medication for this purpose.
In 2012, the drug maker agreed to pay $3 billion to resolve illegal marketing charges with the U.S. Department of Justice that involved a number of its medications. Among other things, the company had been accused of illegally promoting Zofran as an off-label treatment for morning sickness.
In contrast, GSK knew that Zofran was unsafe for ingestion by expectant mothers. In the 1980s, GSK conducted animal studies which revealed evidence of toxicity, intrauterine deaths and malformities in offspring, and further showed that Zofran’s active ingredient transferred through the placental barrier of pregnant mammals to fetuses. A later study conducted in humans confirmed that ingested Zofran readily crossed the human placenta and exposed fetuses in substantial concentrations. GSK did not disclose this information to pregnant women or their physicians.
US District Judge F. Dennis Saylor IV on July 8, 2016 approved the new Short-Form Complaint and Jury Demand submitted by the parties in Zofran (Ondansetron) Products Liability Litigation.
Master Short-Form Complaint and Jury Demand—Generic Ondansetron Use, Docket No. 274, Exhibit B, filed June 20, 2016.
This Order will trigger certain requirements under MDL Order No. 14, including the requirement that each current plaintiff file a Short-Form Complaint within 30 days of this Order.
When pregnant women take Zofran, it leads to birth defects. Novartis has been aware of this since before it began selling Zofran.
In an important new development, the federal court in Massachusetts where Zofran birth defects lawsuits are docketed, has added Novartis Pharmaceuticals Corporation as a defendant. More than 260 cases are pending against Novartis and GlaxoSmithKline.
The lawsuits are consolidated before Judge Dennis Saylor in MDL2657, Zofran (Ondansetron) Products Liability Litigation.
Effective March 23, 2015, Novartis AG, a Switzerland company, acquired GlaxoSmithKline PLC’s oncology business, including the right to sell Zofran products in the US. On March 23, 2015, Novartis Pharmaceuticals Corporation, a US corporation and subsidiary of Novartis AG, became the NDA holder for Zofran. On March 23, 2015, Novartis assumed responsibility for maintaining the content of Zofran’s labeling in the US, including warnings and precautions attendant to its use.
Until GSK’s sale of its Zofran business to Novartis, GSK designed, manufactured, marketed and, sold Zofran. After the sale, GSK continued to manufacture Zofran for sale in the US by Novartis, and it became involved in the research, manufacture, testing, packaging, labeling, advertising, promoting, marketing, and selling of Zofran in the United States.
Novartis is a Delaware corporation headquartered in East Hanover, NJ and it conducted business throughout the US. The company has derived substantial revenue from pharmaceutical sales throughout the US, including Zofran.
In connection with its acquisition of Zofran from GSK, Novartis gained knowledge of the false and misleading promotion of Zofran for treating pregnancy-related nausea, sometimes called morning sickness, and of the risks of prenatal exposure to Zofran. Novartis had a duty and continues to have a duty to warn adequately and to correct GSK’s misrepresentations and has failed to do so.
Zofran is a prescription drug indicated only for preventing chemotherapy-induced nausea and vomiting, radiation therapy-induced nausea and vomiting, or post-operative nausea and vomiting. Drugs that prevent or treat such nausea and vomiting are called anti-emetics. Zofran is part of a class of anti-emetics referred to as selective serotonin 5-HT3 receptor antagonists.
Disruption of signaling pathways through neurotransmitters other than serotonin.
Defendants have been aware of these facts at all relevant times, but they have failed to tell healthcare providers, their patients, or the public of the impact of these potentially life-threatening conditions on the developing embryo and fetus.
In 1991, Zofran became the first 5-HT3 receptor antagonist approved for marketing in the US. Defendants have never applied for FDA approval of Zofran for treating pregnancy-related nausea or vomiting. Neither the safety nor efficacy of Zofran for treating pregnancy-related nausea or vomiting has been established.
With more than 6 million annual pregnancies in the US since 1991 and an estimated 70-85% incidence of pregnancy-related nausea, GSK had an extremely lucrative business opportunity to create a new market for Zofran. GSK seized that opportunity, but the effect of its conduct was tantamount to experimenting with the lives of unsuspecting mothers-to-be and their children throughout the US.
As early as January 1997, despite available evidence showing that Zofran presented an unreasonable risk of harm to babies exposed to Zofran prenatally, GSK launched a marketing scheme to promote Zofran to obstetrics and gynecology healthcare practitioners and consumers as a safe and effective treatment for pregnancy-related nausea and vomiting. In support of its misleading marketing efforts, at least as early as January 1997, GSK offered and paid substantial pay to healthcare providers and “thought leaders” to induce them to promote and prescribe Zofran to treat morning sickness.
GSK’s Zofran sales representatives received incentive-based compensation that included an annual salary and a quarterly bonus. The bonus amount was determined by each sales representative’s performance in the relevant market and whether the representative attained or exceeded quarterly sales quotas. The more Zofran sold by a GSK sales representative or prescribed by a provider in that representative’s sales territory, the greater the compensation and incentives.
As a result of GSK’s fraudulent marketing campaign, the precise details of which are uniquely within the control of GSK, Zofran achieved blockbuster status by 2002 and became the most frequently prescribed drug for treating morning sickness in the United States. In 2002, sales of Zofran in the United States reportedly totaled $1.1 billion.
