Wendell et al v. Johnson & Johnson et al

Filing 232

ORDER by Judge Claudia Wilken DENYING CENTOCOR AND JOHNSON AND JOHNSONS MOTION FOR SUMMARY JUDGMENT, GRANTING PLAINTIFFS MOTION FOR RECONSIDERATION, DENYING ABBOTT, TEVA AND PARS MOTIONS FOR SUMMARY JUDGMENT, AND GRANTING GSKS MOTION FOR SUMMARY JUDGMENT. (ndr, COURT STAFF) (Filed on 7/25/2012)

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IN THE UNITED STATES DISTRICT COURT

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FOR THE NORTHERN DISTRICT OF CALIFORNIA

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STEPHEN WENDELL and LISA WENDELL,
as successors in interest to MAXX
WENDELL, deceased,

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United States District Court
For the Northern District of California

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Plaintiffs,
v.
JOHNSON & JOHNSON; CENTOCOR,
INC.; ABBOTT LABORATORIES;
SMITHKLINE BEECHAM d/b/a
GLAXOSMITHKLINE; TEVA
PHARMACEUTICALS USA; GATE
PHARMACEUTICALS, a division of
TEVA PHARMACEUTICALS USA; and PAR
PHARMACEUTICAL, INC.,
Defendants.
________________________________/

No. C 09-04124 CW
ORDER DENYING
CENTOCOR AND
JOHNSON AND
JOHNSON’S MOTION
FOR SUMMARY
JUDGMENT, GRANTING
PLAINTIFFS’ MOTION
FOR
RECONSIDERATION,
DENYING ABBOTT,
TEVA AND PAR’S
MOTIONS FOR
SUMMARY JUDGMENT,
AND GRANTING GSK’S
MOTION FOR SUMMARY
JUDGMENT

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This is a pharmaceutical products liability case in which

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Plaintiffs Stephen and Lisa Wendell have sued as successors-in-

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interest to their deceased son Maxx Wendell.

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brought strict liability and negligence claims alleging that

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Defendants failed to provide adequate warnings of the risk of

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hepatosplenic T-cell lymphoma presented by certain drugs--Humira,

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Remicade and 6-mercaptopurine (6-MP).1

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Plaintiffs have

On March 2, 2011, GlaxoSmithKline LLC (GSK)2 moved for

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summary judgment, but the Court denied the motion without

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prejudice pursuant to Federal Rule of Civil Procedure 56(d).

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On

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6-mercaptopurine is also known as mercaptopurine and
Purinethol.
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GSK was formerly known as and erroneously served and sued
in this action as SmithKline Beecham d/b/a GlaxoSmithKline.

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June 23, 2011, the Court approved the parties’ stipulation to

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vacate all case management deadlines and stay discovery until

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after the parties’ mediation or the ruling on Defendants’ motions

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for summary judgment, whichever occurs later, and at that time to

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determine a proposed schedule for the remainder of the case.

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Subsequently, Defendants Abbott Laboratories, GSK, TEVA

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Pharmaceuticals USA, which includes Gate Pharmaceuticals, and PAR

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Pharmaceutical, Inc., moved for summary judgment on the grounds

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that Plaintiffs lacked evidence to establish proximate causation.

United States District Court
For the Northern District of California

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Docket Nos. 177, 179, 183 and 185.

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distributes and sells Humira.

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have been resold in California and has marketed and advertised the

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product under the brand name Purinethol.

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labeled, packaged and marketed Purinethol in the United States

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prior to July 2003.

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Defendants argued that Plaintiffs lacked evidence to show that a

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different warning would have changed the treating physician’s

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decision to prescribe Humira and 6-MP to Maxx.

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& Johnson and its wholly owned subsidiary, Centocor, Inc., which

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manufactured, marketed, sold and distributed Remicade, did not

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file motions for summary judgment at that time.

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2011, the Court granted summary judgment in favor of Abbott, GSK,

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TEVA and PAR.

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Abbott manufactures, markets,

TEVA distributes 6-MP products that

GSK manufactured,

PAR distributes 6-MP in California.

These

Defendants Johnson

On December 15,

After the Court’s ruling, Johnson & Johnson and Centocor

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moved for summary judgment, arguing that Plaintiffs lacked

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evidence to establish that a failure to warn of the risk

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associated with Remicade caused harm to Maxx.

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Johnson and Johnson also argued that it was not involved with the
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Docket No. 205.

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research, production, marketing or distribution of the drug.

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After briefing on the second motion for summary judgment was

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completed, Plaintiffs moved for leave to file a motion for

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reconsideration of the Court’s December 15, 2011 order.

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No. 220.

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connection with the second motion for summary judgment warranted

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reconsideration.

Abbott, GSK and TEVA opposed the request for

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reconsideration.

On April 12, 2012, the Court granted Plaintiffs’

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request for leave to file a motion for reconsideration and allowed

United States District Court
For the Northern District of California

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Docket

Plaintiffs argued that new evidence presented in

Defendants to file additional briefing.
Having considered all of the parties’ submissions and oral

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argument, the Court denies Centocor and Johnson and Johnson’s

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motion for summary judgment.

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Plaintiffs’ motion for reconsideration of its December 15, 2011

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order and, upon reconsideration, denies Abbott’s, TEVA’s and PAR’s

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motions for summary judgment.

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2011 motion for summary judgment on the grounds that it

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discontinued its sales of Purinethol in 2003, before its risks

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were known.

In addition, the Court grants

The Court grants GSK’s March 2,

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BACKGROUND

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In the fall of 1998, Maxx was diagnosed with inflammatory

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bowel disease (IBD), and began receiving treatment from Dr. Edward

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Rich, a pediatric gastroenterologist at Kaiser Permanente in San

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Francisco.

Rich Dep. at 50:5-10, 59:22-60:1, 74:23-25.3

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3

The complete transcript of the deposition is located at
Docket No. 199.
3

1

Dr. Rich testified that it was not his “regular practice to

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look at drug labeling.”

