Download SureGene-January

Your patients are unique
They deserve personalized treatment
STA2R provides answers to important treatment defining questions!
Is olanzapine likely to have enhanced efficacy?
Do consensus data recommend avoiding risperidone due to altered
metabolism?
Are SSRIs likely to have decreased efficacy and increased risk
of side effects?
WHAT IS SULT4A1?
Sulfotransferase family 4A, member 1 is a brain sulfotransferase with many
interesting properties.
However, its exact activities and mechanisms remain
unknown.
• Highly expressed in areas thought to be involved in etiology of psychosis
• Highly conserve through-out evolution
– Minimal difference between mouse and man
– No coding variants in man, just regulatory variation
• Binds numerous classes of molecules that might impact psychosis
– Catecholamines – norepinephrine, epinephrine, isoprenoline (but not dopamine)
– Neurosteroids
– Thyroid hormones
SULT4A1-1 status impacted response to olanzapine in
the multiple studies, including CATIE
Percentage of SUL4A1-1 positive and negative Caucasian patients that achieved
clinically significant response in Phase I of the CATIE Study
1 in 5 schizophrenia patients
will be hospitalized in a given year.
1 in 2
hospitalized
patients will
return to
the hospital
within a year.
Treating SULT4A1-1 positive Caucasian patients with
olanzapine or quetiapine reduced the risk of hospitalization
by over 80% in the CATIE Study
Percentage of SUL4A1-1 positive and negative Caucasian patients who returned to the
hospital within one year after starting a new antipsychotic therapy in the CATIE Study
Based on the answer to the first two questions STA2R
identifies three broad classes of patients based on
likely response to antipsychotics
Is olanzapine likely to have enhanced efficacy?
YES
Olanzapine treated patients are more likely to achieve
clinically significant response and less likely to be
hospitalized than patients treated with other drugs
Olanzapine first line
Olanzapine unlikely to offer efficacy advantage over other drugs delivering less benefit
Do consensus data recommend avoiding risperidone due to
altered metabolism?
No
Risperidone is likely to be metabolized normally and should
be used as directed
Risperidone should be avoided if possible or extreme care should be taken to
manage the dose
Risperidone first line
First line????
Serotonin Transporter
The STA2R panel tests for genetic variation in the serotonin transporter gene (SLC6A4) that
impacts response to SSRIs.
Promoter variants lead
to altered transporter
production
Response to SSRIs is
influenced by number
of LA versions of
SLC6A4
Promoter
SLC6A4 gene
SS version
LG version
LA version
Lower expression
Lower expression
Higher expression
2 copies of LA version – Normal responders
Expected response to SSRIs
1 copy of LA version – Intermediate responder
Possible increased risk of poor response and adverse events
0 copies of LA version – Poor responder
Increased risk of poor response and adverse events
What is the appropriate time to use STA2R?
Initial medication selection: For patients currently not on medication
Treatment switch: Poor efficacy, tolerability, or satisfaction
Severe treatment failure: Exacerbations of psychosis
SUREGENE DOES NOT RECOMMEND STA2R FOR PATIENTS EXHIBITING AN ACCEPTABLE
CLINICAL RESPONSE TO CURRENT THERAPY
Is STA2R reimbursed? What is the clients responsibility?
Plan
Coverage
Client responsibility
Medicaid
Covered
No co-pay
Medicare
Covered
No co-pay
Private insurance
Coverage levels vary
In-network for many
national carriers
Plan rules dictate co-pay
Patient assistance program
No collections
Self-pay
NA
Patient assistance program
Sample Test report
Key treatment impacting questions
Is Olanzapine likely to have enhanced efficacy? (YES)
Client should be prescribed olanzapine (quetiapine if AEs unmanageable)
Do consensus data recommend avoiding risperidone? (YES)
Risperidone should be avoided
Are SSRI’s likely to have decreased efficacy? (YES)
Use non-SSRI antidepressants to manage co-morbid depression
Do the detailed results below provide dosing recommendations? (YES)
Check detailed results for dosing guidance
SULT4A1-1
Phenotype
THERAPEUTIC IMPLICATIONS (adapted from published resources)
POSITIVE
Consider olanzapine. SULT4A1-1 positive patients have been shown to
demonstrate enhanced treatment efficacy and reduced hospitalization risk when
treated with olanzapine compared to both SULT4A1-1 negative patients treated
with olanzapine and SULT4A1-1 positive patients treated with risperidone.
CYP2D6
Phenotype
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Avoid
Alternative Consideration Adjust Dosage Adjustment
Poor Metabolizer Risperidone† Quetiapine, olanzapine,
clozapine
Venlafaxine†
Citalopram, sertraline
Amitriptyline†
Citalopram, sertraline
Aripiprazole†
10 mg/day maximum
Clomipramine†
Decrease 50%
Doxepin†
Decrease 60%
Haloperidol†
Decrease 50%
Imipramine†
Decrease 70%
Nortriptyline†
Decrease 60%
Zuclopenthixol†
Decrease 50%, or
flupenthixol, quetiapine,
olanzapine, clozapine
SLC6A4
Phenotype
Poor
Responder
THERAPEUTIC IMPLICATIONS (adapted from published resources)
Decreased serotonin transporter expression expected. Risk of
decreased response to SSRI-based therapies and increased risk of
adverse events. Consider non-SSRI antidepressant therapies, such as
SNRIs or tricyclic antidepressant alternatives.
CYP2C19
Phenotype
THERAPEUTIC IMPLICATIONS (adapted from published
resources)
Poor
Metabolizer
Decreased metabolic clearance
expected.
Adjust
Dosage
Imipramine†
Sertraline†
CYP1A2
Phenotype
HYPERINDUCER
Adjustment
Decrease 30%
Decrease 50%
THERAPEUTIC IMPLICATIONS (adapted from published
resources)
Rapid metabolism expected, especially in smokers. Consider dose
increases for medications inactivated by CYP1A2 particularly in
smokers, or alternative medications. Common CYP1A2 medications
next page.
Competitive positioning
Only reference competition when specifically asked!
Key points of differentiation
STA2R is the only test to offer:
1. Clinical efficacy data, including reduction in hospitalization rates
2. Inclusion criteria, e.g. recommending olanzapine
3. Dosing recommendations
4. Both Medicare and Medicaid billing
5. Proprietary markers
6. Research oriented company