Transcript File - Life-Sci Diagnostics Group

Woman’s Health PGX Panel
for Drug Metabolism and
Health Risk
CF Testing
Are you slow or ultra rapid?
Pharmacogenomics Study
• Recent advances in the field of genomics have dramatically
accelerated the discovery of new genetic variations that
potentially underlie variability in drug response, making possible
the practice of personalized medicine through
pharmacogenomics.
CONFIDENTIAL
The GOAL of Pharmacogenetics:
The right drug for
the right patient at
the right dose.
CONFIDENTIAL
American Medical Association
“These advancements in personalized
medicine rely on knowledge of a
patient’s genotype and influences his or
her phenotype.
Using the principles of personalized
medicine, healthcare providers may be
better equipped to move beyond the
“one-size-fits-all” that defined much of
patient care in the past, to care that is
appropriate for unique patient
subgroups.”
http://www.ama-assn.org/ama/pub/physician-resources/medicalscience/genetics-molecular-medicine/news.page
CONFIDENTIAL
What does the FDA say about
personalized medicine?
“We’ve learned that this trial-and-error approach leads to
patient dissatisfaction, poor clinical outcomes, and greater
expense, especially for chronic diseases.
But in many situations this empirical approach is the best
approach we have. Personalized medicine aims to streamline
clinical decision making by using biological information available
through a genetic test or biomarker, and then saying, ‘based on
this profile, I think you're more likely to respond to Drug A or
Drug B, or less likely to have an adverse reaction with Drug C.’
The idea is to get patients on the right medication and to get
them on it sooner.”
Issam Zineh is Director, Office of Clinical Pharmacology (OCP), Center for Drug
Evaluation and Research/ FDA
CONFIDENTIAL
“One size does not fit all”
• Pharmacogenetic testing allows you to easily identify
•
•
•
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metabolizer status
There are 5 genes in the body that metabolize 75% of all
medication prescribed
There are 43 medications on the market with black box
label warnings due to genetic metabolizer status
(Codeine, Coumadin, Plavix, Coreg, Valium)
CYP2D6 metabolizes roughly 30% of all medications
prescribed
Pharmacogenetic testing is standard of care at Harvard,
Mayo Clinic, Vanderbilt, Scripps, Columbia
CONFIDENTIAL
Why perform Pharmacogenetic testing?
•
To identify the likelihood of an ADE
o An estimated 20-30% of pain patients have a genetic opioid (GOMD) metabolic defect.
• Tennant, Forest, MD, DPH
http://www.practicalpainmanagement.com/treatments/pharmacological/opioids/making-practical-sense-cytochromep450
o 2.2 billion ADE occur yearly with over 100,000 cases resulting in death.
• U.S. Food and Drug Administration Development Resources
http://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm110632.ht
m
•
To increase drug efficacy.
o Only 58% of patients who take prescription pain medication receive relief.
• Peter D. Hart Research Associates, Americans Talk About Pain: A Survey Among Adults Nationwide (August 2003):7
o Patients with reduced-function alleles have a 3.5-8 times greater risk of major adverse
cardiovascular events, with greatest risk in poor metabolizers of Plavix.
•
Tabassome Simon, M.D. et. al. Genetic Determinants of Response to Clopidogrel and Cardiovascular Events. N Engl J Med 2009;
360:363-375
o Drug treatment of psychiatric disorders is troubled by severe adverse effects, low
compliance and lack of efficacy in about 30 percent of patients.
•
Arranz, M.J. et al, Pharmacogenetics for the Individualization of Psychiatric Treatment, American Journal of Pharmacogenomics
2001;1(1):3-10
CONFIDENTIAL
Why perform Pharmacogenetic testing?
• To improve patient compliance
o Knowledge of their genetic test results has been proven to make
patients more likely to take medications as prescribed.
•
Charland, Scott L. Phar.D.. Medco Research Institute
• To reduce healthcare costs by preventing ADE.
o An estimated $136 billion is spent on treating ADE annually.
o Greater than total cost of cardiovascular or diabetic care
• U.S. Food and Drug Administration Development Resources
http://www.fda.gov/drugs/developmentapprovalprocess/developmentresources
/druginteractionslabeling/ucm110632.htm
o Prescription opioid analgesics are among the most common causes of
ADE.
•
The Joint Commission
http://www.jointcommission.org/assets/1/18/SEA_49_opioids_8_2_12_final.pdf
CONFIDENTIAL
Evidence PharmGKB
CONFIDENTIAL
Pharmacogenetic panels
•
Cardiac Panel
o Focus on cardiac drugs
•
Psychiatric Panel
o SSRIs, anti-depressants, others
•
Pain Management Panel
o Opiates, NSAIDs, etc.
•
Urology Panel
o Urology drugs
•
Personagene Panel
o Includes results from all panels
o Custom (select current medications)
• Woman’s Health PGX
CONFIDENTIAL
Pharmacogenetic panels
• Identifies Poor, Intermediate, Extensive and Ultrarapid
metabolizers for the following Cytochrome P450 (CYP) pathways:
CYP2C19, CYP2C9, CYP2D6 and CYP3A4/3A5
• Interprets data for cardiology, pain management, psychiatry and
urology. New Woman’s Health medications and risk for adverse
events during pregnancy .
