Drug Class
Insight
HEMOPHILIA
Background, new developments, key strategies
INTRODUCTION
Hemophilia is a rare, inherited bleeding disorder in which
the blood does not clot properly.
• 20,000 patients in the US1
• Occurs in 1
of 5,000 male births
• Affects MALES almost exclusively
• Extremely rare, but extremely expensive:
Ranks 8th most costly for employers for
1
1
all specialty diseases2
Hemophilia is caused by a mutation that disrupts the body’s
ability to produce clotting factor proteins. There are two main
forms of the disease, labeled A and B.1
Low levels of clotting factor can lead to spontaneous bleeding
in the joints or internal organs, or even inside the skull.
Uncontrolled bleeding can cause joint disease, seizures and
paralysis or death.1
Hemophilia can be mild, moderate, or severe. The lower the amount
of the factor, the more likely it is that bleeding will occur.1
MISSING LINK
Lack of clotting factor reduces the body’s ability to control bleeding.
Injury Occurs
Injury to blood vessel results in bleeding.
Damaged area
Natural clotting factor
Vessel constricts and clotting factors are activated.
Normal
atural clotting factor helps
N
form a strong platelet plug.
A stable fibrin mesh forms a
sealed clot over the platelet
plug to stop the bleeding.
Hemophilia
Less clotting factor
Lack of natural clotting
factor means only a weak
platelet plug can form.
Incomplete fibrin mesh
allows bleeding to continue.
Adapted from: Human Disease: Blood Clot Disease (Hemophilia). Jan 26, 2015. Accessed at: http://humansanatomy.org/2015/01/26/bloodclot-disease-hemophilia/ on 02.26.2015.
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Hemophilia Insight Report
All but the mildest forms of hemophilia are extremely expensive to treat. Unfortunately,
the majority of people with hemophilia have the most severe form.
Of all people with hemophilia…
60%
Severe: less than 1% of
normal level of clotting
factor; constant danger
of bleeding episodes
25%
Mild: 6-30% of normal clotting factor; may
not be diagnosed until after serious injury
15%
Moderate: 1-5% of normal clotting factor;
some possible spontaneous bleeding, or
after injury
Nature Outlook: Haemophilia. A Primer on Haemophilia. Dec 16, 2014
Critical Breakthrough:
Replacement Clotting Factor
Compact, effective forms of replacement clotting
factor helps many hemophilia patients live
near-normal lives.3
500
500
Factor VIII
Concentrate
Factor IX
Concentrate
Hemophilia therapy consists of replacement therapy — artificially raising
a patient’s level of clotting factor via infusion.3
Fresh plasma contains only trace amounts of clotting protein and huge amounts were needed to control
bleeding. Researchers learned to make concentrated forms of factor, but these still required thousands of units
of donated plasma to prepare just one unit of concentrate.3
Modern factor concentrates are made either with donated human blood plasma, or, beginning in the 1990’s, patients
began using genetically engineered clotting factor.3
Both forms of clotting factor are easy to store, mix, and use at home, so many patients self-administer their factor. It only
takes about 15 minutes to receive the factor.3
Immunity
Some patients develop immunity to their infusions
About 30% of type A and 5% of type B patients on preventive therapy develop
immunity to the clotting factors called inhibitors.4 Inhibitors make treatment
of bleeding episodes much more complicated, which drives up factor costs –
up to or over $1 million per year is not uncommon.4
≥$1 million
Total annual cost
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Hemophilia Insight Report
UNDERSTANDING TREATMENT COSTS
Hemophilia treatment costs can be extremely variable at the individual patient level. At the aggregate level, we can expect
overall treatment spending to rise over time as hemophilia patients live longer and as new treatments come into play.
Clotting factor costs
One key cost variable is how much replacement clotting factor a patient needs. Mild and moderate cases require
relatively little replacement factor, while severe cases need much more. Patients on preventive therapy use the most
replacement factor but also show fewer bleeding episodes and ER visits.
