Porter v. Tap Pharmaceutical, et al

Filing 583

Judge Richard G. Stearns: ORDER entered. MEMORANDUM acknowledging David Mazzone Second Annual Research Awards progress and Accounting Report #5(Zierk, Marsha)

UNITED STATES DISTRICT COURT
DISTRICT OF MASSACHUSETTS
M.D.L. NO. 1430
CIVIL ACTION NO. 01-10861
IN RE LUPRON® MARKETING AND
SALES PRACTICES LITIGATION
MEMORANDUM ACKNOWLEDGING THE RECEIPT AND
REVIEW OF THE A. DAVID MAZZONE SECOND ANNUAL RESEARCH
AWARDS PROGRESS and ACCOUNTING REPORT #5
December 18, 2013
STEARNS, DJ.
On October 8, 2013, Dr. Philip Kantoff of the Dana-Farber/Harvard
Cancer Center (DF/HCC), the principal investigator for the A. David
Mazzone Research Awards Program, and co-principal investigator, Dr.
Jonathan Simon, President of the Prostate Cancer Foundation (PCF),
submitted Progress and Accounting Report #5 for the court’s review. The
Report covers the period from August of 2012 to July of 2013. As the
Report notes, the Mazzone Awards Program is now in its third year and
currently supports the work of 93 investigators involved in twenty-seven
separate prostate cancer research projects. Twenty-three of these projects
are funded through DF/HCC and four through PCF Challenge Awards.
Nine new projects were undertaken in 2013 through DF/HCC and one
through PCF. The Report summarizes the scientific progress and financial
accountings for the twenty-eight active projects and the DF/HCC Post-Bacc
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training (CURE) award funded through the Mazzone Research Program
during the reporting year.1, 2
In the 2013 cycle, the scientific review committee established
through DF/HCC received and peer reviewed 50 proposals from 48
institutions involving 163 researchers. It awarded nine grants involving 36
researchers from eleven institutions. PCF received and peer reviewed 62
proposals and awarded one grant which involves eight researchers. In July
of 2013, the initial DF/HCC and PCF award recipients completed their
second year of research, while the 2012 award recipients finished their first
full year of research.

Each of the award recipients has submitted the

required scientific progress and financial reports for review by Dr. Kantoff
and the Program’s Science Advisory Board. As the Program matures, it has
begun to show solid scientific accomplishments. The court has taken the
following examples from Dr. Kantoff’s extensive Report.

The Report notes that Career Development grantee Dr. Kathryn
Wilson (phosphorus and calcium intake, tumor microenvironment and
prostate cancer progression), received an extension of her grant to October
23, 2013, and for this period has submitted a partial progress report.
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Diseases and Conditions grantee Dr. Jose Teixeira
(preclinical in vivo studies investigating the efficacy of mTOR inhibitors for
uterine fibroids) relocated during the reporting period to Michigan State
University but will continue to collaborate on the in vivo studies project.
Dr. Aaron Styer (Massachusetts General Hospital) replaced Dr. Teixeira as
the principal investigator on June 1, 2013. Dr. Styer’s progress and
accounting reports will be reviewed for the next annual submission to the
court.  
2

  Lupron-Treatable

2 

(1)

Career Development Principal Investigator David Miyamoto

(Massachusetts General Hospital) published as lead author the article:
Androgen receptor signaling in circulating tumor cells as a marker of
hormonally responsive prostate cancer, Cancer Discovery, 2:995-1003
(2012).

