Botox maker to pay $600M to resolve investigation

2010 report posted for filing

 

 

Botox maker to pay $600M to resolve investigation

 

By MATTHEW PERRONE, AP Health Writer Matthew Perrone, Ap Health Writer

Thu Sep 2, 4:01 am ET

 

WASHINGTON – Allergan Inc., the maker of wrinkle-smoothing Botox, has agreed to pay $600 million to settle a yearslong federal investigation into its marketing of the top-selling, botulin-based drug.

 

The Justice Department and the company said Wednesday in a statement it will plead guilty to one misdemeanor charge of “misbranding,” in which the company’s marketing led physicians to use Botox for unapproved uses. Those included the treatment of headache, pain, spasticity and cerebral palsy in children.

 

Companies are prohibited from promoting drugs for unapproved, or “off-label,” uses.

 

Allergan said it will pay $375 million in connection with the plea, which includes the forfeiture of $25 million in assets. Additionally, the company will pay $225 million in civil fines — $210 million to the federal governments and the rest to several states — related to the investigation, although the company denies liability for the civil claims.

 

Allergan, based in Irvine, Calif., also struck an agreement with the Department of Health and Human Services’ Office of the Inspector General that requires the company to submit compliance reports, and to post on its website any payments to doctors, such as honoraria, travel or lodging.

 

Allergan “paid kickbacks to induce physicals to inject Botox for off-label uses and Allergan also taught doctors how to bill for off-label uses, including coaching doctors how to miscode Botox claims leading to millions of dollars of false claims being to submitted to federal and state programs,” Assistant Attorney General Tony West said.

 

Allergan officials will make their first appearance in federal court on Thursday. The settlement is not official until approved by a federal judge.

 

“The FDA had approved therapeutic uses of Botox for only four rare conditions, yet Allergan made it a top corporate priority to maximize sales of far more lucrative off-label uses that were not approved by the FDA,” said Sally Yates, U.S. Attorney for the Northern District of Georgia. “Allergan further demanded tremendous growth in these off-label sales year after year, even when there was little clinical evidence that these uses were effective.”

 

The investigation was sparked by a whistleblower complaint, officials said, and five whistleblowers will split $37.8 million of the government’s share of the settlement.

 

Allergan’s product sales topped $4.4 billion in 2009, with Botox accounting for more than $1.3 billion of that total.

 

The Justice Department’s investigation covered Allergan’s marketing of Botox from 2001 through at least 2008.

 

Wells Fargo analyst Larry Biegelsen said the settlement is a positive for the company’s stock because it removes uncertainty.

 

“We view the settlement as a positive for Allergan as it provides cost certainty … and eliminates additional related litigation cost,” Biegelsen wrote in a note to investors.

 

In recent years, federal investigators have reached multibillion dollar settlements with Pfizer, Eli Lilly and other drug companies over their marketing practices.

 

Botox is most famous for its ability to smooth frown lines on aging foreheads, but the drug — introduced in 1989 — is also approved to treat neck spasms, eye muscle disorders and excessive underarm sweating.

 

Last year the drug won approval to treat spasms in the elbows, wrists and fingers. The drug is also widely used off-label to treat cerebral palsy in children as well as in adults, and Allergan says it is in discussions with U.S. health regulators to approve the use of Botox for children with the neuromuscular disorder.

 

In guidelines published earlier this year, the American Academy of Neurology endorsed Botox as an “effective and generally safe treatment” for children with cerebral palsy. While the use is not approved by the Food and Drug Administration, the guidelines stated that there are more studies supporting Botox than other movement-disorder drugs.

 

Botox works by blocking the connections between nerves and muscle, temporarily paralyzing muscles that cause wrinkles as well as certain types of spasms. The drug is a purified form of botulinum, one of the most toxic substances in the world.

 

As part of the settlement, Allergan agreed to drop a lawsuit against the FDA in which the company pressed for greater leeway to discuss off-label uses with doctors.

 

The company argued it had a First Amendment right to educate doctors about how to safely use Botox, even for uses that are not currently approved. FDA’s rules are designed to stop companies from promoting drugs for uses that haven’t been federally confirmed as safe and effective.

 

Some legal experts speculated that Allergan’s lawsuit against FDA was primarily aimed at gaining leverage in its negotiations with the Justice Department, which was a separate matter.

 

Shares of Allergan rose $1.86, or 3 percent, to $63.28.

 

Ralph’s Note – Unless they start issuing criminal charges, these companies will always count the fines as nothing more than the cost of doing business.

Only 15% of Whistleblower Off Label Drug Complaints have Adequate Financial Disclosure

Contact: Sumrina Yousufzai syousufzai@plos.org 415-568-3164 Public Library of Science

COI declarations and off-label drug use

Conflict-of-interest statements made by physicians and scientists in their medical journal articles after they had been allegedly paid by pharmaceutical manufacturers as part of off-label marketing programs are often inadequate, highlighting the deficiencies in relying on author candidness and the weaknesses in some journal practices in ensuring proper disclosure, according to a study by international researchers published in this week’s PLOS Medicine. Off-label marketing is the promotion by a manufacturer of a drug for use in a condition or age group, or in a dose or form of administration that has not been specifically approved by a drugs regulatory body; it is illegal in the United States.

In an analysis led by Aaron Kesselheim from Brigham and Women’s Hospital in Boston, the authors from the US and Australia found that overall, only one in seven authors reported by whistleblowers to be involved in off-label marketing activities fully disclosed their conflict of interest in published articles.