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on medications from multiple sources, including conferences and

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large meetings with pediatric gastroenterologists and adult IBD

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specialists, as well as smaller regional meetings and dinner

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meetings with these colleagues.

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also gained knowledge about therapies from discussions with other

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professionals in the field, articles and occasional meetings with

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drug representatives.

Id. at 192:6-7.

He received information

Id. at 251:5-252:2.

Id. at 192:7-14.

Dr. Rich

He explained, “Generally

United States District Court
For the Northern District of California

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I’m looking at drug labeling or the PDR in medicines that I’m less

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familiar with.”

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With respect to the impact of drug labeling on his decisions

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regarding treatment, Dr. Rich testified, “Drug labeling is

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sometimes something I rely on when making decisions on drug use

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for patients.”

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labeling, it’s one of the things that is part of my decision-

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making process.”

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whether he ever relied on labeling information for 6-MP before

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prescribing it to patients.

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Id. at 190:21-23.

He stated, “When I read the

Id. at 191:20-22.

Dr. Rich could not remember

Id. at 282:2-283:2.

In June 1999, Maxx began taking 6-MP, an immunosuppressive

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medication.

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dosages of 6-MP, while attempting to wean Maxx from Prednisone, a

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steroid.

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Prednisone and 6-MP.

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Id. at 105:14-15.

Dr. Rich prescribed varying

However, as of May 2002, Maxx was still taking
Id. at 117:4-11.

At the time Dr. Rich prescribed 6-MP he was aware of a paper

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reporting the occurrence of lymphoma in adults taking the drug.

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Id. at 89:12-90:17.

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lymphoma occurrences reported in the study was one in one hundred

According to Dr. Rich, the frequency of

4

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adult patients taking 6-MP.

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this “significant,” prompting him to warn patients of a “small but

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non-zero increased risk of serious infections or malignancies”

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when discussing 6-MP treatment.

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testified that he may or may not have included the word “lymphoma”

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when providing the warning.

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Id. at 89:23-90:4.

Dr. Rich found

Id. at 89:2-90:17.

Dr. Rich

Id. at 89:7-12.

At an appointment with Maxx on May 8, 2002, Dr. Rich

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discussed in detail prescribing Remicade.

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Again, the goal in changing Maxx’s medication at this time was to

Id. at 117:4-118:1.

United States District Court
For the Northern District of California

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take him off steroids.

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Maxx received his first infusion of Remicade.

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148:16.

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three months thereafter, in combination with 6-MP.

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12, 157:9, 170:12-21.

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Id. at 151:17-152:9.

On July 10, 2002,
Id. at 147:24-

Maxx received infusions of Remicade approximately every
Id. at 155:4-

Dr. Rich considered Remicade, as well as Humira, part of a

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class of anti-tumor necrosis factor (TNF) drugs, also known as TNF

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inhibitors.

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testified that he “virtually always” informed his patients of a

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“nonzero increased risk” of serious infections and malignancies

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related to “immunosuppressives and anti-tumor necrosis factor

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drugs.”

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time he could not recall, he became aware of a study involving

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approximately 700 patients on Remicade therapy, a majority of whom

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had rheumatoid arthritis and a minority of whom had Crohn’s

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disease.

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serious infections and malignancies, including lymphomas, within

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that patient population.

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with an entry regarding Remicade in the 2002 Physicians’ Desk

Id. at 175:10-14, 176:9-17, 264:24-25, 265:2-3.

Id. at 123:6-10.

He

According to Dr. Rich, at a point in

Id. at 125:13-19.

The study reported incidents of

Id. at 125:20-126:1.

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This is consistent

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Reference, which included mention of a clinical study involving

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771 patients, seven of whom developed new or recurrent

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malignancies, including lymphoma.

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PDR also stated that “the observed rates and incidents [of these

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malignancies] were similar to those expected for the population.”

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Id. at 133:10-12.

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reports on the risk of therapies combining Remicade and 6-MP.

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at 132:10-12.

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Id. at 133:2-12.

However, the

According to Dr. Rich, in 2002 there were no
Id.

In February 2005, the first case report was published of an

United States District Court
For the Northern District of California

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IBD patient with hepatosplenic T-cell lymphoma who had received

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immunosuppressive therapy in combination with Remicade.4

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Declaration of Kevin Haverty in support of Plaintiffs’ Opposition,

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Ex. 4, Rosh Report, at 5.

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rare, incurable, aggressive cancer that is nearly always fatal.

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Id. at 2-3.

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hepatosplenic T-cell lymphoma reported to the federal Food and

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Drug Administration (FDA), six died.

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and Par’s Further Opposition to Plaintiffs’ Mot. for

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Reconsideration, Ex. 2, FDA Short Communication, at 265.

Hepatosplenic T-cell lymphoma is a

Of eight cases of young patients diagnosed with

Defendant Abbott Labs, TEVA

Each of

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4

The first case report was “Hepatosplenic T-cell lymphoma in
an adolescent patient after immunomodular and biologic therapy for
Crohn’s disease,” authored by Thayu M., Markowitz J.E., Mamula P.,
et al. (Thayu Report), and published in the Journal of Pediatric
Gastroenterology and Nutrition. The Thayu Report refers to
infliximab, another name for Remicade, see e.g., Jones Affidavit,
Ex. G, May 2006 Remicade Package Insert, at 1, and describes
immunomodulatory and biologic therapy as treatment combining 6-MP
and Remicade. A May 2007 report entitled, “Hepatosplenic T-cell
lymphoma in adolescents and young adults with Crohn’s disease: A
cautionary tale?,” authored by Rosh J.R., Gross T., Mamula P.,
Griffiths A. and Hymans J. (Rosh Report), referred to the Thayu
Report as the first such case report. Haverty Dec., Ex. 4 at 5.
6

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the patients succumbed to the cancer within a year or less from

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the time of diagnosis.

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Id. at 266.

In November 2005, Centocor submitted to the FDA a

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supplemental Biologic License Application (sBLA) seeking approval

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of a new use of Remicade for treatment of pediatric Crohn’s

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disease.

