Precision Medicine: Dx leads to Rx - Quest Diagnostics
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5/5/2021 Precision Medicine: Dx leads to Rx
Precision Medicine: Dx leads
to Rx
https://www.thejournalofprecisionmedicine.com/the-journal-of-precision-medicine/precision-medicine-dx-leads-to-rx/ 1/19
5/5/2021 Precision Medicine: Dx leads to Rx
by Mridula Iyer, PhD and Yuri Fesko, MD,
Quest Diagnostics, Secaucus, NJ
The right medicine for the right patient,
that’s the principle behind the Precision
Medicine Initiative, originally focused on
leveraging global investments in cancer
and genome sequencing (superseded by
All of US). More recently, the approach has
grown to encompass the concept of a
more individualized (n of 1) care strategy
for cardiovascular diseases, autoimmune
diseases, cancers, and gene‑centered
maladies, as seen in Figure 1.1
An example of this “n of 1” treatment is
the emerging chimeric antigen receptors
T-cell (CAR-T) therapies, which are
designed specifically for each patient.
Each CAR-T therapy is best designed to
attack the unique disease of a single
patient, thereby improving survival rates.
While these therapies are a more
expensive treatment option, the higher
likelihood for patient response and better
outcomes would result in net overall
improved benefits – e.g., fewer return trips
for treatments, extended lifetime,
improved quality of life for the patient and
his/her family.
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5/5/2021 Precision Medicine: Dx leads to Rx
Precision in prevention: Going further
to identify the right patients
To date, the biggest investment of
precision medicine has been in oncology,
with significant funding committed to
validate biomarkers that test for patients
who can benefit from the most
appropriate treatment.2 However, there is
growing interest in applying precision
medicine to neuromuscular diseases and
some rare diseases, which gives hope to
patients who have typically been
underserved.
In addition to identifying a ected
individuals, a shi is underway towards a
three-fold treatment strategy that includes
early diagnosis, the application of
preventive medicine, and targeted therapy
for precise treatment options. Deeper
understanding of biomarkers and better
understanding of disease causation is
anticipated to improve the ability to
identify populations of at-risk patients
who could benefit from the new therapy3
prior to full disease onset, and hence
evolve into ‘precision in prevention.’4
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5/5/2021 Precision Medicine: Dx leads to Rx
Using robust diagnostic testing strategies
for the detection of eligible, at-risk
patients for preventive care has enormous
benefits and the potential to reduce
overall healthcare costs.
The crucial role of diagnostics,
informatics, and data in a centralized
model
As the focus shi s towards this three-fold
treatment strategy, national reference labs
such as Quest Diagnostics bring a depth of
data, medical and scientific expertise, and
analytics capabilities by centralizing
resources that can:
1. Enable the correlation
between diagnostic insights
with other data sets:
2. Bring together physicians,
patients, and Principal
Investigators (PIs) to drive
more e ective and e icient
clinical trials.
Quest leverages its expertise in informatics
and data to deliver the powerful benefits
of precision medicine to compile and track
patterns for interpreting real-world results
that determine inclusion-exclusion
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criteria, patient engagement, and foster
patient education and awareness.
Technology factors critical to a
centralized model utilizing the
three‑fold treatment strategy
1. Access to critical patient and
physician data
◆ Quest has access to
hundreds of thousands of
patients through nationwide
Patient Service Centers (PSC,
now expanded into Walmart
locations and grocery stores)
and mobile Phlebotomy
services that support patients
who prefer home or o ice
draws.
◆ Quest also has decades of
real-world experience with
physicians: their ordering
behavior, testing practices,
barriers, and typical
preferences in treating
patients. Ensuring that tests
are integrated into these
patterns is o en critical for
success and serve as
guidance for assay design.
◆ Broad access to patients
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and physicians allows Quest
to commercialize tests
e ectively, utilizing a sales
team with expertise in all
therapeutic areas to drive
maximum awareness to
practices, hospitals, patients,
and communities.
2. High-quality tests
◆ Diagnostic tests and
related data and information
provide a quantitative
measure of a patient’s status
of su icient quality for
healthcare providers to make
decisions for treatment.
Qualified reference labs will
validate tests under CAP/CLIA
laboratory guidelines using
the best‑available
technology and
methodology. The data
should be of such quality that
patients are confident in they
will receive the most
appropriate treatment
protocols.
◆ Physician decisions are
based on combination of
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clinical observation, patient
history, and related tests that
serve as guidance for
treatment. For example,
other relevant tests for
biomarkers based on, e.g.,
guidelines for cancer
patients, cholesterol,
potassium levels for cardiac
CDx tests, biomarker testing,
may need to be considered as
part of a patient’s history
from prior tests.