Total medical and indirect costs per year
$350k
94%
Nearly all spending (94%)
for severe cases is due to
factor costs. Compare to
just over half (54%) for
mild cases.
$300k
$250k
$301,392
$201,471
$200k
$150k
54%
$59,101
$84,363
Mild
Moderate
$50k
$0k
Severe
(On-demand treatment)
Severe
(Preventive treatment)
Journal of Medical Economics. Burden of illness: direct and indirect costs among persons with hemophilia A in the United States.
Mar 9, 2015. [Epub ahead of print.] Accesses at: http://www.ncbi.nlm.nih.gov/pubmed/25660324 on 04.20.2015.
Immunity (inhibitors) to factor infusions
The chart below illustrates the explosive effect inhibitors have on costs when inhibitors and comorbidities are added.
Health Care Costs for Hemophilia in Commercially Insured Populations
$9.0k
Without
inhibitors 
Including
inhibitors 
$8.0k
$7.0k
$6.0k
$5.0k
$4.0k
$3.0k
Total Annual
Medical Cost
$696,279
$831,866
$577,640
$2.0k
$1.0k
$0k
$144,306
$142,057
All males with Type A
Children with Type A
Total Annual Medical Cost
Haemophilia (2012), 18, 268–275 DOI: 10.111 1/j.1365-2516.201 1 .02692.x
$188,056
Adults with Type A
plus HIV/HCV
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Hemophilia Insight Report
PREDICTING FUTURE TREATMENT SPENDING
While factor concentrate is expensive, purchase prices have remained fairly flat and are expected to remain so in the short term.5
Therefore, predicting costs over the short term means understanding the age profile of each patient. Over the longer term, overall
treatment costs will go up due to demographic pressures.
Long Term
Costs will rise as growing numbers of patients live longer and develop additional complications (e.g., obesity, low bone density).
Average life expectancy for hemophiliacs.
Better treatments have increased Hemophiliac life expectancy
76
66
~10 years
less than
average
20
Normal U.S.
male lifespan
13
1900
1960
1990s /
Hemophiliacs who
have consistently
received proper
treatment
Today /
Newborn with
hemophilia living
in a developed
nation
National Hemophilia Foundation. History of Bleeding Disorders. Accessed at: https://www.hemophilia.org/Bleeding-Disorders/History-of-Bleeding-Disorders on 01.13.2015.
National Haemophilia Council. What is the life expectancy of someone with haemophilia? Accessed at: http://www.nationalhaemophiliacouncil.
ie/home/faqs/what_is_the_life_expectancy_of_someone_with_haemophilia/ on 01.13.2015.
Short Term
Hemophilia patients experience radical changes in the cost of their disease as they age.
Annual Health Insurance Expenditure Per Patient, $USD
Payer costs change significantly by patient age
$600,000
Hemophilia A
$500,000
Hemophilia B
Type B peak
$400,000
Type A change
$300,000
$200,000
$100,000
$0
0 5 10 15 2025 30 35 4045 5055 60 65
Age Years
American Society of Hematology: 56th Annual ASH Meeting & Exposition. The Changing Costs of Caring for Hemophilia Patients in
the U.S.: Insurers’ and Patients’ Perspectives. Dec. 9, 2014. Paper 199.
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Hemophilia Insight Report
PROMISING TECHNOLOGY
Some of the highest costs for hemophilia are due to patients who develop inhibitors (resistance) to the factor itself.6 Unfortunately,
treatments to overcome resistance are expensive (~$1 million) and not always effective.6 This promising research aims to prevent
the immune system from producing inhibitors.
Preventing Inhibitor resistance
Genetically engineered plant cells can be coaxed to produce type A and B factor proteins as part
of their normal cell machinery. While plant proteins cannot be used to directly promote clotting,
they can help “desensitize” the body’s immune system and prevent rejection.7 Note: Although
human figures are used below, these studies are still in the animal phase. Human trials
are expected to begin sometime in 2015.7
1
3
Lettuce leaf chloroplasts are genetically
engineered to produce human clotting
factor protein.