GSK’s promotion of Zofran for use in pregnancy eventually led to a federal governmental investigation. On July 2, 2012 the U.S. Department of Justice announced that GSK “[a]greed to plead guilty and pay $3 billion to resolve its criminal and civil liability arising from the company’s unlawful promotion of certain prescription drugs,” which included Zofran, among numerous others.
Part of GSK’s civil liability to the government included payments arising from claims that GSK: (a) promoted and disseminated false representations about the safety and efficacy of Zofran concerning pregnancy-related nausea; and (b) paid and offered to pay illegal remuneration to healthcare professionals to induce them to promote and prescribe Zofran for this purpose.
Since before Zofran entered the U.S. market, GSK has known that serotonin also regulates developmental processes that are critical to proper embryonic development. Impeding serotonin signaling during embryonic development can increase the risk of developmental insult. GSK has likewise known that, when Zofran is taken, its established side effects in adults can also occur in embryos and fetuses, leading to birth defects. Novartis has been aware of these facts since before it began selling Zofran.
Federal law enforcement agencies announced a $54 million settlement against Salix Pharmaceuticals for using “speaker programs” to pay kickbacks to doctors so they would prescribe company drugs and medical devices.
Announcing the settlement were the US Attorney for the Southern District of New York, the U.S. Department of Health and Human Services, the Office of Inspector General’s New York Region, and the FBI.
Salix held sham speaker programs, often at high-end restaurants (such as Nobu and Le Bernardin in New York City), with per-person costs exceeding $300. The doctors got substantial speaker fees at fake continuing medical education (CME) programs and spent little or no time discussing the product.
Under the settlement, Salix must pay about $46.53 million to the federal government plus $7.47 million to resolve the state law civil fraud claims.
“Salix found a way to pay doctors money and treated them to fancy meals to push their drugs. With today’s settlement, Salix has taken responsibility for its conduct and agreed to pay a significant financial penalty. This is part of our continuing effort to pursue health care providers who put their profits ahead of patient safety,” said Manhattan U.S. Attorney Preet Bharara.
Salix is a specialty pharmaceutical company based in Raleigh, North Carolina, that sells products used to treat various gastroenterology conditions. From January 2009 to December 2013, Salix’s speaker programs for Xifaxan, Apriso, Relistor, MoviPrep, OsmoPrep, Solesta, and Deflux were nothing more than social events where Salix wined and dined doctors to induce them to write prescriptions for these products.
At many of its speaker programs, Salix repeatedly invited the same doctors, who often were from the same practice or otherwise knew each other, to attend the same program on the same topic. In pre-recorded programs – which Salix staff called “doc-in-the-box programs” – the pre-recorded video often was not played or was intentionally played in a way so it could be ignored.
Many of these doctors increased their prescription-writing for Salix drugs after becoming speakers or repeatedly attending sham speaker programs. Salix spent about $25 million on speaker payments and meals.
The speaker programs were an important part of Salix’s strategy for increasing sales of its drugs. The company conducted about 10,000 speaker programs, including about 8,000 programs alone for Xifaxan, Apriso and Relistor.
Speaker honoraria payments ranged from $250 (for a doctor available on call to answer questions) to $4,500 (for a doctor who spoke at an in-person program). Salix paid more than 500 physicians honoraria for serving as speakers about their products, with dozens of physicians earning more than $50,000, and several earning more than $100,000.
The government joined two private whistleblower lawsuits that had previously been filed under seal pursuant to the False Claims Act.
More than 260 Zofran birth defects lawsuits continue to move forward in the federal multidistrict litigation now underway in U.S. District Court, District of Massachusetts. The parties have jointly submitted proposed Master Long and Short Form Complaints.
The Master Long Form Complaints are for plaintiffs who file cases involving the name brand drug, and another for those involving generic versions of ondansetron.
The Master Complaints will detail all the allegations common to the lawsuits pending in the litigation.
The cases are consolidated in MDL2657, Zofran (Ondansetron) Products Liability Litigation.
“The use of Master Long and Short Form complaints is standard procedure in a multidistrict litigation, and will streamline the process for filing a claim in this proceeding,” says Sandy A. Liebhard, a partner at Bernstein Liebhard LLP.
Zofran is an anti-nausea medication that has been approved for use in post-op surgery patients or those undergoing certain cancer treatments. The lawsuits accuse GlaxoSmithKline of concealing hundreds of birth defects reports involving babies who were exposed to the drug in-utero. The complaints also claim that as early as the 1980s, Glaxo was aware of animal studies suggesting that the active ingredient in Zofran could cross the placental barrier in mammals. The placental transfer of Zofran in humans was also confirmed in a study involving 41 pregnancies, according to the lawsuits.
Zofran has never been approved to treat pregnancy-related nausea and vomiting. Yet according to an analysis recently published in the American Journal of Obstetrics and Gynecology, around 1 million expectant women are prescribed the medication or its generic equivalents every year for this purpose. Zofran lawsuits point out that in 2012, GlaxoSmithKline agreed to pay $3 billion to resolve illegal marketing charges with the U.S. Department of Justice that involved a number of its medications. Among other things, the company had been accused of illegally promoting Zofran as an off-label treatment for expectant mothers suffering from pregnancy-related nausea and vomiting.

References: v. 
 v. 
 v. 
 v. 
 v. 
 v.