3. Technology expertise and knowledge
across all therapeutic areas
◆ In general, qualified
diagnostics companies
employ the best-available
technology for assay design
across therapeutic areas.
◆ In addition to sensitivity
and specificity, robustness of
the technology is
instrumental in bringing
e ective treatments to
market, especially for
genetically inherited rare
diseases.
◆ Company subject matter
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experts and users (e.g., MDs
and Lab Directors) are
consulted for input on new
assay targets, new assay
designs, and applying their
collective clinical and
medical expertise in
interpreting tests. These
experienced experts add a
personalized component to
this precision approach.
◆ Diagnostics companies
with global reach (like Quest)
o er end-to-end services to
pharmaceutical companies
including the development of
new assays, securing FDA
approval, and launching
tests commercially. Quest, as
a covered entity under HIPAA,
can reach out globally to
partners and to patients for
clinical trial purposes as a
care option.
Successful applications of the precision
medicine-focused model
Supported by program managers assigned
to handle day-to-day activities, projects
are custom designed to meet the
company’s unique goals. Two studies
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highlight the distinctive way Quest
advances the benefits of precision
medicine, customizing each case aligned
with a general format:
◆ Develop a new test → FDA
approval →
commercialization
◆ Develop a new test →
commercialization
◆ Existing LDT on menu →
FDA approval →
commercialization
◆ Existing LDT on menu →
commercialization
Case study #1: STRATIFY JCV test for
Tysabri
Overall process followed for this case:
Develop a new test → seek FDA approval →
go to commercialization
Quest Diagnostics was granted a de novo
classification petition to its STRATIFY JCV™
Antibody ELISA testing service.5
Developed under exclusive collaboration
with Biogen Idec and o ered only through
Quest Diagnostics, STRATIFY JCV is the
first blood test to receive FDA marketing
authorization for the qualitative detection
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of antibodies against the John
Cunningham virus (JCV). STRATIFY JCV
provides a surrogate measure of the load
of this polyomavirus for stratifying risk for
progressive multifocal
leukoencephalopathy (PML), an infrequent
but serious brain infection. TYSABRI®
(natalizumab*) is a highly e ective therapy
for patients at-risk for relapsing forms of
MS.
Quest Diagnostics supported the Tysabri
project by:
◆ Developing the assay;
◆ Performing clinical trial
testing;
◆ Developing IVD kit;
◆ Conducting regulatory
clearance;
◆ Supporting patients and
physicians;
◆ Commercializing the test.
The standardized testing at a centralized
laboratory has proven to be a valuable
tool that enhances PML risk assessment.
The approach:
https://www.thejournalofprecisionmedicine.com/the-journal-of-precision-medicine/precision-medicine-dx-leads-to-rx/ 10/195/5/2021 Precision Medicine: Dx leads to Rx
◆ eliminates inter-lab
variability for patients;
◆ simplifies test ordering for
physicians;
◆ provides medical
informatics that improve
utilization of the test to
identify the right patients.
This approach marks a significant step
forward in the personalization of clinical
management of MS patients who may
benefit from natalizumab, and Quest
Diagnostics has successfully scaled up the
testing capability to meet the demand.
The STRATIFY JCV program demonstrates
the benefits of collaboration between
pharmaceutical and diagnostic companies
to bring important medical innovations to
market in an e icient way.
https://www.thejournalofprecisionmedicine.com/the-journal-of-precision-medicine/precision-medicine-dx-leads-to-rx/ 11/195/5/2021 Precision Medicine: Dx leads to Rx
Case study #2: Rare disease – HDV
program for Eiger Pharmaceuticals for
Lonofarnib
Overall process followed for this case:
Develop a new test → dentify patients
utilizing the data → support clinical
recruitment → go to commercialization
Quest Diagnostics worked with Eiger
Biopharmaceuticals on a complex phase 3
Hepatitis Delta Virus (HDV) trial. Knowing
that patient identification and
pre‑screening is the most challenging (and
costly) step in clinical trials, Quest
developed a patient‑centric Quantitative D
Virus RNA6 to identify the right patients.
Since HDV is underdiagnosed with no
current treatments available, many
patients with HBV also have HDV but are
unaware/ untested. Bearing this in mind,
Quest took a multi‑pronged approach to
identifying HDV+ patients to enroll in the
trial:
1. Provided a national
mapping of HBV, HDV
patients and care teams
2. Identified >400 HDV+
patients for patient outreach
proximal to sites
3. Implemented a sponsored
testing program to known
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HBV+ patients for HDV
screening
Our tailored approach to patient
recruitment includes doing more upfront
work to preprofile patients based on
relevant lab tests/ results and ICD‑10
codes, and then using the most
cost‑e ective methods to reach out to
highly motivated patients. This approach,
along with careful consideration of patient
convenience (e.g., through Patient Service
Centers and mobile healthcare options),
allows us to maximize trial enrollment, as
shown in Figure 2. Quest’s highly e ective,
tailored outreach to patients and
providers is committed to building clinical
trial awareness to address many of the
industry challenges with clinical trial
involvement.
