July 28, 2016
MEMORANDUM AND ORDER ON DEFENDANTS' MOTION FOR
SUMMARY JUDGMENT AND PLAINTIFF'S MOTION TO AMEND SECOND
B. Krupp, Justice
Gerald Gentile (" plaintiff') has sued defendants
Biogen Idec, Inc. (" Biogen") and Elan
Pharmaceuticals, Inc. (" Elan") (collectively
" defendants") to recover for injuries his wife,
Diane Gentile (" Mrs. Gentile"), suffered after
taking defendants' drug, Tysabri (" Tysabri").
The case is before me on defendants' motion for summary
judgment and plaintiff's motion to amend his Second
Amended Complaint. For the following reasons, defendants'
motion for summary judgment is ALLOWED and
plaintiff's motion to amend is DENIED .
summary judgment record, viewed in the light most favorable
to plaintiff, contains the following facts material to this
1981, Mrs. Gentile was diagnosed with multiple sclerosis
(" MS"). MS is a chronic, progressive, disabling
autoimmune disease of the central nervous system. It can lead
to brain atrophy and cognitive impairment, confine an
individual to a wheelchair or bed, and result in death. MS
has no known cure.
2004, the United States Food and Drug Administration ("
FDA") first approved the prescription drug Tysabri for
the treatment of relapsing forms of MS. Tysabri is intended
to decrease the number of MS relapses and reduce and delay
nerve damage and resulting disability.
collaborated on aspects of research, development and
commercialization of Tysabri. Biogen, a Delaware corporation
with its headquarters in Massachusetts, manufactured the drug
and held the FDA license and regulatory responsibilities
associated with it. Elan, a Delaware corporation with a
principal place of business in California, distributed the
drug and also marketed it to treat Crohn's disease.
February 2005, defendants received reports that two patients
involved in clinical trials of Tysabri, who also concurrently
used Avonex, another MS medication, developed progressive
multifocal leukoencephalopathy (" PML"). PML is a
rare viral brain infection caused by the John Cunningham
virus (" JCV"). A significant portion of the adult
population has been exposed to JCV, which is typically
February 28, 2005, following the reports of the PML cases,
Biogen withdrew Tysabri from the market and suspended its
clinical trials. Defendants attempted to better
understand and quantify the risk of PML. In March 2006, an
FDA advisory panel considered Biogen's proposal to put
Tysabri back on the market. On June 5, 2006, the FDA approved
returning Tysabri to the market, subject to conditions and
requirements to address the PML risk. One of these conditions
required that Tysabri only be prescribed in accordance with a
mandatory risk evaluation and management strategy program,
also known as the Tysabri Outreach: Unified Commitment to
Health (" TOUCH") Program. The TOUCH Program was
intended " to assess the risk of [PML] associated with
[Tysabri], minimize the risk of PML, minimize death and
disability due to PML, and promote informed risk-benefit
decisions regarding TYSABRI® use."
TOUCH Program required, among other things: (1) prior to
prescribing Tysabri, a physician must acknowledge, in
writing, that the physician understands the PML risk and must
obtain a written acknowledgment of the risk from the patient;
(2) prior to each Tysabri infusion, a specially trained nurse
must confirm that the patient has read the Medication Guide
that includes the PML warnings; and (3) the nurse must also
question the patient about the patient's understanding of
the PML risk and any new symptoms that could be early signs
condition for the reintroduction of Tysabri to the market was
the requirement of a " black box" warning to inform
prescribers that Tysabri use increases a patient's risk
of developing PML. The black box warning stated, in part:
[PML], an opportunistic infection caused by the JC virus that
typically occurs in patients that are immunocompromised, has
occurred in 3 patients who received TYSABRI® in clinical
trials (see BOXED WARNING). Two cases of PML were observed in
1869 patients with multiple sclerosis treated for a median of
120 weeks. The third case occurred among 1043 patients with
Crohn's disease after the patient received 8 doses. The
absolute risk for PML in patients treated with TYSABRI®
cannot be precisely estimated, and factors that might
increase an individual patient's risk for PML have not
been identified. There are no known interventions that can
reliably prevent PML or adequately treat PML if it occurs. It
is not known whether early detection of PML and
discontinuation of TYSABRI® will mitigate the disease.
There is limited experience beyond 2 years of treatment. The
relationship between the risk of PML and the duration of
treatment is unknown.