About 10,000 chloroplasts are
in each cell.
chloroplasts
Engineered clotting protein
cell wall
The leaf cells protect clotting
proteins from stomach acids.
Instead, the engineered lettuce and
clotting protein is freeze dried, powdered
and administered by adding to food.
T he plant-based clotting protein
“defuses” the immune system.
Cells release proteins once inside
the intestinal tract.
Real clotting factor infusion can
proceed with no
allergic reaction.
Another protein is
added to help clotting
factor bind to the
intestinal wall.
Clotting proteins
are then processed
by the immune system
to produce tolerance.
2
4
The resulting plant-based factor cannot
be used directly to control bleeding.
Any existing
inhibitors are
reversed.
stomach
large
intestine
Leaf cell diagram adapted from: University of Cincinnati – Clermont. College Biology Home page: Cells & Organelles. Sept 5, 2011. Process
based on: Nature Outlook: Haemophilia. Lettuce Pills May Help Treat Haemophilia. Dec 16, 2014.
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Hemophilia Insight Report
OVERVIEW OF HEMOPHILIA MANAGEMENT PROGRAM
Integrated management allows for consistent management and holistic care coordination.
OptumRx Program Goals
Benefits
 Clinical Management
Provides individualized educational and clinical support for patients
to help improve adherence to achieve optimal outcomes.
 Utilization Management
 Aggressive contracting
 Available Networks
Ensure clinically appropriate and cost-effective utilization by using
the management strategies available to each client.
Leading to better drug pricing.
Access to efficient, quality care and deep discounts for many
specialty drugs.
 Assay Management
MEMBERS
Better health and support
and guidance
CLIENTS
Total cost control and program
management: clients can
achieve up to $0.66 PMPM
savings by exclusively using
participating providers*
PROVIDERS
We tightly manage how much factor medication is dispensed reduces
waste and can save thousands of dollars per patient per year.
Better health support
and guidance
DEDICATED CALL CENTER
We have a dedicated call center for hemophilia. The same specialty pharmacist within OptumRx Specialty Pharmacy will regularly
assess each patient’s needs.
• Ongoing support to recognize and prevent bleeds
• Comprehensive assessments 2-4X per year
• Teach patients and caregivers how to “self-infuse” at home
• Ensure ready access to clotting factor
• Conduct routine compliance and adherence calls
• Supplies needed such as needles, tubing, syringes, etc.
*Oxford Hemophilia Initiative covering FI clients during calendar 2014.
SPECIALTY PHARMACY
HEMOPHILIA PROGRAM
HTCS ARE LOCATED ACROSS
THE COUNTRY
The OptumRx Specialty Pharmacy hemophilia program is
designed to make patients as self-sufficient as possible.
We also work closely with regional Hemophilia Treatment
Centers (HTCs), that bring together specialty teams of
doctors, nurses, & health professionals.
The OptumRx Specialty Pharmacy Program connects
patients with the nearest local HTC which monitors
each patient’s treatment.
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Hemophilia Insight Report
MEET JOHN
What does it mean to
manage the total cost
of John's condition?
John was diagnosed with severe
hemophilia when he was an infant.
Without effective preventive therapy
he would risk spontaneous bleeding,
disability or death. John was transitioned
into our Hemophilia Specialty Pharmacy
Program shortly after his employer
switched to OptumRx.
Synchronize member touch
points and data into ONE system.
Opportunities
Traditional
PBM
1
2
3
Prior Authorization
YES
Assay Management
NOT OPTIMIZED
Adherence Programs
NOT OPTIMIZED
4
Clinical Management
Program
NOT OPTIMIZED
5
Connect members
with quality physicians
and Hemophilia
Treatment Centers
MISSED
6
Manage co-morbid
depression with
synchronized
behavioral referrals
MISSED

7
Weight monitoring
and healthy lifestyle
programs to encourage
condition-appropriate
exercises and diet
MISSED

OPTIMIZED*




OptumRx Connected Care
A traditional PBM looking only at pharmacy
claims or pharmacy solutions can miss
opportunities. Our ONE team approach
manages multiple consumer touch points
to promote real behavior change, like lower cost
alternatives, medication adherence or
engagement in clinical management programs.

