Market Access Overview in Hemophilia: Challenges and Opportunities

Market Access Overview in Hemophilia
Challenges and Opportunities
An overview of the disease, total patient populations in major hemophilia affected nations, treatments
(current and alternatives) and future outlook
©Niteo Partners Consulting
2015
www.niteo-partners.com 1

Contents
2015

Executive Summary
• Hemophilia is almost always inherited and caused due to mutations in the X chromosome and therefore
referred to as an X-linked disorder
• Patient population: More than 56% of the patient population remains unidentified
o Estimated worldwide : 400,000
o Identified patients : 176,730
o US, India, Brazil and China are the major markets of Hemophilia in terms of patient population
• Currently available treatment options: Replacement therapy, ITI therapy and Gene Therapy (advancements
have been made in this therapy area)
• The cost of Hemophilia varies significantly according to the age and life span of the patient
• Despite the extremely high costs, investments in gene therapy continue to grow and a genetic cure for
hemophilia no longer seems a distant possibility
• Long-acting recombinants, which have a considerably longer half-life period are about to enter markets
this year and could capture considerable market share
• The new treatments, especially gene therapy, look increasingly promising in trial phases and could
significantly change the treatment paradigm in years ahead. However, access to new and existing therapies
still remain highly restricted in most major markets
2015

INTRODUCTION: HEMOPHILIA
2015

Introduction: Hemophilia
• Hemophilia: A rare inherited bleeding disorder in which the ability of the body to form a clot during
haemorrhage is severely compromised
• This is attributed to a deficiency in clotting proteins (clotting factors) in the blood
• Hemophilia is genetically caused due to mutations in the X chromosome and is much more common in
males
• In acquired Hemophilia, the body produces antibodies (known as inhibitors) that attack clotting factors,
most often factorVIII. It is extremely rare and classified as type unknown
• Three main types of Hemophilia
2015
A
B
C

Diagnosis
• Hemophilia is diagnosed primarily by reviewing a patients family medical history as it is an inherited
condition
• Physical examinations and blood tests help determine the extent and severity of the condition
• People with known histories of the disease can have tests done during pregnancy to determine if the fetus
has inherited the condition. However, these may pose a threat to the fetus
• Hemophilia cases are generally diagnosed between 0-2 years after birth with the mean age for diagnosis
being 9 months[1]
• Blood clotting factor tests help to characterize the type and severity of the hemophilia condition
2015
Severity Levels of factor VIII or IX
No Hemophilia 50-100%
Mild Hemophilia Between 5% and 50%
Moderate Hemophilia Between 1% and 5%
Severe Hemophilia Less than 1%

Prenatal and Postnatal Diagnostics
2015

TOTAL PATIENT POPULATION –
HEMOPHILIA WORLDWIDE
Year 2013
2015

Facts and figures
• Estimated occurrence of the various types of Hemophilia in the United States (US)
2015
Estimated to
occur once in
5,000 live
male births in
US
One in 20,000
live male
births in US
Extremely
rare with an
estimated one
in 100,000
cases in the
US
A B C

Unidentified Patient Population
• Comparing this total with the estimated figure of 400,000 based on the probability of occurrence of the
disease, approximately 56% of the patient population remains unidentified
• The unidentified patient population can be better identified through early screening programs and disease
awareness campaigns
2015
2013: Total identified patients
Hemophilia type Number of patients
Hemophilia A 140,313
Hemophilia B 28,430
Hemophilia A (with inhibitors) 4,753
Hemophilia B (with inhibitors) 248
Hemophilia type unknown 2,986
Total identified patients 176,730

Choropleth: Global Registered Patients in 2013
2015
Source : World Federation of Hemophilia report on the annual global survey 2013

Total Patient Population in Different Countries in
2013
2015
(Patient Population > 5,000)

TREATMENT OPTIONS
2015

ReplacementTherapy
• The most widely used replacement therapy involves the intravenous injection of the missing clot factors
to help stop hemorrhaging
• Shortcomings of Replacement Therapy:
o Transmission of blood-borne disease through infected blood
o Development of antibody inhibitors
o Complications associated with delayed treatment
o Though there is still no permanent fix for hemophilia, most people through timely interventions, and with
milder forms of the disease can lead fairly normal lives
2015

Common Medications
2015
Product name
Source
Hemophilia A Helixate FS (CSL Behring LLC)
Kogenate FS (Bayer HealthCare)
Advate (Baxalta US Inc)
Recombinate (Baxter Healthcare Corporation, & Wyeth
BioPharma)
ReFacto (Pfizer)
Koate-DVI (Kedrion Biopharma)
Monoclate-P (CSL Behring LLC)
Hemofil M (Baxter)
Recombinant
Recombinant
Recombinant
Recombinant
Recombinant
Plasma
Plasma
Plasma
Hemophilia B Mononine (CSL Behring LLC)
AlphaNine SD (Grifols Biologicals Inc.)
BeneFIX (Wyeth Pharmaceuticals Inc.)
Profilnine SD (Grifols Biologicals Inc.)
Bebulin VH (Baxter)
Plasma
Plasma
Recombinant
Plasma
Plasma

