Interesting development with regards to some of the lawsuits going on in the U.S. I read the Punitive Damages Order. Things that make you go hmmmmmmmmmmm!

The Basic Product Information sheet was circulated to BIPI and the rest of BI’s operating
companies in September 2004 for incorporation into Mirapex product labeling worldwide. (Pl.
Ex. 85.) BIPI did not put a warning on the product label in the United States indicating that
pathological gambling symptoms subside upon treatment discontinuation. Rather, BIPI added
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only “pathological gambling” to the “post-marketing experience” section of the label. (Pl. Ex.
86 at 7166-72.) The text stated that: “[b]ecause these reactions are reported voluntarily from a
population of uncertain size, it is not always possible to reliably estimate their frequency or
establish a causal relationship to drug exposure.” (Pl. Ex. 90 at 7170-71.)
Plaintiffs allege that BIPI then publicly denied that there was a causal link between
Mirapex and compulsive behaviors, in the face of contrary conclusions from its parent company
and with the knowledge that there had been reports of compulsive gambling in the clinical trials.

On November 30, 2004, Dr. Kirk Shepard appeared on CBS News in Cedar Rapids, Iowa and
communicated that “[t]here is no evidence of a causal effect between pramipexole and
compulsive behavior such as gambling” and that “[i]n the trials . . . there were no cases of
compulsive behavior.” (Pl. Ex. 91.) Plaintiff’s Exhibit 91 is an internal email summarizing Dr.
Shephard’s “key points.” (Id.) On December 16, 2004, Dr. Zerban, with BI Germany, sent an
email to Dr. Shepard and Dr. Corsico (BIPI’s Director of Drug Safety), stating that:
the attached document (CBS Q&A Final) addresses the question: Is Miarapex
causing the compulsive gambling? We do have indication of a causal
relationship. This is why we recommend a discontinuation of Pramipexole in our
corporate label, if pathological gambling is observed. I have already send a copy
of the report dealing with the issue of pathological gambling to Kirk. (Pl. Ex. 93.)

BIPI’s statement that there was no evidence of a causal relationship between Mirapex
and gambling was also reported on Good Morning America on December 23, 2004 where it was
reported that “[t]he manufacturer of Mirapex told ABC News in a written statement that . . . it
does not believe there is proof of a causal relationship between the product and gambling.” (Pl.
Ex. 94.) BIPI’s position that there is no link was reported in numerous other outlets, including
NBC News Baltimore (February 10, 2005), Associated Press (July 12, 2005). BIPI also emailed
a statement to the Wall Street Journal in July of 2005 stating that “there is no scientific evidence
of a causal effect between pramipexole and compulsive behavior[.]” (Pl. Ex. 98.)
Plaintiffs allege that BIPI also failed to report important information to the FDA in July
2005. At that time, the FDA requested information about reports of gambling that BIPI had
15
received. (Pl. Ex. 113.) In the letter sent to the FDA in response to their request, BIPI did not
mention BI’s Clinical Expert Statement which concluded that there was a clear
pharmacodynamic effect of Pramipexole on pathological gambling. (Pl. Ex. 78.) BIPI did not
disclose that BI had added a warning to labels outside the United States indicating that
pathological gambling was a possible side effect that was reversible upon discontinuation of the
treatment. (Id.) BIPI also failed to report three cases of compulsive gambling from the clinical
trials. (Bray Aff. ¶¶ 5-8.)
Plaintiffs contend that BIPI delayed conducting a study. In October of 2003, a panel of
expert consultants recommended that a study should be conducted on impulse control behaviors
in Parkinson’s Disease patients. (Pl. Ex. 72.) The panel explained that “such a study could
document the broad range of compulsive disorders in these patients and help determine if the
disorders are disease or treatment-related. Id. In April 2004, another expert panel made the
same recommendation. (Pl. Ex. 73.) Representatives from Pfizer and BIPI were present at this
meeting. (Id.) In May 2005, one expert, Dr. Olanow, was concerned that BIPI “had not taken
action steps on the issue despite advice [sic] provided by consultants.” (Pl. Ex. 75.) In June
2005, Dr. Olanow voiced his concern again, indicating that the study was “twelve months
overdue as it is.” (Pl. Ex. 76.) BIPI convened another expert meeting in July 2005. (Pl. Ex. 77.)
BIPI did not finalize the protocol for the study until July 2006, (Pl. Ex. 80), and BIPI will not
have the study completed and the report on it issued until March 2009. (Pl. Ex. 81.)
Plaintiffs’ allegations and the evidence presented in support constitute a prima facie case
that BIPI acted with deliberate or conscious disregard for the rights or safety of others.
Therefore, the Court finds that Plaintiffs may allege punitive damages against BIPI.
2. Plaintiff’s Evidence Against, Pharmacia & Upjohn, LLC, Pharmacia and Pfizer
a. Pharmacia & Upjohn, LLC
Plaintiffs allege that Pharmacia and Upjohn knew all along that Mirapex caused
compulsive behaviors and failed to research the issue or warn patients about the possible side effect


Plaintiff has presented evidence that Upjohn filed Mirapex Investigational New Drug application for the treatment of depression where it acknowledged that Mirapex targeted the
dopamine function and the mesolimbic pathways involved with motivation and reward resulting in mood enhancement and reduced depression. (Pl. Ex. 4.) Upjohn noted that dopamine
agonists caused compulsive behaviors in animals such as compulsive gnawing, licking, biting
and sniffing. (Id. at 8729.)

Plaintiffs have also presented evidence that Upjohn was also part of an effort to suppress Mirapex studies.

