Baum Hedlund Urges DOJ to Investigate Celexa/Lexapro Clinical Trials

How Forest Misled the FDA, DOJ, USAO, and the Public about the Results of Celexa Study MD-18

January 24, 2018

Gregg Shapiro, Esq.
Chief of the Affirmative Civil Enforcement Unit
United States Attorney’s Office
District of Massachusetts
1 Courthouse Way, Suite 9200
Boston, MA 02210

Re.      How Forest Misled the FDA, DOJ, USAO, and the Public about the Results of Celexa Study MD-18

Dear Mr. Shapiro:

On September 15, 2010, Forest Laboratories, Inc. and Forest Pharmaceuticals, Inc. (“Forest”) entered into a series of agreements with the United States Attorney’s Office for the District of Massachusetts (“USAO”).

First, Forest agreed to plead guilty to one count of obstruction and two counts of distributing a misbranded drug under the Food, Drug, and Cosmetic Act. The third count specifically related to Forest promoting the use of the antidepressant Celexa (citalopram) for use in children and adolescents between 1998 and 2002.  The plea agreement imposed criminal fines of $39,500,000 for Celexa’s off-label promotion.  Second, Forest entered into a civil settlement agreement to resolve various qui tam False Claims Act lawsuits.  The settlement resolved, in part, allegations of fraudulent off-label promotion for both Celexa and Lexapro (escitalopram) for children and adolescents between 1998 and 2005.  Forest agreed to pay $149,158,057.66 to settle these claims.  Third, Forest entered into a corporate integrity agreement to address Forest’s promotional conduct for a period lasting five years.  Each agreement was contingent on the others and each agreement required complete honesty from Forest.

We have been litigating various cases against Forest related to the off-label promotion of Celexa and Lexapro for pediatric use for some years now—inspired by the USAO’s original investigation—in a multidistrict litigation proceeding in the District of Massachusetts.  Over the past several years, our litigation has revealed that the scope and extent of Forest’s fraud was not honestly disclosed to the USAO (or, to the Food and Drug Administration) and that Forest misrepresented material facts underlying the USAO’s prosecution.  Documents and testimony obtained in our litigation have been unsealed, over Forest’s objection, and we have prepared a detailed memorandum outlining Forest’s misconduct and fraud with the hope the USAO will consider reopening its investigation.  Obviously, we are not an unbiased source of information, however, we believe the documents and testimony speak for themselves.

For example, a central feature of Forest’s wrongful conduct, which formed the basis of the government’s investigation, involved the promotion and dissemination of a “positive” Celexa double-blind, placebo-controlled clinical trial in children and adolescents, MD-18, and the suppression of a negative Celexa double-blind, placebo-controlled clinical trial in adolescents, Study 94404.  However, unsealed documents and testimony show that the “positive” MD-18 study was not actually positive, and that Forest misled the FDA, the USAO, and the public about this fact.  Specifically, MD-18 was only able to achieve a positive result by including nine patients in the study that were, as Forest’s medical director put it, “automatically unblinded” due to a dispensing error.  In fact, when the mishap occurred, Forest told the FDA that it would exclude these patients from the primary results.  However, when Forest learned it needed the unblinded patients to achieve a positive result, i.e., to show that Celexa outperformed a sugar pill, Forest snuck the patients back into the results, and falsely told the FDA the patients were not actually unblinded.

One internal document, in particular, reveals that this was deliberate fraud.  Amy Rubin, a Forest Regulatory Affairs Manager, characterized the dispensing error as having “the potential to cause patient bias” in a draft letter to be sent to the FDA to disclose the unblinding problem.  Dr. Charles Flicker, the Senior Medical Director overseeing MD-18, did not approve of this language, stating: “Altho ‘potential to cause bias’ is a masterful stroke of euphemism, I would be a little more up front about the fact that the integrity of the blind was unmistakenly [sic] violated.”  Ms. Rubin responded: “Thanks for the compliement [sic]. Part of my job is to create ‘masterful’ euphemisms to protect Medical and Marketing.”  Thus, not only was the disclosure to the FDA dishonest, it was, according to a Forest Regulatory Affairs manager, her job to mislead the FDA and protect medical and marketing.