Our Connected Care model leverages all member
touch points to capitalize on every opportunity to
guide each member to their best next health action.
* T he synchronized care management model described here depends on a minimum specific set of OptumHealth care
management services, plus OptumRx pharmacy services. Please speak to your OptumRx or UnitedHealthcare representative
for more information about how synchronization can work for you.
Connected Engagement:
Every interaction is
Online
an opportunity to
reduce health risk
and lower costs
Pharmacy
Health Care
Advisor
Mobile
Nurse
Advisor
Customer
Service
Synchronized Touch Points
Self Service
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+
Outreach
+
Inbound
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Hemophilia Insight Report
THE OPTUMRx DIFFERENCE: HEALTH CARE CONNECTED
Even ordinary PBMs can do an adequate job at the ordinary things PBMs do – negotiate discounts, pay claims, manage formularies
and so on. But OptumRx is more than an ordinary PBM: We are a complete pharmacy care services company.
We focus on managing total condition spending by connecting pharmacy’s impact across all benefits.
Connected Data
and Expertise
Incremental
3-6% savings*
compared to total
pharmacy spend
Connected Value
• Care Management,
Wellness, Behavioral
Program Connections
• Advanced Nurse Advisor
• Pharmacist Consults
• 360˚ Alert System
• Connected Medical,
Pharmacy, Specialty
Connected
Engagement
Core PBM Value
Like other PBMs, OptumRx
delivers savings through core
PBM programs
• PDL Management
Connected
Care
• Clinical Programs
• Utilization Management
• Exclusions
• Specialty Pharmacy
• Home Delivery
• Adherence programs
• Drug cost management
• Claims processing
• Network
*Estimated additional savings over traditional core PBM services based on
total pharmacy spend. Illustrative only; results may vary.
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Hemophilia Insight Report
References
1. C
enters for Disease Control and Prevention. Hemophilia
Facts. Aug 26, 2014. Accessed at: http://www.cdc.gov/
ncbddd/hemophilia/facts.html on 10.17.2014.
2. U
nitedHealth Center for Health Reform & Modernization,
Issue Brief. The Growth of Specialty Pharmacy. April, 2014.
Accessed at: http://www.unitedhealthgroup.com/~/media/
UHG/PDF/2014/UNH-The-Growth-Of-Specialty-Pharmacy.
ashx on 02.13.2015.
3. N
ational Hemophilia Foundation. History of Bleeding
Disorders. Accessed at: https://www.hemophilia.org/
Bleeding-Disorders/History-of-Bleeding-Disorders on
01.13.2015.
5. M
orningstar Healthcare Observer. The Hemophilia Market.
January 2013.
6. CDMI Report. Understanding Hemophilia: A Managed
Care Review. Fall 2013. Accessed at: http://www.cdmihealth.com/CDMI_Journal/Fall_2013/files/assets/FALL%20
2013_FINAL2.pdf on 01.30.2015.
7. N
ature Outlook: Haemophilia. Lettuce Pills May Help Treat
Haemophilia. Dec 16, 2014. Accessed at: http://www.
scientificamerican.com/article/lettuce-pills-you-heard-thatright-may-help-treat-haemophilia/ on 02.25.2015.
4. S pecialty Pharmacy Continuum. Hemophilia: Overview
and New and Emerging Treatments. May, 2014. Volume
3, Spring Issue. Accessed at: http://www.specialtypharmacycontinuum.com/ViewArticle.aspx?d=Clinical&d_
id=500&i=May+2014&i_id=1063&a_id=27523 on
01.28.2015.
For more information about how you can manage the cost of Hemophilia,
please contact your OptumRx representative.
www.optum.com
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