In February 1994, individuals on the BI/Upjohn Development team agreed that
“no [pramipexole] will be sent to the NIDA [National Institute on Drug Abuse] as we would not wish to be confronted with this data regarding addiction models[.]” (Pl. Ex. 10 at 9165.) BI and
Upjohn representatives also decided not to give a sample of pramipexole to researcher Torben
Kling-Peterson, who was conducting an intracranial self-stimulation model, because they did not
want to risk pramipexole being associated in any way with “addiction.” (Pl. Ex. 14.) They also
agreed that Mirapex should not be provided to external investigators “for models associated with
addiction.” (Id.) Plaintiffs allege that BI and Upjohn then worked together to suppress mention
of the terms “addiction” and “positive reinforcement” from a proposed abstract and presentation about Mirapex. (Pl. Ex. 17.)

The researcher eventually agreed to delete the terms from his
abstract and the discussion from his presentation and BI then agreed to release the abstract for
publication. (Id. at 7648.)
Plaintiffs also contend that the numerous reports of compulsive gambling from the clinical trials should have induced Upjohn and BIPI to research the issue further and to warn patients about the possible side effect. BI, BIPI and Upjohn were studying and developing
Mirapex between February 16, 1993 and December 26, 1995, during which time a number of cases of compulsive behavior were reported. See Section III.B supra. According to Defendant’s
chart, on July 2, 1997, BIPI entered into a Co-Promotion agreement with Pharmacia and Upjohn for marketing of Mirapex and both companies jointly marketed Mirapex until May 1, 2005.
17
During this time, there were also a number of cases of compulsive behavior reported. See
Section III.B.1 supra.
Plaintiffs have presented prima facie evidence that Pharmacia and Upjohn failed to
properly study possible side effects, failed to warn and attempted to suppress studies of Mirapex
as it relates to addiction. This evidence, if unrebutted, could be relied upon at trial to find that
Pharmacia and Upjohn disregarded the high probability of injury to the rights or safety of others.
b. Pharmacia
Plaintiffs allege that Pharmacia remained silent about compulsive gambling as a side
effect of Mirapex despite receiving many reports of gambling from patients and doctors.
Pharmacia received the following reports:
• In early September, 1996, patient 2421 in the M/2730/0002 trial developed
“compulsive behavior” and was hospitalized. (Ex. 25, BIPISELINSKY01147027
at 7152.) The patient was hospitalized for “depression with
suicidal ideation,” because she “had been having an ongoing problem with
gambling and has again spent money she didn’t have and overdrawn her bank
account again.” The records describe the patient as suffering “what she felt is a
gambling addiction.” (Ex. 26, BIPI-PFIZER-SELINSKY0042987.) But when
Pharmacia reported the event to the FDA nearly two years after her
hospitalization, they failed to disclose the true nature of the adverse
event—gambling addiction—instead reporting only that she suffered from
“anxiety” and “stress.” (Ex. 27, BIPI-PFIZER-SELINSKY00199704 at 9812.) In
fact, her gambling addiction has never been reported to the FDA. (Ex. 28, Tr.
Reidies Dep. at 109-115.)
• In August 2002, Pharmacia received a report that a woman taking Mirapex had
developed “compulsive gambling.” (Pl. Ex. 51 at 6819-20.)•


In September 2002, Pharmacia received a report that a woman and her husband on Mirapex developed gambling addiction and were “in financial ruin.” (Id. at
6825-28.) The woman also reported that she knew four other people taking
Mirapex who developed gambling addictions. (Id.at 6829-30.)
• In March 2003, Pharmacia received a report that a man who was on Mirapex had
developed a problem with gambling, and was “putting that activity before
business, paying bills, [or] gathering information for taxes[.]” (Id. at 6859-60.)
• In May 2003, Pharmacia received a report that a woman had been taking Mirapex
and had developed “a serious gambling compulsion, which caused her complete
financial ruin.” (Ex. 52 at 5345.) “After she was off the product for one month
18
she returned to normal and did not have a gambling compulsion any longer.”
(Id.)
Pharmacia did report this last event to the FDA but did not take any steps to warn
patients or doctors that compulsive behavior may be linked to Mirapex. Plaintiffs also allege,
that Pharmacia, along with the rest of the Defendants failed to properly study compulsive
behaviors as a possible side effect of Mirapex. These allegations and the evidence presented in
support establish a prima facie case that Pharmacia acted with disregard for the high probability
of injury to the rights or safety of others.
c. Pfizer
Plaintiffs allege that Pfizer learned in August of 2003 that three doctors who were
prescribing Mirapex, Dr. Stern, Dr. Ravin and Dr. Lieberman had patients develop gambling
addictions. (Pl. Ex. 61; Pl. Ex. 64) Pfizer did not report these cases to the FDA. (Pl. Ex. 42, Tr.
Castro Dep. at 239-50; Ex. 59 Tr. Taylor Dep. at 149.)


On January 30, 2004, after BI took over
reporting responsibilities from Pfizer, it concluded that Pfizer’s failure to report these cases
“placed BI in a non-compliance situation” because these reports were not made when Pfizer first
learned of them. (Pl. Ex. 111.)

Even though Pfizer did not report Dr. Lieberman or Dr. Ravin’s
cases to the FDA, in November 2003, it did share the existence of those cases with its “communications team for . . . planning purposes.” (Pl. Ex. 70.) When Pfizer shared this
information with its public relations consultant, Weber Shandwick, the consultant’s crisis
management proposal identified the doctors as “threats.” (Pl. Ex. 71.) That Pfizer failed to
timely report to the FDA what it had learned from Doctors Stern, Ravin and Lieberman, but
instead treated the information as a public relations issue constitutes prima facie evidence that
Pfizer acted with deliberate disregard for the rights and safety of others.