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Precision Medicine
From Promise to Practice
PRECISION ONCOLOGY IS THE FUTURE OF CANCER CARE.
Most cancers harbor mutations
leading to disrupted biological
pathways and tumor initiation.
Tumor genome data informs cancer
treatment and clinical pathways,
resulting in better health outcomes.
New cancer therapies target the
molecular pathways that lead to
tumor genesis and progression.
New Approaches: Precision Medicine and Immunotherapy
Recent investments in biomedical research have led to major advances
in precision medicine and immunotherapy. In 2016, the Food and Drug
Administration approved:
•
•
•
16 new and expanded use cancer therapies1
First liquid biopsy diagnostic test for lung cancer mutations 2
First next-generation sequencing diagnostic test to identify patients with advanced ovarian cancer
eligible for a particular cancer treatment3
1 US Food and Drug Administration: Hematology/oncology (cancer) approvals & safety notifications. ww.fda.gov/drugs/informationondrugs/approveddrugs/ucm279174.htm
2 US Food and Drug Administration: cobas EGFR Mutation Test v2. www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm504540.htm
3 US Food and Drug Administration: Rucaparib. www.fda.gov/Drugs/ InformationOnDrugs/ApprovedDrugs/ucm533891.htm
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Precision Cancer Treatment – a new Paradigm
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A Three Year Trend
In 2016, for the third year in a row, personalized medicines accounted for
more than 20 percent of all new molecular entities (NMEs) approved by the
Us Food and Drug Administration (FDA).
A New Molecular Entity
(NME) or New Chemical
Entity (NCE) is a drug or
chemical that is without
precedent among
regulated and approved
drug products. The NME
designation indicates
that a drug in
development is not a
version or derivative of
an existing and
previously investigated,
trialed and approved
substance. Being labeled
as entirely 'new' or firstin-class molecule
dictates that certain
types of clinical trials
must be run, and that
particular attention must
be paid to proving a
drugs safety.
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Newly Approved Medicines
The six personalized medicines approved in 2016 include:
1.
Rubraca (rucaparib) for the treatment of advanced ovarian cancer. The decision to use this
product is informed by the BRCA1/2 biomarker status in patients.
Personalized Medicine in Oncology
2.
3.
Exondys 51 (eteplirsen) for the treatment of Duchenne muscular dystrophy. The decision to
use this product is informed by the DMD mutation biomarker status in patients.
Nowhere is the transformation of healthcare toward
medicineformore
clear that
in oncology.
the The
Epclusa personalized
(sofosbuvir and velpatasvir)
the treatment
of chronic
hepatitis C Of
infection.
decision to use thissix
product
is informed by
the HCV
genotype status
of the viral infection in
personalized
NMEs
approved
in 2016,
patients.
three are oncology drugs.
4.
Tecentriq (atezolizumab) for the treatment of advanced or metastatic urothelial cancer and
metastatic non-small cell lung cancer. The decision to use this product is informed by PDL1 expression levels in the tumors of patients.
5.
Venclexta (venetoclax) for the treatment of chronic lymphocytic leukemia. The decision to
use this product is informed by the chromosome 17p deletion biomarker status in patients.
6.
Zepatier (elbasvir and grazoprevir) for the treatment of chronic hepatitis C infection. The
decision to use this product is informed by the HCV genotype 1 and 4 biomarker status of the
viral infection in patients.
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Newly Approved Indications
FDA also approved several significant new personalized medicine
indications for previously approved drugs in 2016. These approvals
redefine the drugs’ intended populations and provide patients with effective
personalized treatment options.
The list of new personalized medicines in 2016 should therefore be
complemented with reference to newly approved indications for:
• Imbruvica (ibrutinib),
• Opdivo (nivolumab),
• Keytruda (pembrolizumab) and
• Tecentriq (atezolizumab) for new molecularly defined subsets of patients.