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Also in November 2005, Dr. Rich began to consider

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discontinuing Maxx’s Remicade treatment and discussed Humira with

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him.

Id. at 170:24-173:5.

Dr. Rich testified that in “late 2005”

United States District Court
For the Northern District of California

10

he became aware of a “complication” associated with Remicade,

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namely the occurrence of hepatosplenic T-cell lymphoma in

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adolescent and young adult patients taking Remicade with 6-MP.

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Id. at 204:21-205:22, 215:3-4.

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In his deposition, Dr. Rich was not asked directly about the

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source of his knowledge about the complication, but he testified,

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I knew this information before the black box warning
or messaging from the patient (verbatim). I was aware
of literature as it evolved. This is a very important
part of our treatment. And was aware from many
sources when cases first got--were first reported,
came to my attention. I believe that was sometime in
2005. I can’t tell you when . . .

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I can’t remember exactly the time course of what I
learned and where. At some point I became aware of
cases of hepatocellular [sic] T-cell lymphoma in young
males on combination therapy of Remicade and
immunosuppressive therapy. And at some point, there
was a report. I can’t--I don’t remember if it was
first at a meeting--I didn’t attend the meeting, if
that was true--or if it was an abstract or if it was
just a case report of a number of patients.
The number in my head is something like six patients
with this rare or uncommon lymphoma. And then at some
point there was an article on this, I believe. At
first it might have been a report and then an article,
7

1
2

but I can’t exactly be sure. And when the article
came out it was six to eight patients, and this was
before the black box warning came out.

3

Id. at 205:15-23; 206:12-207:5.

4

When asked whether any doctor had discussed a case of

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hepatosplenic T-cell lymphoma with him, Dr. Rich testified that he

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may have learned of such a case from a colleague in the East Bay

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and a doctor from Atlanta.

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recall the specific date or month when the conversations occurred.

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He testified repeatedly that he did not remember when his informal

Id. at 29:24-32:5.

Dr. Rich did not

United States District Court
For the Northern District of California

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discussion with the Atlanta-based physician occurred.

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point, he stated that the discussion may have occurred in the late

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1990s, but then retracted this and testified that he learned of

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the case “when patients with side effects were being reported, but

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not many, so that would be approximately the mid-2000s.”

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32:21-35:6.

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discussed with his regional pediatric gastroenterology group,

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which met quarterly, a pediatric gastroenterologist from the East

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Bay may have mentioned such a case.

19

At one

Id. at

Dr. Rich also testified that when Maxx’s case was

Id. at 15:5-25.

Maxx received an infusion of Remicade in November 2005 and

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then his final dose of Remicade in March 2006.

Id. at 182:15-14;

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197:16-199:7.

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of hepatosplenic T-cell lymphoma in IBD patients receiving

Between February 2005 and February 2007, nine cases

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8

1

combination therapy were confirmed, in addition to Thayu’s case.5

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Rosh Report at 5.

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In April 2006, as part of Centocor’s sBLA and the FDA’s

4

review of the application, a safety signal was identified for

5

hepatosplenic T-cell lymphoma.

6

As defined by the FDA in a guidance document, a safety signal

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“refers to a concern about an excess of adverse events compared to

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what would be expected to be associated with a product’s use.”

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Id. at ¶ 12.

Affidavit of Stella Jones at ¶ 11.

Safety signals may arise from post-marketing data

United States District Court
For the Northern District of California

10

and other sources, and even a single well-documented case report

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can be viewed as a signal.

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reveal the nature of the safety signal.

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further opposition to Plaintiffs’ motion for reconsideration,6

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they state that, in addition to the first case report published in

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February 2005, there were five cases reported to the FDA’s Adverse

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Event Reporting System (AERS) through May 2006, when Centocor

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added the black-box warning to the Remicade label and distributed

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a “Dear Healthcare Provider” letter to physicians.

Id.

Centocor’s submission did not
In Abbott, TEVA and PAR’s

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25
26
27
28

5

The Rosh Report examined ten incidents of hepatosplenic Tcell lymphoma in young patients receiving Remicade in combination
with 6-MP or azathioprine (AZA), the parent compound of 6-MP.
Rosh Report at 2, 6. The Rosh Report cited Centocor data as well
as an FDA “Short Communication” authored by researchers from the
Center for Drug Evaluation and Research, a part of the federal
agency. The Short Communication was published in February 2007 in
the Journal of Pediatric Gastroenterology and Nutrition.
Defendants Abbott, TEVA and Par’s Further Opposition to
Plaintiffs’ Mot. for Reconsideration, Ex. 2.
6

Centocor and Johnson & Johnson, as well as GSK, joined the
arguments made in this opposition brief. Docket Nos. 229 and 230.
9

1

In May 2006, the FDA approved the new use of Remicade for

2

reducing signs and symptoms and inducing and maintaining clinical

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remission in pediatric patients with moderately to severely active

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Crohn’s disease who have had an inadequate response to

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conventional therapy.

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also required the addition of the following black box warning:

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8
9

United States District Court
For the Northern District of California

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Jones Affidavit at ¶ 14.

However, the FDA

RARE POSTMARKETING CASES OF HEPATOSPLENIC T-CELL
LYMPHOMA HAVE BEEN REPORTED IN ADOLESCENT AND YOUNG
ADULT PATIENTS WITH CROHN’S DISEASE TREATED WITH
REMICADE. THIS TYPE OF T-CELL LYMPHOMA HAS A VERY
AGGRESSIVE DISEASE COURSE AND IS USUALLY FATAL. ALL OF
THESE HEPATOSPLENIC T-CELL LYMPHOMAS WITH REMICADE HAVE
OCCURRED IN PATIENTS ON CONCOMITANT TREATMENT WITH
AZATHIOPRINE OR 6-MERCAPTOPURINE.
Haverty Dec., Ex. 3.

12
Dr. Rich testified that he would have received this black box
13
warning in the form of a letter or other notification at about the
14
time it was issued.