The authors reached these conclusions by examining 26 whistleblower complaints of illegal off-label promotion and identified the 91 doctors and scientists recorded as being involved in this practice. The researchers found 39 (43%) of these 91 experts had authored 404 publications related to the drugs at issue in the complaints. However, only 62 (15%) of these articles had adequate disclosures.  Among the articles without adequate disclosures, 43% (148) had no disclosure at all, 4% had statements denying any conflicts of interest, 40% had disclosures that did not mention the drug manufacturer, and 13% had disclosures that mentioned the manufacturer but inadequately conveyed the nature of the relationship between author and drug manufacturer reported in the complaint.

The authors argue that such failures in relation to off-label marketing schemes are especially troubling because off-label use is an area of clinical practice in which opinion is likely to be divided about appropriate care and there is no guidance from regulatory authorities.  Therefore, high-profile ”opinion leaders” may exert considerable influence on prescribing practices through their publications.  The authors argue: “More adequate disclosure of financial ties in these situations would give readers an opportunity to weigh the potential for bias.”

The authors conclude: “Our findings suggest that approaches to controlling the effects of conflicts of interest that rely on author candidness and variable policing by journals have fallen short of the mark. Readers are left with little choice but to be sceptical.”

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Funding:  ASK is supported by a career development award from the Agency for Healthcare Research & Quality (K08HS18465-01), and a Robert Wood Johnson Foundation Investigator Award in Health Policy Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared the following competing interests: ASK was co-chair of a conference entitled Conflicts of Interest in the Practice of Medicine: A National Symposium sponsored by the American Society of Law, Medicine, and Ethics, the Highmark Foundation, the Jewish Healthcare Foundation, and the University of Pittsburgh; ASK was paid a small honorarium for his effort. In 2008-2009, ASK served as an expert witness for the state of Texas in a case against Merck alleging inappropriate promotion of rofecoxib (Vioxx), and ASK served as an expert witness for a class of individual plaintiffs in a case against AstraZeneca alleging inappropriate promotion of esomeprazole (Nexium). All other authors have declared no competing interests.

Citation: Kesselheim AS, Wang B, Studdert DM, Avorn J (2012) Conflict of Interest Reporting by Authors Involved in Promotion of Off-Label Drug Use: An Analysis of Journal Disclosures. PLoS Med 9(8): e1001280. doi:10.1371/journal.pmed.1001280

IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER (THIS LINK WILL BECOME LIVE WHEN THE EMBARGO LIFTS):

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001280

PRESS-ONLY PREVIEW OF THE ARTICLE:

http://www.plos.org/media/press/2012/plme-09-08-kesselheim.pdf

CONTACT: Aaron S. Kesselheim Brigham and Women’s Hospital and Harvard Medical School Massachusetts, United States of America akesselheim@partners.org

Dangerous experiment in fetal engineering (MUST READ)

Public release date: 2-Aug-2012


Dangerous experiment in fetal engineering

Risky prenatal use of steroid to try to prevent intersex, tomboys and lesbians

CHICAGO — A new paper just published in the Journal of Bioethical Inquiry uses extensive Freedom of Information Act findings to detail an extremely troubling off-label medical intervention employed in the U.S. on pregnant women to intentionally engineer the development of their fetuses for sex normalization purposes.

The paper is authored by Alice Dreger, professor of clinical medical humanities and bioethics at Northwestern University Feinberg School of Medicine and is co-authored by Ellen Feder, associate professor of philosophy and religion at American University, and Anne Tamar-Mattis, executive director of Advocates for Informed Choice.

The pregnant women targeted are at risk for having a child born with the condition congenital adrenal hyperplasia (CAH), an endocrinological condition that can result in female fetuses being born with intersex or more male-typical genitals and brains. Women genetically identified as being at risk are given dexamethasone, a synthetic steroid, off-label starting as early as week five of the first trimester to try to “normalize” the development of those fetuses, which are female and CAH-affected. Because the drug must be administered before doctors can know if the fetus is female or CAH-affected, only one in eight of those exposed are the target type of fetus.

The off-label intervention does not prevent CAH; it aims only at sex normalization. Like Diethylstilbestrol (DES) — which is now known to have caused major fertility problems and fatal cancers among those exposed in utero — dexamethasone is a synthetic steroid. Dexamethasone is known — and in this case intended — to cross the placental barrier and change fetal development. Experts estimate the glucocorticoid dose reaching the fetus is 60 to 100 times what the body would normally experience.

The new report provides clear evidence that:

  • For more than 10 years, medical societies repeatedly but ultimately impotently expressed high alarm at use of this off-label intervention outside prospective clinical trials, because it is so high risk and because nearly 90 percent of those exposed cannot benefit. 
  • Mothers offered the intervention have been told it “has been found safe for mother and child” but in fact there has never been any such scientific evidence. 
  • The U.S. Food and Drug Administration has indicated it cannot stop advertising of this off-label use as “safe for mother and child” because the advertising is done by a clinician not affiliated with the drug maker. 
  • A just-out report from Sweden in the Journal of Clinical Endocrinology and Metabolism documents a nearly 20 percent “serious adverse event” rate among the children exposed in utero
  • Clinician proponents of the intervention have been interested in whether the intervention can reduce rates of tomboyism, lesbianism and bisexuality, characteristics they have termed “behavioral masculinization.” 
  • The National Institutes of Health has funded research to see if these attempts to prevent “behavioral masculinization” with prenatal dexamethasone are “successful.” 
  • The United States’ systems designed to prevent another tragedy like DES and thalidomide — involving de facto experimentation on pregnant women and their fetuses — appear to be broken and ineffectual.
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The paper is available for free download at: http://www.springerlink.com/content/m1523l7615744552/?MUD=MP

Contact: Marla Paul
Marla-Paul@northwestern.edu
312-503-8928
Northwestern University