This “masterful euphemism” language was ultimately sent to the FDA.  When we deposed Dr. Thomas Laughren, the former official at the FDA who reviewed this study and who, within six months after leaving the FDA, was working as a testifying expert for Forest, he testified that he believed at the time he reviewed the study that there had been no unblinding and, when shown our documents and testimony, that Forest did not honesty disclose the situation to him.

The gravity of this misconduct becomes even more acute when one considers that Lexapro was ultimately approved by the FDA for adolescent depression in 2009 based on the supposedly “positive” results of MD-18.  Dr. Laughren personally approved the new indication for Lexapro and testified that, if MD-18 was negative, he would not have approved it.  It is our understanding that this approval weighed heavily into the USAO’s decision to settle their case against Forest.

We urge you to review the enclosed memorandum and accompanying evidence and consider reopening your investigation of Forest related to its promotion of Celexa and Lexapro for pediatric use.  We would be happy to answer any questions you may have or to meet you in person to walk you through the evidence.

Sincerely,

BAUM HEDLUND ARISTEI & GOLDMAN, P.C.

R. Brent Wisner

MEMORANDUM

How Forest Misled the FDA, USAO, and the Public about the Results of Celexa Study MD-18

January 24, 2018

By:
R. Brent Wisner, Esq.
[email protected]
Michael L. Baum, Esq.
[email protected]

BAUM HEDLUND ARISTEI & GOLDMAN, P.C.
12100 Wilshire Blvd., Ste 950
Los Angeles, CA 90049
(310) 207-3233

TABLE OF CONTENTS

PART I: EXECUTIVE SUMMARY

PART II: CELEXA PEDIATRIC CLINICAL TRIALS

  1. Celexa Study 94404 Was a Negative Clinical Trial
  2. Table 1 — Celexa Study 94404 Efficacy Results
  3. Celexa Study MD-18 Was a Negative Clinical Trial, but Forest Misled the FDA about the Results
  4. Table 2 – Celexa Study MD-18 Efficacy Results
    1. General Overview of MD-18 Study
    2. At the Beginning of the Trial, a Packaging Error Caused Nine Patients, and their Investigators, to Become Unblinded
    3. Celexa Study Dispensing Diagram
    4. Forest Knowingly Misled the FDA about the Nature of the Unblinding by Using, As Forest Regulatory Affairs Manager Put It, “Masterful Euphemisms” to “Protect Medical and Marketing”
    5. Despite Misrepresenting the Unblinding to the FDA, Forest Promised to Exclude the Data from the Patients from Its Primary Efficacy Analysis
    6. Forest Reneged on its Promise to Exclude the Unblinded Patients from the Primary Efficacy Results and, Again, Misrepresented the Unblinding in MD-18’s Final Study Report
    7. The FDA Never Fully Considered the Unblinding Issue and a Reasonable Regulator at the FDA Could Review this New Information and Conclude Study MD-18 Was Negative
    8. Forest Also Misled the FDA about the Results of the Secondary Endpoints
    9. Table 3 — Comparison of MD-18 Study Report & Dr. Heart Medical Review

PART III: FOREST USED FALSE RESULTS FROM MD-18 TO PROMOTE PEDIATRIC USE OF CELEXA AND LEXAPRO

PART IV: THE LEXAPRO PEDIATRIC TRIALS

  1. Lexapro Study MD-15 Was a Negative Clinical Trial
  2. Table 4 – Lexapro Study MD-15 Efficacy Results
  3. Lexapro Study MD-32 Was a “Positive” Clinical Trial for Adolescents, but Did Not Show a Meaningful Difference between Lexapro and Placebo

PART V: FOREST LEVERAGED THE FALSE RESULTS OF MD-18 TO OBTAIN AN ADOLESCENT INDICATION FOR LEXAPRO

PART VI:  FOREST USED THE FALSE ASSERTION THAT MD-18 WAS POSITIVE AND THE FDA’s APPROVAL FOR LEXAPRO TO NEGOTIATE REDUCED PENALTIES IN USAO CASE