Rich Dep. at 214:23-215:3.

15
Also in May 2006, Maxx underwent a colonoscopy that revealed
16
no signs of IBD.

Id. at 198:1-199:14.

According to Dr. Rich, a

17
decision to discontinue Remicade or use an alternative medication
18
would have been made at the time of the colonoscopy, based on the
19
results of the examination.

Id. at 172:10-12.

Maxx received no

20
further infusions of Remicade.
21
As of October 5, 2006, the AERS had received notice of eight
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young patients with Crohn’s Disease and ulcerative colitis who
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received Remicade with concomitant immunosuppressant therapy,
24
including 6-MP in some cases, and developed hepatosplenic T-cell
25
lymphoma.

Abbott, TEVA and Par’s Further Opposition to

26
Plaintiffs’ Mot. for Reconsideration, Ex. 2, FDA Short
27
Communication.
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10

1

By November 2006, Maxx experienced a relapse.

On November

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22, 2006, he received his first prescription for Humira, taking

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the drug in combination with 6-MP.

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testified that he first treated patients with Humira in early 2005

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or 2006 when two sixteen-year-old female patients with IBD

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received the drug.

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a rheumatologist, wrote Maxx’s first prescription for Humira

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because, when Humira was first placed on the Kaiser formulary, it

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was placed under limited release, only through rheumatologists.

Id. at 217:14-16.

Id. at 193:3-7; 173:19-25.

Dr. Rich

Dr. Aileen Dillon,

United States District Court
For the Northern District of California

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Id. at 217:14-218:6.

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prescribing Humira to his patients, he warned them of a “nonzero

12

but increased risk of serious infections and malignancies.”

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at 193:23-194:11.

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literature he had reviewed and discussions he had had with other

15

physicians.

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19
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Dr. Rich testified that when he first began

Id.

His awareness of this risk was based on

Id. at 194:12-18.

When asked why he did not treat Maxx with Remicade in
November 2006, Dr. Rich responded,
So in November ‘06, we had been aware for some time of
complication of hepatosplenic T-cell lymphoma, so that
would have been part of my discussion with the family.
Ease of therapy is always a discussion with Humira
versus Remicade.

21

Id. at 218:13-23.

22

administered by the patient or a family member at home through

23

subcutaneous injections, while Remicade requires a patient to

24

visit a facility for two to three hour infusions.

25

19, 267:5-23.

26

Dr. Rich explained that Humira may be

Id. at 174:15-

When asked whether he opted for Humira because of the black

27
box warning concerning Remicade, Dr. Rich testified, “I think that
28
11

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the concern of hepatosplenic T-cell lymphoma would have been part

2

of my discussion with the family and it would have been part of my

3

thinking about the use of this disease (verbatim).”

4

219:16-22.

5

Humira’s use in combination with 6-MP and hepatosplenic T-cell

6

lymphoma.

Id. at

Dr. Rich did not recall any similar warning regarding

Id. at 219:23-220:2.

Dr. Rich did not state that he

7
would not have prescribed Humira in November 2006, had there been
8
9

a black box warning or similar alert regarding the use of Humira,

United States District Court
For the Northern District of California

10

alone or in combination with 6-MP, and the occurrence of

11

hepatosplenic T-cell lymphoma.

12

testified that Dr. Rich never informed her of the black box

13

warning concerning Remicade, but told her that Humira had a better

14

safety profile, in addition to being easier to administer.

Maxx’s mother, Lisa Wendell,

15
Haverty Dec., Lisa Wendell Dep. at 77:4-13.
16
In deposition, Dr. Rich was asked whether his drug
17
18

recommendation was informed by the fact that Remicade had a black

19

box warning about a rare, aggressive cancer, while Humira did not.

20

Dr. Rich responded,

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I don’t think the black box would have been a primary
driving point in the use of medicine, just as FDA
indication or not is not a driving point, as FDA
doesn’t indicate very much of anything in pediatrics.
Id. at 220:1-15.
Later, Dr. Rich was asked again whether information that he
had about the cases of hepatosplenic T-cell lymphoma associated
with Remicade and 6-MP combination use informed in any way his

27
28
12

1

recommendation that Maxx start Humira in November 2006.

2

answered,

3
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He

The occurrence of hepatosplenic T-cell lymphomas and
the information and knowledge about that would have
been part of many things that would have gone into my
own thinking on how to use this--these medications and
my discussion with the patients on how to use these
medications.
Id. at 225:7-113.
In addressing whether all anti-TNF drugs carry the same

8

risks, Dr. Rich testified that Humira was “entirely humanized,”

9

whereas Remicade was “75 percent humanized and 25 percent mouse.”

United States District Court
For the Northern District of California

10

Id. at 194:24-25.

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counsel,

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Dr. Rich engaged in the following exchange with

A: So I presented [anti-TNF] medications always as
having an increased but nonzero increased risk. And
if I was asked by a patient, “Why do you use one
versus the other,” or why we were considering Humira,
it may have come up in discussions that Humira was
fully humanized and may have--my statement would have
--would have been, “It may have a better safety
profile.”

17

Q: What was the basis of your thinking that it may
have a better safety profile?

18

A: That it was fully humanized.

19

Q: What--

20

A: That there are allergy side effects to these
medicines.

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Q: Okay. Other than allergies, did the fact that
Humira was fully humanized, monoclonal antibody, as
opposed to Remicade, affect, in your mind, the risk of
malignancies?
A: I can’t recall whether I thought that or not. The
fact that there--I’m not an immunologist, and I’m not
sure they can answer that question. But the fact that
there is no mouse suggests that it might have been a
consideration in my thinking, that it’s a possibility.
Id. at 195:13-196:12.