The

article

describes

the

development

of

a

single

cell

immunofluorescence-based assay for measurement of androgen receptor
(AR) activity, and explores the feasibility of measuring AR activity in
circulating tumor cells as a biomarker to monitor and predict responses to
second line hormonal therapy in CRPC.
(2)

Disparities Research Principal Investigator Nancy Keating

(Harvard Medical School) co-authored the article: Explaining racial
differences in prostate cancer mortality, Cancer Sept. 2012 1;118(17):42809. The article explores the reasons for a higher incidence of prostate cancer
mortality among black males and low-income males, and the palliative
effects of more frequent PSA screening, aggressive treatment approaches,
and greater vitamin D intake.
(3)

High Impact Principal Investigator Levi Garraway (Dana--

Farber Cancer Institute) utilized a prostate cancer cell model (LNCaP) that
requires androgen for survival to perform genome scale small-hairpin RNA
(shRNA) screens to identify genes whose silencing (loss-of-function) allow
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cells to proliferate in the absence of androgen, as well as in the presence of
enzalutamide (MDV3100), a drug that interferes with the function of the
androgen receptor. Among other genes, Dr. Garraway and his colleagues
identified two regulatory subunits of a large enzymatic complex operant in
the cell, the loss of which enables LNCaP cells to grow despite the lack of
androgen. This enzymatic complex (PP2A) regulates signaling pathways
active in the prostate cancer cell, pathways that implicate many factors,
some of which could potentially be targetable with existing drugs.
(4)

To further define the AR cistrome in actual tissue, High Impact

Principal Investigator Matthew Freedman (Dana-Farber Cancer Institute),
with his coworkers, developed a working method to perform AR chromatin
immunoprecipiation (ChIP) in human prostate tissue. Given the likely
importance of enhancer binding sites, Dr. Freedman and his team reasoned
that obtaining data outside of cell lines would be important to: (a) compare
the AR cistrome in cell lines versus human tissue; and (b) provide a more
comprehensive catalog of the AR sites across multiple individuals (as
opposed to in only a few cell lines). Thus far, their data reveals that there
are tens of thousands of AR sites that exist in human tissue that are not
present in the LNCaP cell line.
(5)

Investigator Glenn Liu (University of Wisconsin) reported a
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strong clinical effort to determine, by PET ICT imaging, the total burden of
cancer in patients with metastatic prostate cancer. Early results
demonstrate a concordance of imaging results at multiple centers. A
multicenter protocol has been developed to validate this imaging modality
as a biomarker for response to therapies for metastatic prostate cancer. If
successful, this imaging biomarker will greatly reduce the complexity of
clinical trials that are dependent on the endpoint of overall survival and will
shorten the time and cost for determining the efficacy of new treatments.
(6)

Investigator William Nelson (Johns Hopkins Medicine) is

conducting an epigenetics study of chemical modification of DNA that
control the expression of genes.

His research has demonstrated that

blocking certain epigenetic alterations with an FDA 12 approved medication
such as Vidaza sensitizes treatment-resistant prostate cancer cells to a
variety of therapies. Clinical trials in advanced prostate cancer patients are
planned based on these findings and will be funded by resources that
leverage this Mazzone-PCF Challenge Award.
(7)

Principal

Investigator

Martin

Pomper

(Johns

Hopkins

Medicine), with others, successfully created a gene therapy approach that
causes the expression of a new receptor on the surface of prostate cancer
cells. Infusion of a binding partner to this receptor combined with either a
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lethal radioactive payload or a molecular imaging tracer allows
simultaneous detection and killing of metastatic prostate cancer. This
approach has created what is termed a theranostic, enabling simultaneous
detection and killing of prostate cancer.
(8)

Bert O’Malley (Baylor College of Medicine) is examining the

engine of prostate cancer - the androgen receptor molecule. AR combines
with a complex set of proteins that ultimately bind specific regions of the
cancer cell genome and drive the progression and survival of the disease.
Dr. O’Malley reports that his group is exploring experimental medicines
that will disrupt the AR regulatory complex, possibly leading to a new
treatment modality for metastatic prostate cancer.
CONCLUSION
The court appreciates the thoroughness of the Report submitted by
Dr. Kantoff and Dr. Simons and congratulates the Mazzone research award
recipients for their ongoing achievements. The court looks forward to the
receipt of Annual Report #6 on or before March 30, 2014.

/s/Hon. Richard G. Steams
______________________________

United States District Judge

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