All three cases of PML occurred in patients who were
concomitantly exposed to immunomodulators . . . or were
immunocomprised due to recent treatment with
immunosuppressants . . . Ordinarily, therefore, patients
receiving chronic immunosuppressant or immunomodulatory
therapy or who have systemic medical conditions resulting in
significantly compromised immune system function should not
be treated with TYSABRI® . However, the number of cases
is too few and the number of patients treated too small to
reliably conclude that the risk of PML is lower in patients
treated with TYSABRI® alone than in patients who are
receiving other drugs that decrease immune function or who
are otherwise immunocompromised.
warnings also provided in the " Indications and
Usage" section that " TYSABRI® increases the
risk of [PML], an opportunistic viral infection of the brain
that usually leads to death or severe disability ( see
BOXED WARNING AND WARNINGS, [ PML ])."
(Bold in original). Defendants also included this warning in
Tysabri's Medication Guide, which was provided to
patients prior to enrolling in the TOUCH Program. The
Medication Guide also stated that " PML usually happens
in people with weakened immune systems. No one can predict
who will get PML. There is no known treatment, prevention, or
cure for PML."
early March 2006, in response to FDA's request, Biogen
submitted a report on the results of antibody testing
conducted on available serum samples of patients who
participated in the Tysabri clinical trials. The report
concluded " there is no consensus on a clinically
relevant cut off for the ELISA assay or JCV antibody
detection." Biogen continued to research the
significance of the presence of JCV antibodies on the risk of
Gentile resided in New York. In November 2006, Mrs.
Gentile's doctor, Bianca Weinstock-Guttman, M.D. ("
Dr. Guttman"), an MS specialist at the Jacobs
Neurological Institute in Buffalo, New York, prescribed
Tysabri for Mrs. Gentile. Before doing so, Dr. Guttman
performed a JCV DNA test looking for JCV in Mrs.
Gentile's bloodstream. Mrs. Gentile tested negative.
Also, in accordance with FDA requirements, Mrs. Gentile
signed the TOUCH enrolhnent forms, which warned against PML,
and acknowledged that " [m]y chance of getting PML may
be higher if I am treated with other medicines that can
weaken my immune system, including other MS treatments"
and that " [i]t is also not known if treatment for a
long period of time with TYSABRI can increase my chance for
time she prescribed Tysabri to Mrs. Gentile, Dr. Guttman was
familiar with the prescribing information that was in effect,
was enrolled as a TOUCH prescriber, was aware of the PML
risks provided in the Tysabri warnings, understood the
significance of black box warnings, and understood that JCV
could cause PML. When Dr. Guttman prescribed Tysabri to Mrs.
Gentile, the Tysabri warning indicated that " the
relationship between the risk of PML and the duration of
treatment is unknown."
Gentile received her first Tysabri infusion in January 2007.
The label in effect at the time included the provision:
" TYSABRI® increases the risk of [PML], an
opportunistic viral infection of the brain that usually leads
to death or severe disability." The Tysabri infusions
were effective in stabilizing Mrs. Gentile's condition
before she developed PML.
2008, the first two Tysabri-associated PML cases were
confirmed following Tysabri's re-introduction to the
market. After these reports, in August 2008, the FDA approved
Biogen's request to update the label to include the
following: " There is limited experience beyond two
years of treatment. The relationship between the risk of PML
and the duration of treatment is unknown, but most cases of
PML were in patients who received more than one year of
treatment." By July 24, 2009, eleven cases of
Tysabri-associated PML had been confirmed since Tysabri was
reintroduced to the market three years earlier.
September 2009, Mrs. Gentile received her final Tysabri
infusion, her thirty-third monthly infusion since January
2007. In October 2009, Mrs. Gentile was diagnosed with PML.
Hers was the twenty-third confirmed case of PML after
Tysabri's re-approval. Mrs. Gentile died on December 15,
2009, Biogen developed an assay that could reliably detect
JCV antibodies in the blood stream, indicating prior exposure
to JCV. On December 9, 2009, an advisory board of MS and
regulatory experts concluded, however, that data on the JCV
antibody assay " was too preliminary to be of predictive
November 2009, FDA approved Biogen's request to update
Tysabri's label so that it included more details about
the increased risks of PML with longer Tysabri treatment
duration. In July 2010, FDA approved an update to the label
that added warnings about a correlation between a
patient's prior immunosuppressant treatments and PML.
September 8, 2010, FDA rejected Biogen's proposal to add
information to the Tysabri label regarding the significance
of the JCV antibody status, concluding that " the
Division does not believe that there is currently sufficient
information to support the clinical ...