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13

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When asked if he had “an opinion about whether or not Humira

2

had a better safety profile than Remicade for use in combination

3

therapy with 6-MP” with respect to the risk of hepatosplenic T-

4

cell lymphoma, Dr. Rich responded,

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United States District Court
For the Northern District of California

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I don’t believe I had an--an opinion. There was a-had been a thought, as I said, that Remicade may-Humira, excuse me, may have a better safety profile.
And I don’t remember what I thought or didn’t think or
knew about cases in November of ‘06. But I don’t
believe there had been cases reported at that time of
patients with Humira developing hepatosplenic T-cell
lymphoma. So it would have been a possibility in my
mind that it had a better safety profile, and I would
have said that to a patient.
Id. at 226:21-227:7.
Based on Dr. Rich’s recommendation, Maxx took Humira for at

13

least eight months.

14

hepatosplenic T-cell lymphoma.

15

In mid-July 2007, Maxx was diagnosed with
In December 2007, he passed away.

As noted earlier, in February 2007, the FDA published a Short

16

Communication in the Journal of Pediatric Gastroenterology and

17

Nutrition, authored by researchers from the agency’s Center for

18

Drug Evaluation and Research.

19

Further Opposition to Plaintiffs’ Mot. for Reconsideration, Ex. 2.

20

The Short Communication reported that, as of October 5, 2006, the

21

AERS had received notice of eight young patients with Crohn’s

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Disease and ulcerative colitis who received Remicade with

23

concomitant immunosuppressant therapy, including 6-MP in some

24

cases, and developed hepatosplenic T-cell lymphoma.

25
26

Defendants Abbott, TEVA and Par’s

In May 2007, as previously mentioned, the Rosh Report was
published.

It examined ten incidents of hepatosplenic T-cell

27
28
14

1

lymphoma in young patients receiving 6-MP or AZA in combination

2

with Remicade.

3

During 2007 Dr. Rich continued to treat patients using

4

therapies combining anti-TNF drugs with 6-MP, although he could

5

not recall whether the “combination therapy” consisted of 6-MP

6

combined with Remicade or 6-MP combined with Humira or both.

7

Dep. at 208:11-209:5.

8

using “mono-therapy,” treating patients with an anti-TNF drug

9

alone without concomitant use of 6-MP.

Rich

Most likely in 2008, Dr. Rich switched to

Id. at 208:16-17, 288:13-

United States District Court
For the Northern District of California

10

16.

11

Rich’s decision to use monotherapy as opposed to combination

12

therapy.

13

of practitioners, including many pediatric gastroenterologists,

14

use combination therapy, although that is no longer his practice.

15

Id. at 230:12-15.

Maxx’s case played an “important role” in influencing Dr.

Id. at 230:16-20.

Dr. Rich reported that the majority

16

LEGAL STANDARD

17

Summary judgment is properly granted when no genuine and

18

disputed issues of material fact remain, and when, viewing the

19

evidence most favorably to the non-moving party, the movant is

20

clearly entitled to prevail as a matter of law.

21

56.

22

Eisenberg v. Ins. Co. of N. Am., 815 F.2d 1285, 1289 (9th Cir.

23

1987).

24

the party against whom summary judgment is sought.

25

Elec. Indus. Co. v. Zenith Radio Corp., 475 U.S. 574, 587 (1986);

26

Intel Corp. v. Hartford Accident & Indem. Co., 952 F.2d 1551, 1558

27

(9th Cir. 1991).

Fed. R. Civ. P.

Celotex Corp v. Catrett, 477 U.S. 317, 322-23 (1986);

The court must draw all reasonable inferences in favor of

28
15

Matsushita

1

Material facts which would preclude entry of summary judgment

2

are those which, under applicable substantive law, may affect the

3

outcome of the case.

The substantive law will identify which

4

facts are material.

Anderson v. Liberty Lobby, Inc., 477 U.S.

5

242, 248 (1986).

6
7
8
9

DISCUSSION
I. Centocor and Johnson & Johnson’s Motion for Summary Judgment
Under the learned intermediary doctrine, a manufacturer of a
prescription drug is obliged to warn doctors, not patients, of

United States District Court
For the Northern District of California

10

potential side-effects associated with its pharmaceutical

11

products.

12

(1996).

13

to warn if it provides an adequate warning to the physician about

14

any known or reasonably knowable dangerous side effects of a

15

medicine, regardless of whether the warning reaches the patient.

16

Carlin, 13 Cal. 4th at 1116-17.

17

action for failure to warn must prove not only that no warning was

18

provided or that the warning was inadequate, but also that the

19

inadequacy or absence of a warning caused the plaintiff’s injury.

20

Plummer v. Lederle Laboratories, 819 F.2d 349, 358 (2d Cir. 1987)

21

(applying California law).

22

659, 661 (9th Cir. 2004), “a product defect claim based on

23

insufficient warnings cannot survive summary judgment if stronger

24

warnings would not have altered the conduct of the prescribing

25

physician.”

Carlin v. Superior Court, 13 Cal. 4th 1104, 1116

A manufacturer of prescription drugs discharges its duty

A plaintiff asserting causes of

Under Motus v. Pfizer, Inc., 358 F.3d

26

Centocor asserts that it is entitled to summary judgment

27

because its warnings concerning Remicade were adequate in that the

28

labels had long advised of the risk of lymphomas associated with
16

1

the drug.

2

alleged failure to warn of the risk of hepatosplenic T-cell

3

lymphoma, a rare type of lymphoma that is nearly always fatal.

4

Furthermore, pursuant to the parties’ stipulation, the summary

5

judgment motions at this time are to address the issue of

6

proximate causation.

7

of proximate causation, discovery and litigation on other issues,

8

such as the adequacy of the labeling will proceed.

9

correctly note that as a result of the discovery stay they have

However, Plaintiffs’ claim is based on Centocor’s

If the case is not disposed of on the issue

Plaintiffs

United States District Court
For the Northern District of California

10

been unable to depose Dr. Stella Jones, who submitted an affidavit

11

concerning Remicade label changes.

12

uncover what was known to Defendants about lymphomas at the time

13

labels were issued.

14

this point in time, is not a basis for granting summary judgment

15

in favor of Centocor.