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Pharmacogenomic Biomarkers in Drub Labeling
Total number of FDA - approved drugs with biomarker
information provided on their drug label*
Number of Therapies with Biomarker Info
on their Drug Label
180
165
160
140
132
120
106
100
81
80
60
40
36
20
0
2006
5
2008
2010
2012
2014
2016
2018
238 pharmacogenomics biomarkers
2017
165
61 / 165 classified
Oncology/Hematology
are included on FDA-approved drug label*
Source:https://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm Information last updated 03/14/2017
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The FDA has approved targeted therapies for the treatment of some patients
with the following types of cancer – “on label”:
Adenocarcinoma of the stomach or gastroesophageal junction: Trastuzumab (Herceptin®), ramucirumab (Cyramza®)
Bladder cancer: Atezolizumab (Tecentriq™), nivolumab (Opdivo®)
Brain cancer: Bevacizumab (Avastin®), everolimus (Afinitor®)
Breast cancer: Everolimus (Afinitor®), tamoxifen (Nolvadex), toremifene (Fareston®), Trastuzumab (Herceptin®), fulvestrant (Faslodex®), anastrozole
(Arimidex®), exemestane (Aromasin®), lapatinib (Tykerb®), letrozole (Femara®), pertuzumab (Perjeta®), ado-trastuzumab emtansine
(Kadcyla®), palbociclib (Ibrance®), ribociclib (Kisqali®)
Cervical cancer: Bevacizumab (Avastin®)
Colorectal cancer: Cetuximab (Erbitux®), panitumumab (Vectibix®), bevacizumab (Avastin®), ziv-aflibercept (Zaltrap®), regorafenib
(Stivarga®), ramucirumab (Cyramza®)
Dermatofibrosarcoma protuberans: Imatinib mesylate (Gleevec®)
Endocrine/neuroendocrine tumors: Lanreotide acetate (Somatuline® Depot), avelumab (Bavencio®)
Head and neck cancer: Cetuximab (Erbitux®), pembrolizumab (Keytruda®), nivolumab (Opdivo®)
Gastrointestinal stromal tumor: Imatinib mesylate (Gleevec®), sunitinib (Sutent®), regorafenib (Stivarga®)
Giant cell tumor of the bone: Denosumab (Xgeva®)
Kidney cancer: Bevacizumab (Avastin®), sorafenib (Nexavar®), sunitinib (Sutent®), pazopanib (Votrient®), temsirolimus (Torisel®), everolimus
(Afinitor®), axitinib (Inlyta®), nivolumab (Opdivo®), cabozantinib (Cabometyx™), lenvatinib mesylate (Lenvima®)
Leukemia: Tretinoin (Vesanoid®), imatinib mesylate (Gleevec®), dasatinib (Sprycel®), nilotinib (Tasigna®), bosutinib (Bosulif®), rituximab
(Rituxan®), alemtuzumab (Campath®), ofatumumab (Arzerra®), obinutuzumab (Gazyva®), ibrutinib (Imbruvica®), idelalisib (Zydelig®), blinatumomab
(Blincyto®), venetoclax (Venclexta™), ponatinib hydrochloride (Iclusig®)
Liver cancer: Sorafenib (Nexavar®)
Lung cancer: Bevacizumab (Avastin®), crizotinib (Xalkori®), erlotinib (Tarceva®), gefitinib (Iressa®), afatinib dimaleate (Gilotrif®), ceritinib
(LDK378/Zykadia™), ramucirumab (Cyramza®), nivolumab (Opdivo®), pembrolizumab (Keytruda®), osimertinib (Tagrisso™), necitumumab
(Portrazza™), alectinib (Alecensa®), atezolizumab (Tecentriq™)
Lymphoma: Ibritumomab tiuxetan (Zevalin®), denileukin diftitox (Ontak®), brentuximab vedotin (Adcetris®), rituximab (Rituxan®), vorinostat
(Zolinza®), romidepsin (Istodax®), bexarotene (Targretin®), bortezomib (Velcade®), pralatrexate (Folotyn®), ibrutinib (Imbruvica®), siltuximab
(Sylvant®), idelalisib (Zydelig®), belinostat (Beleodaq®), obinutuzumab (Gazyva®), nivolumab (Opdivo®), pembrolizumab (Keytruda®)
Multiple myeloma: Bortezomib (Velcade®), carfilzomib (Kyprolis®), panobinostat (Farydak®), daratumumab (Darzalex™), ixazomib citrate
(Ninlaro®), elotuzumab (Empliciti™)
Myelodysplastic/myeloproliferative disorders: Imatinib mesylate (Gleevec®), ruxolitinib phosphate (Jakafi®)
Neuroblastoma: Dinutuximab (Unituxin™)
Ovarian epithelial/fallopian tube/primary peritoneal cancers: Bevacizumab (Avastin®), olaparib (Lynparza™), rucaparib
camsylate (Rubraca™), niraparib tosylate monohydrate (Zejula™)
Pancreatic cancer: Erlotinib (Tarceva®), everolimus (Afinitor®), sunitinib (Sutent®)
Prostate cancer: Cabazitaxel (Jevtana®), enzalutamide (Xtandi®), abiraterone acetate (Zytiga®), radium 223 dichloride (Xofigo®)
Skin cancer: Vismodegib (Erivedge®), sonidegib (Odomzo®), ipilimumab (Yervoy®), vemurafenib (Zelboraf®), trametinib (Mekinist®), dabrafenib
(Tafinlar®), pembrolizumab (Keytruda®), nivolumab (Opdivo®), cobimetinib (Cotellic™), alitretinoin (Panretin®), avelumab (Bavencio®)
Soft tissue sarcoma: Pazopanib (Votrient®), olaratumab (Lartruvo™), alitretinoin (Panretin®)
Systemic mastocytosis: Imatinib mesylate (Gleevec®)
Thyroid cancer: Cabozantinib (Cometriq®), vandetanib (Caprelsa®), sorafenib (Nexavar®), lenvatinib mesylate (Lenvima®)
Source: https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet
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Drug Development – Biopharmaceutical Companies ARE committed
Personalized medicine is rapidly coming of age. Drug development
pipelines are full of new targeted therapies that offer the hope of
effective new treatment options for patients.