Conclusion: Dx to Rx – the key to
advancing precision medicine
Early phase clinical development for
precision medicine starts by combining a
data‑driven stratification of patient
sub‑groups (by, e.g., well‑defined
exclusion/inclusion criteria) with the
ability to reach into a diverse community
to facilitate trial planning, recruitment,
and enrollment. As diagnostic companies
take on more challenging cases (as
https://www.thejournalofprecisionmedicine.com/the-journal-of-precision-medicine/precision-medicine-dx-leads-to-rx/ 13/195/5/2021 Precision Medicine: Dx leads to Rx
described in the cited Case Studies),
identification of these patient subgroups
has become increasingly complicated.
Furthermore, devising novel diagnostic
tests takes a new way of looking at
diagnostics and pharmaceutical
development. To get that new perspective,
Quest utilizes a team approach to
understand the medical ecosystem for the
successful, planning, reach, and
understanding of the information
provided in an increasingly crowded and
complicated landscape. Quest’s team
approach integrates perspectives from its
clinical partners; Ameripath pathology
luminaries; Information Ventures (data
analytics); regulatory groups; and disease
specific clinical franchises to customize a
plan created for clients. We at Quest have
learned to achieve the promise of
precision medicine by soliciting the input
of these groups to launch successful
diagnostics for precision medicine
applications. We point to our success in
the cited Case Studies as a model to
motivate others to realize the promise of
precision medicine for better patient
management.
Acknowledgements
The authors would like to acknowledge
the work and support by the Quest
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Diagnostics team. Special thanks to Dr Jay
Wohlgemuth, Senior Vice President, R&D,
Medical and Chief Medical O icer; Richard
Heichemer, Senior Director, Precision
Medicine; Dr Nicholas Conti, Executive
Director, Business Development; Pamela
Wong, Assistant General Counsel; Andrea
Luker, Director of Marketing; and the
Quest Diagnostics Healthcare Analytics
Solutions team.
Mridula Iyer, Ph.D.,
currently serves as the
General Manager,
Precision Medicine at
Quest Diagnostics leading
the Precision Medicine
business for all
therapeutic areas. Dr. Iyer’s professional
experience spans the academic Pharma
and biotechnology industry. At Quest
Diagnostics, she is responsible for leading
the Pharma Services business including
providing strategic direction to the
Precision Medicine/Companion Dx
business, working closely with other
teams to align with the market needs. Dr
Iyer leads Programs with Pharma
companies that include Custom Testing,
Commercialization of CDx tests, REMS and
End -End services including ssPMA
projects. Prior to joining Quest
Diagnostics, Dr Iyer was at AZ as Director,
https://www.thejournalofprecisionmedicine.com/the-journal-of-precision-medicine/precision-medicine-dx-leads-to-rx/ 15/195/5/2021 Precision Medicine: Dx leads to Rx
Commercial for Companion Diagnostics,
at Molecular Health as Director of Product
Marketing and with Qiagen Inc. leading
their North American Molecular
Diagnostics marketing and Global Product
Management teams.
Yuri Fesko, M.D., is
Medical Director of
Oncology at Quest
Diagnostics. As a leading
oncologist, Dr. Fesko
plays a key role in helping
Quest advance the fi eld
of precision medicine and give new hope
to people with cancer. Prior to joining
Quest in 2017, Dr. Fesko was Director of
Medical Oncology at the Duke Cancer
Institute in Raleigh, North Carolina, where
he was responsible for the oncology
service line and development of inpatient
oncology, multiple network sites and
infusion centers. He also was responsible
for strategies including the determination
of appropriate clinical trials for population
and resource utilization. Dr. Fesko received
his bachelor’s degree and medical degree
from Case Western Reserve University
School of Medicine. He is certified by the
American Board of Internal Medicine in
hematology and medical oncology.
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precisionmedicine-readiness-report-2019-
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25/whats-all-the-fuss-about-precision-
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detail/37889/hepatitis-d-virus-rna-
quantitative-real-timepcr?
p=r&q=HepatitisDVirus(HDV)Antibody,Total&cc=MASTER
* TYSABRI is a trademark of Biogen Idec
Inc. and Elan Corporation, plc. STRATIFY
JCV is a trademark of Biogen Idec.
NEXT
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