16

Thus, they have been unable to

The purported adequacy of the labeling, at

Centocor also argues that Plaintiffs cannot establish

17

proximate causation because Dr. Rich was already aware, as of

18

“late 2005,” of the occurrence of hepatosplenic T-cell lymphoma in

19

adolescent and young adult patients taking Remicade with 6-MP, but

20

he continued to prescribe the medications together.

21

point to medical literature to dispute Dr. Rich’s testimony on

22

this point.

23

learned of the risk of hepatosplenic T-cell lymphoma could support

24

a finding that he did not learn of it until after late 2005,

25

perhaps not until the black box warning in May 2006.

26

stated that he could not remember the exact time and circumstances

27

when he learned of hepatosplenic T-cell lymphoma occurring in

28

young males receiving combination therapy.

Plaintiffs

Dr. Rich’s explanation of the course of events as he

17

Dr. Rich

He testified that in

1

late 2005 he became aware of such cases, plural.

2

that he did not recall if he first learned of the cases at a

3

meeting, but if the cases were reported at a meeting, he was not

4

in attendance.

5

incidents from a case report or abstract, followed by further

6

reporting in an article.

7

as of February 2005, there was only one case report, the Thayu

8

Report, in the medical literature concerning such an incident.

9

Dr. Rich stated

He recalled learning of approximately six

However, the Rosh Report indicates that,

It is not disputed that five additional cases were reported

United States District Court
For the Northern District of California

10

to the FDA through AERS by May 2006.

11

evidence for a jury to infer reasonably that Dr. Rich learned of

12

the five cases before Maxx’s last dose of Remicade in March 2006.

13

Dr. Rich testified that he learned about drug therapies from a

14

variety of sources.

15

information about the AERS-reported cases from any large meetings,

16

conferences and smaller gatherings with colleagues.

17

that he may have learned of two cases from discussions with

18

physicians based in the East Bay and Atlanta.

19

evidently learned of the case from the East Bay physician after

20

Maxx was diagnosed with hepatosplenic T-cell lymphoma and

21

discussed such a case with the physician from Atlanta in the “mid-

22

2000s.”

23

Yet, there is insufficient

However, he did not state that he received

He testified

However, Dr. Rich

It was not until February 2007 and May 2007, respectively,

24

that the FDA Short Communication and the Rosh Report were

25

published.

26

received notice of eight young patients receiving combination

27

therapy who developed hepatosplenic T-cell lymphoma.

28

Report addressed ten such cases.

The Short Communication relayed that the AERS had

The Rosh

Defendants have not pointed to a
18

1

publication earlier than February 2007 discussing the occurrence

2

of hepatosplenic T-cell lymphoma in multiple young patients

3

receiving combination therapy.

4

knowledge is consistent with the February 2007 publication of

5

FDA’s Short Communication, followed by the Rosh Report, published

6

in May 2007.

Dr. Rich’s description of his

In sum, Plaintiffs have pointed to evidence that shows a

8

paucity of published information in 2005 and early 2006 concerning

9

the risk of hepatosplenic T-cell lymphoma for patients receiving

10
United States District Court
For the Northern District of California

7

Remicade and 6-MP concurrently; Dr. Rich’s poor memory as to when

11

he learned of the risk; and the chronology of relevant

12

publications in 2007, which reconciles with his description of how

13

he learned of such cases.

14

raise a material dispute of fact as to whether Dr. Rich was aware

15

of the risk before Maxx’s last dose of Remicade and 6-MP in March

16

2006 and the May 2006 issuance of the black box warning.

17

Thus, the evidence is sufficient to

Centocor seeks summary judgment on the grounds that any

18

failure to warn earlier did not cause harm to Maxx because Dr.

19

Rich was already aware of the risk.

20

evidence from which it can be inferred that Dr. Rich learned of

21

the risk no earlier than May 2006, there is a material dispute of

22

fact as to whether Dr. Rich knew of the risk in late 2005.

However, because of the

23

Moreover, there is evidence indicating that, had Dr. Rich

24

known earlier of the risk of hepatosplenic T-cell lymphoma, he

25

would have decided against prescribing Remicade in combination

26

with 6-MP.

27

his awareness of the risk of hepatosplenic T-cell lymphoma in

28

connection with Remicade and 6-MP influenced his decision to

Dr. Rich’s testimony could be understood to imply that

19

1

prescribe Humira, rather than Remicade, when Maxx experienced a

2

relapse in November 2006.

3

monotherapy only, after Maxx developed hepatosplenic T-cell

4

lymphoma while receiving combination therapy and after Dr. Rich

5

learned of the reports of the disease in young patients receiving

6

combination therapy.

7

an earlier warning of the risk would have influenced Dr. Rich to

8

change his prescribed treatment for Maxx.

9

Further, Dr. Rich now prescribes

This raises a question of fact as to whether

This case is distinguishable from Plummer.

In Plummer, the

United States District Court
For the Northern District of California

10

Second Circuit, applying California law, found that judgment

11

should have been entered for the defendant, because the physician

12

knew of the risk for which the plaintiff sought a warning.

13

court concluded that “no harm could have been caused by failure to

14

warn of a risk already known.”

15

Plummer, there is a dispute of fact as to whether Dr. Rich already

16

knew of the risk of hepatosplenic T-cell lymphoma associated with

17

Remicade and 6-MP at the time the black box warning was issued.

18

This case is also distinguishable from Motus, where the treating

19

physician testified unequivocally that he neglected to read the

20

published warnings and did not rely on information from the drug

21

representatives before prescribing the medication that allegedly

22

induced the decedent to commit suicide.

23
24
25

819 F.2d at 359.

The

In contrast to

385 F.3d at 661.

Summary judgment in favor of Centocor for lack of evidence of
proximate causation is unwarranted.
Johnson and Johnson, Centocor’s parent company, moves for

26

summary judgment on the grounds that it has not been involved in

27

the research, development, marketing or manufacture of Remicade,

28

and that it has not controlled or dominated the activities of
20

1

Centocor to an extent that could give rise to parental liability

2

for failure to warn.