• Validated for use on buccal swab (cheek), 50 ng DNA/reaction
• Turnaround time from receipt of buccal swabs is 3-5 business days
• CLIA compliant
CONFIDENTIAL
Metabolizer Category Definitions
• Ultra Rapid
Metabolizers (UM)
• Extensive
Metabolizers (EM)
• Intermediate
Metabolizers (IM)
• Poor Metabolizers
(PM)
CONFIDENTIAL
The PersonaGene™ Report
CONFIDENTIAL
How do you determine dosage?
CONFIDENTIAL
Woman’s Health PGX
• Includes drug specific for Woman’s health issues including
all prescription contraceptives, HRT medications, pain
medications, and psychiatric medications.
• Thrombosis panel includes MTHFR, Factor V Leiden,
Factor II as a measure for risk of Deep Vein Thrombosis
(DVT) and risk of complications during pregnancy.
CONFIDENTIAL
MTHFR
MTHFR mutation, A1298C
MTHFR mutation C677T
1
normal
No increased risk
no change needed
het
No increased risk
no change needed
Elevated homocysteine levels have been observed more frequently
among women with certain pregnancy complications, including
preeclampsia, placental abruption, recurrent pregnancy loss, and
giving birth to a small, low-birth-weight baby. MTHFR A1298C
mutations, when present with other genetic thrombophilic factors
(e.g., factor V Leiden or MTHFR C677T), dramatically increase risk for
venous thrombosis and/or hyperhomocysteinemia.
homo
Increased risk for hyperhomocysteinemia and
thromobophilia
normal
No increased risk
no change needed
het
No increased risk
no change needed
Thermolabile variant of the enzyme with
decreased activity. Increased risk for
hyperhomocysteinemia and thromobophilia
Closely monitor for hyperhomocysteinemia, DVT, and complications
during pregnancy. Elevated homocysteine levels have been observed
more frequently among women with certain pregnancy
complications, including preeclampsia, placental abruption, recurrent
pregnancy loss, and giving birth to a small, low-birth-weight baby.
homo
Knowing an individual’s MTHFR genotype can provide important clues in the treatment of patients presenting with hyperhomocysteinemia and other genetic factors that increase risks for deep vein thrombosis
(DVT). MTHFR status can help understand a patient response to medication dosages. Medications affecting folate metabolism, e.g. bile acid sequestrants, antacids, oral medications for diabetes, certain types of
chemotherapy and H2 blockers, may be more toxic in MTHFR mutation carriers than non-carriers.
CONFIDENTIAL
Factor V Leiden
Factor V
Leiden
Normal
No increase in risk
no change needed
het
No increase risk
no change needed
homo
Evaluate risk for use of estrogen-containing
contraceptives and HRT therapy. The presence of the
increased risk for thrombophilia and
factor V Leiden mutation increases the overall risk of
complications during pregnancy.
DVT by 17-fold when using estrogen containing drugs.
Closely monitor for DVT during pregnancy.
CONFIDENTIAL
Factor II
Factor II
(prothrombin)
normal
No increase risk
het
Possible increased risk for DVT
The relative risk for DVT in adults heterozygous for the
20210G>A allele is 2- to 5-fold increased
Increased risk for DVT
Using estrogen-containing oral contraceptives and hormones
increases the risk of blood clots. It has been shown that
women who have the prothrombin mutation increase the risk
of developing a DVT by about 16 times by using estrogencontaining oral contraceptives. Hormone replacement therapy
increases the risk of DVT by 2 to 4 times in those with the
prothrombin 20210 mutation. Therefore, women with the
prothrombin mutation should discuss the risks and benefits of
hormone use with their physician. Slight increase in risk for
DVT during pregnacy.
homo
CONFIDENTIAL
Cystic fibrosis (CF)
• Cystic fibrosis (CF), also known as mucoviscidosis, is a
genetic disorder that affects mostly the lungs but also the
pancreas, liver, kidneys and intestine. Long term issues
include difficulty breathing and coughing up sputum as a
resulting of frequent lung infections. Other symptoms
include sinus infections, poor growth, fatty stool, clubbing
of the finger and toes, and infertility in males among
others. Different people may have different degrees of
symptoms.
CONFIDENTIAL
CF Background
• CF is an autosomal recessive disorder. It is caused by the
presence of mutations in both copies of the gene for the
protein cystic fibrosis transmembrane conductance
regulator (CFTR).
• CFTR is involved in production of sweat, digestive fluids,
and mucus. When not functional usually thin secretions
become thick. The condition is diagnosed by a sweat test
and genetic testing.
CONFIDENTIAL
CF Testing
• CF is most common among people of Northern European
ancestry and affects about one out of every three thousand
newborns. About one in twenty five are carriers. It is least
common in Africans and Asians
• Couples who are pregnant or planning a pregnancy can have
themselves tested for the CFTR gene mutations to determine
the risk that their child will be born with cystic fibrosis. Testing
is typically performed first on one or both parents and, if the
risk of CF is high, testing on the fetus is performed. The
American College of Obstetricians and Gynecologists (ACOG)
recommends testing for couples who have a personal or close
family history of CF, and they recommend that carrier testing be
offered to all Caucasian couples and be made available to
couples of other ethnic backgrounds.
CONFIDENTIAL
CF
• Testing can be done from a buccal swab.
• In rare instances we can also do it from a vagina swab.
o Vaginal swabs are not ideal due to bacteria content.
CONFIDENTIAL