Biopharmaceutical companies nearly doubled their R&D investment
in personalized medicines over the past five years and expect to
increase their investment by an additional 1/3 in the next five years.
Biopharmaceutical researchers also predict a 69% increase in the
number of personalized medicines in development over the next five
years.
Source: Tufts Center for the Study of Drug Development, “Personalized Medicine Gains Traction but Still Faces Multiple Challenges,” Impact Report, May/June
2015, Volume 17, Number 3
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Genetic/Genomic Diagnostics
More than 5,500 new Genetic/Genomic Testing products came to
market between April 2015 and September 2016.*
Source: Concert Genetics – formerly NextGxDx – The current landscape of genetic testing - 2016
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Coverage and Payment Policy
Coverage and Payment policies in both the public and private sectors
play a critically important role in ensuring patient access and encouraging
continued innovation.
Healthcare policy leaders have contended that in order “to stimulate the
development of a more robust diagnostics pipeline and to harness the
benefits of personalized medicine in patient-centered care delivery,
policymakers must create an environment that encourages increased
investment in diagnostics, enables new advances in patient care that are
safe, accurate and reliable, and establishes a viable pathway toward
patient access.”*
Source: Abernethy, A, Abrahams, E, Barker, A, et al. Turning the tide against cancer through sustained medical innovation: The pathway to progress. Clinical Cancer
Research. 2014;20(5): 1081-1086.
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Coverage and Payment Policy
• Evidence Requirements
• Widespread insurance coverage of diagnostic tests, for example,
will likely require practice-based evidence demonstrating value.
• Obtaining the real-world data necessary for generating this
evidence is difficult unless the products and services are covered
by payers.
• Value Assessment Frameworks
• Tools for supporting health care decision-making by quantifying the
value of treatments
• Many of the frameworks, however, have been criticized for failing
to account for the heterogeneity of treatment effects
• Value-Based Payment Models
• CMS and private payers are also proposing new, “value-based”
payment models, also known as “alternative payment models”
(APMs), that seek to drive improvements in care quality and
efficiency.
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Clinical Integration – Operationalizing Precision Medicine
Integrating personalized medicine into health care requires:
• increasing awareness and understanding of personalized medicine
concepts amongst the public and health care workforce;
• placing a greater emphasis on patient perspectives;
• recognizing the value of molecular pathways in guiding care;
• building new infrastructure and information management processes;
• and reshaping health care delivery to ensure access to personalized
medicine technologies and services.
To successfully integrate personalized medicine into health care,
providers will need to implement a range of programs and processes in
each of these areas.
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2016 – meaningful progress
Despite ongoing challenges in the areas of
scientific discovery, diagnostic regulatory policy,
reimbursement and integration of new
technologies into clinical practice, the
commitment witnessed in 2016 anticipates a shift
away from one-size-fits-all, trial-and-error
medicine and toward a health care system that
utilizes molecular information to improve
outcomes and make the health care system more
efficient.
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Demonstrated Real-World Success
Better outcomes
Lower costs
Change in Physician
Decision-making
More drug reimbursed
Workflow efficiencies
23 PFS weeks on precision medicine vs 12 PFS
weeks on standard of care1
$4,665 per PFS-week per patient on precision
oncology vs. $5,000 on standard of care1
64% of patients had their care management changed1
82% of targeted therapy orders successfully obtained
through insurance approval or clinical trials2
4-fold increase in molecular tumor board throughput
1. Haslem, Derrick S., et al. "A Retrospective Analysis of Precision Medicine Outcomes in Patients With Advanced Cancer Reveals Improved Progression-Free Survival Without Increased Health Care Costs." Journal of Oncology Practice (2016):
JOPR011486.
2. Nadauld, Lincoln, et al. "Implementation of a precision cancer program in an integrated health care system." ASCO Annual Meeting Proceedings. Vol. 33. No. 15_suppl. 2015.
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