3

Johnson has submitted a declaration by its Assistant Secretary,

4

Lacey Elberg, executed on August 30, 2011.

5

that they have been unable to conduct discovery to explore the

6

facts attested to by Ms. Elberg.

7

corporation is not liable for the acts of its subsidiaries, an

8

exception may apply where the corporate veil may be pierced

9

because “the corporate form would otherwise be misused to

In support of these contentions, Johnson and

Plaintiffs respond

Although in general a parent

United States District Court
For the Northern District of California

10

accomplish certain wrongful purposes.”

11

Bestfoods, 524 U.S. 51, 61-62 (1998).

12

has been stayed since June 23, 2011, pursuant to the parties’

13

stipulation.

14

their mediation or the resolution of their motions for summary

15

judgment, whichever occurred later.

16

further discovery would be scheduled in the event that the case

17

continued.

18

judgment is premature and the Court denies it without prejudice.

19

II. Motion for Reconsideration

20

United States v.
Discovery in this matter

The parties agreed to stay discovery until after

The parties stipulated that

Thus, Johnson and Johnson’s motion for summary

As noted earlier, Plaintiffs move for reconsideration of the

21

Court’s prior order, granting summary judgment in favor of Abbott,

22

TEVA, PAR and GSK, finding insufficient evidence of proximate

23

causation with respect to Humira and 6-MP, based on the learned

24

intermediary doctrine.

25

A district court may reconsider its grant of summary judgment

26

under Federal Rule of Civil Procedure 59(e).

27

Multnomah County, Or. v. ACandS, Inc., 5 F.3d 1255, 1262 (9th Cir.

28

1993).
21

Sch. Dist. No. 1J,

1

Plaintiffs rely on the evidence discussed above, casting

2

doubt on Dr. Rich’s testimony that he was aware of the risk of

3

hepatosplenic T-cell lymphoma in late 2005, as well as testimony

4

by Dr. Rich that the Court did not discuss in its December 15,

5

2011 order.

6

benefit of the Rosh Report, indicating that, as of February 2005,

7

only one case report of hepatosplenic T-cell lymphoma had been

8

published, and revealing the chronology of the medical

9

publications on the risk of hepatosplenic T-cell lymphoma in

Specifically, the Court previously did not have the

United States District Court
For the Northern District of California

10

combination therapy.

11

take full account of the ambiguities in Dr. Rich’s testimony and

12

the vagueness of his memory as to when he learned of the risk of

13

hepatosplenic T-cell lymphoma.

14

15, 2011 order to ensure that it is supported in light of the full

15

record of evidence concerning causation in connection with the

16

three drugs at issue in this case.

17

GSK, TEVA and PAR to escape the impact of certain evidence because

18

it was only submitted in connection with Centocor and Johnson and

19

Johnson’s later motion for summary judgment.

20

issue inconsistent rulings simply because Defendants decided to

21

move for summary judgment at different times.

22

Court reconsiders the merits of Abbott’s, TEVA’s, PAR’s and GSK’s

23

motions for summary judgment.

24

Furthermore, the Court’s prior order did not

The Court reconsiders its December

It would be unfair for Abbott,

The Court will not

Accordingly, the

Docket Nos. 177, 179, 183 and 185.

Those Defendants moved for summary judgment on the grounds

25

that Dr. Rich was aware early on of the risk of hepatosplenic T-

26

cell lymphoma in adolescent and young adult patients taking

27

Remicade with 6-MP.

28

knew, as of late 2005, of the risk posed by Remicade in

They relied on Dr. Rich’s testimony that he

22

1

combination with immunosuppressants like 6-MP for young patients

2

and that he considered those risks applicable to other TNF-

3

blockers, such as Humira.

4

is sufficient evidence to create a material dispute of fact as to

5

whether Dr. Rich, in fact, knew about the risk in late 2005.

6

For the reasons explained above, there

Abbott, TEVA and PAR argue that the newly considered evidence

7

is not sufficient to change the outcome.

8

Rosh Report establishes that the first case report was published

9

in February 2005 and an additional five cases were reported to the

They contend that the

United States District Court
For the Northern District of California

10

FDA’s AERS through May 2006.

11

Rich’s testimony that he knew of the risk in late 2005, and that

12

there is nothing to contradict it.

13

indicating that Dr. Rich was apprised of cases of hepatosplenic T-

14

cell lymphoma in young patients receiving concomitant Remicade and

15

immunosuppressive therapy at the same time that they were being

16

reported to AERS.

17

learned of these cases through the medical literature and the FDA

18

black box warning.

19

learned of two different cases from a colleague in the East Bay

20

and a colleague from Atlanta, he did not recall that those

21

conversations occurred before Maxx’s diagnosis with hepatosplenic

22

T-cell lymphoma.

23

adjudication that Dr. Rich learned of multiple cases of

24

hepatosplenic T-cell lymphoma in late 2005 and therefore that a

25

failure to warn of the risk did not cause Maxx harm.

They contend that this verifies Dr.

However, there is no evidence

Instead, the evidence indicates that Dr. Rich

When Dr. Rich testified that he may have

Thus, the evidence does not require summary

26

Abbott, TEVA and PAR also argue that Plaintiffs cannot

27

satisfy their burden to produce evidence of causation by simply

28

challenging Dr. Rich’s credibility as to when he learned about the
23

1

risk.

2

decision not to ask Dr. Rich directly whether a different warning

3

would have caused him not to prescribe Humira or 6-MP.

4

Plaintiffs are not limited to proving causation by relying on

5

direct evidence.

6

comprising Dr. Rich’s course of conduct.

7

could support a jury finding that he did not learn of the risk of

8

hepatosplenic T-cell lymphoma caused by combining Remicade and 6-

9

MP in late 2005 but rather only in May 2006.

Defendants contend that Plaintiffs made a strategic

However,

Rather, they rely on circumstantial evidence
Dr. Rich’s testimony

Thereafter, he

United States District Court
For the Northern District of California

10

informed the Plaintiffs that Humira offered a better safety

11

profile than Remicade and began prescribing Humira to Maxx on his

12

relapse in November 2006.

13

also rely on other testimony by Dr. Rich reasonably to infer that

14

his knowledge of the risk influenced his decision to prescribe

15

Humira, rather than Remicade, when Maxx relapsed in November 2006.

16

Specifically, Dr. Rich testified that his awareness in November

17

2006 of the risk of hepatosplenic T-cell lymphoma in connection

18

with Remicade and 6-MP informed his thinking about how to

19

prescribe the medications.

20

knowledge of such a risk in connection with Humira would have

21

informed his treatment decision as to combination therapy with

22

that drug as well.

If a jury made such a finding, it could

Accordingly, a jury could infer that

23

Plaintiffs have demonstrated that the Court’s reconsideration

24

of its prior ruling is warranted and they have produced sufficient

25

evidence to raise a dispute of fact as to causation with respect

26

to Humira and 6-MP.

27

judgment in favor of Abbott, TEVA and PAR is withdrawn and their

28

motions are denied.

The Court’s prior order granting summary

24

1

GSK submitted an opposition to Plaintiffs’ motion for

2

reconsideration separate from that submitted by Abbott, TEVA and

3

PAR.

4

three Defendants, but also argued that Plaintiffs cannot dispute

5

that it ceased distribution of its 6-MP product, marketed as

6

Purinethol, and sold its distribution rights for the product on

7

July 1, 2003, before the risk of hepatosplenic T-cell lymphoma

8

associated with 6-MP was reasonably scientifically knowable.

9

In its opposition GSK adopted the arguments made by the

GSK first raised this issue in its March 2, 2011 motion for

United States District Court
For the Northern District of California

10

summary judgment.

11

was premature because further discovery was required to address

12

the motion.

13

prejudice to allow for more discovery.

14

Plaintiff opposed the motion arguing that it

On April 19, 2011, Court denied the motion without

GSK raised the issue again in a footnote in its second motion

15

for summary judgment, which otherwise relied on the issue of

16

proximate causation.

17

look back at its March 2, 2011 motion for summary judgment and

18

decide the merits of the issue.

19

request without the need for filing a further opposition to the

20

motion.

21

consideration.

22

At the hearing, GSK requested that the Court

Plaintiffs have agreed to this

Therefore, the Court deems the motion resubmitted for

Plaintiffs have not disputed that there were no reports to

23

AERS of hepatosplenic T-cell lymphoma associated with the use of

24

Purinethol before July 1, 2003 and no such reports were published

25

in medical or scientific literature by that date.

26

only that the case report authored by M. Thayu and other

27

researchers and published in February 2005 was received by the

28
25

Plaintiffs note

1

journal for publication on May 18, 2003 and accepted for

2

publication on October 15, 2004.
To succeed on their strict liability claim against GSK,

4

Plaintiffs must produce evidence in support of its duty to warn.

5

“Drug manufacturers need only warn of risks that are actually

6

known or reasonably scientifically knowable.”

7

at 1117 (emphasis in original).

8

occurrence of hepatosplenic T-cell lymphoma in connection with

9

Purinethol was known by the authors of the case report before July

10
United States District Court
For the Northern District of California

3

1, 2003, Plaintiffs have not presented evidence that the risk was

11

actually known or should have been known by the scientific or

12

medical communities of which GSK is a part.

13

information concerning the occurrence of hepatosplenic T-cell

14

lymphoma in connection with Purinethol was not reported to AERS or

15

discussed in the medical literature until after GSK ceased to

16

distribute the drug.

17

required to warn of every conceivable adverse reaction.

18

at 1114-15 (noting that FDA regulations are relevant in a common

19

law action for failure to warn and that a defendant could present

20

evidence that, consistent with FDA regulations, it was not

21

permitted to warn of the adverse effect because it was too

22

speculative).

23

failure to warn of the risk of hepatosplenic T-cell lymphoma

24

associated with Purinethol.

25

Carlin, 13 Cal. 4th

Although, necessarily, one

GSK is correct that

Furthermore, drug manufacturers are not
See id.

Thus, GSK cannot be held strictly liable for

Likewise, Plaintiffs’ negligence claim requires them to prove

26

that GSK “did not warn of a particular risk for reasons that fell

27

below the acceptable standard of care; i.e., what a reasonably

28

prudent manufacturer would have known and warned about.”
26

Id. at

1

1112.

2

indicating that a reasonable manufacturer would have been in a

3

position to discover the case that Thayu and her co-authors

4

reported, prior to July 1, 2003.

5

on their negligence claim against GSK.

6
7

Plaintiffs have presented no evidence, expert or otherwise,

Thus, Plaintiffs cannot prevail

GSK’s motion for summary judgment on Plaintiffs’ claims
against it is granted.

8

CONCLUSION

9

The Court denies Centocor and Johnson and Johnson’s joint

United States District Court
For the Northern District of California

10

motion for summary judgment.

11

Plaintiffs’ motion for reconsideration.

12

Court’s December 15, 2011 order is withdrawn and Abbott’s, TEVA’s

13

and PAR’s motions for summary judgment based on the learned

14

intermediary doctrine are denied.

15

However, summary judgment in favor of GSK is granted on the

16

grounds that there is insufficient evidence for a reasonable jury

17

to find that, before July 1, 2003 when it discontinued

18

distribution of Purinethol, it had a duty to warn of the risk of

19

hepatosplenic T-cell lymphoma, as it argued in its March 2, 2011

20

motion.

21

case management conference on August 8, 2012 at 2:00 pm, and shall

22

submit a joint case management statement one week prior to the

23

conference.

24

Docket No. 179.

Docket No. 205.

The Court grants

Docket No. 220.

The

Docket Nos. 177, 183 and 185.

The remaining parties shall appear for a

IT IS SO ORDERED.

25
26
27

Dated:

CLAUDIA WILKEN
United States District Judge

28
27