AlternativeTreatments to ReplacementTherapy
2015

ITITherapy
• Treatment of patients who develop antibodies is challenging and done using a method called Immune
Tolerance Induction (ITI) therapy which is quite complex, expensive and lengthy
• A small percentage of Hemophilia patients develop antibodies as a part of the immune system response to
the factor concentrates rendering general treatments ineffective
• These antibody inhibitors affect 20-30%[8] of patients diagnosed with severe Hemophilia A and 2-5% of
patients with Hemophilia B
2015
Process flow of ITI Therapy

PAYERS IN MAJOR MARKETS
2015

Hemophilia Market in USA
• The payers in this market include both Federal Medicaid and Medicare programs as well as state
sponsored programs and employer sponsored private insurance
• The cost of Hemophilia varies significantly according to the age and life span of the patient
2015

Age and Cost Co-relation
2015
Source : American Society of Hematology

Cost ofTreatment
• Factor replacement concentrates, which are now the standard of treatment, account for 45% to 93% of
the total medical cost for Hemophilia
• Besides age and medication costs, variables in the cost of treatment can be disease severity, familial
clustering, phenotypic variability and morbidity influence costs
• The expenses of patients who develop inhibitor antibodies is significantly higher and is estimated at
USD 697,000annually per patient
• Indirect costs include individuals’ and caregivers’ lost productivity, caregivers’ unpaid costs, and
reductions in patients quality of life years (QALYs)
• Federal Hemophilia Treatment Centers (HTCs) treated 70% of all patients and achieved better
outcomes at lower costs as compared to other providers
2015

Average Inpatient Claims – US Market
2015
The cost of inpatient claims associated with Hemophilia is significantly greater than the
average claim
Source: Milliman actuarial study of Hemophilia 2013

Payer Coverage Criteria – US Market
• Being an inherited disorder, family history of the disease is a key criterion in insurance coverage
• New Affordable Care Act prohibits lifetime and annual limits on coverage and offers insurance to
uninsured people with pre-existing conditions is expected to positively impact Hemophilia patients
2015
Cost Saving Strategies adopted by Payers

Patient Population – Indian Market
• Only 16,456patients are registered as against a total estimated patient population of 54,454
• People suffering from hemophilia in India remain largely unidentified
• There is heavy under diagnosis with case detection rate of 0.9 per million as compared to 4.3 per million
in the US
2015

Burden of Hemophilia
• Annual costs incurred based on the severity of the condition and the frequency of occurrence:
• Hemophilia remains classified as a low-volume high-cost disease in India and most patients cannot afford
private health insurance
• The Insurance Act in India does not cover pre-existing hereditary disorders and advanced treatments like
factor concentrates remain costly
• The Indian market still heavily depends on relatively cheaper plasma derived concentrates which may turn
out to be a risky proposition given the spread of blood-borne disease such as HIV, HCV
2015
Category Annual frequency of bleeding episodes Annual Cost (USD)*
Severe 12-15 3,000 – 3,800
Moderate 6-8 1,500 – 1,900
Mild 3-4 750 – 1,000
*Conversion Rate: 1 USD = INR 66

LATEST ADVANCEMENTS
INTREATMENTS
2015

GeneTherapy
• Since Hemophilia is an inherited disorder attributed to Gene mutations, most research for a cure revolves
around gene therapy
• No gene therapy has been approved, though some successful clinical trials have been carried out in
animals as well as humans
• Recent studies published advocate the long term safety of such treatments
• With research in gene therapy gaining momentum a permanent cure for the condition seems on the
horizon
• Following are the list of companies or organisations that are advancing gene therapy based assets in the
pipeline:
2015
Gene Therapy Process

Recent Developments in GeneTherapy
2015
Company Disease Area Name Status
Baxter
International
Hemophilia B BAX-335 Initial data from Phase I/II clinical trial of
Hemophilia B reported in February 2015
Hemophilia A Undisclosed
UniQure Hemophilia B AMT-606 Phase I/II trial for Hemophilia B started in
2015
Dimension
Therapeutics
Hemophilia A/B Undisclosed Expects to start clinical testing in 2015
Spark
Therapeutics
Hemophilia B SPK-FIX Phase I/II trials in Hemophilia B in 2015
Biomarin
Pharmaceutical
Hemophilia A BMRN-270 Clinical testing in 2015
Sangamo
Biosciences
Hemophilia A/B Undisclosed Plans to submit Investigational New Drug
(IND) application in 2015
Biogen IDEC Hemophilia A/B Undisclosed Potential first trial in 2016

MARKET LANDSCAPE
2015

Market updates
•Despite the extremely high costs, investments in gene therapy continue to grow and a genetic cure for
hemophilia is no longer a distant possibility
•The global market for Hemophilia treatment is poised at USD 5 billion for Hemophilia A and USD 1 billion
for Hemophilia B
•Hemophilia patients tend to detest frequent short term interventions and new drugs are set to address this
need
•Long-acting recombinants, which have a considerably longer half life period are about to enter markets this
year and could capture considerable market share
•The new treatments look increasingly promising in trial phases from the view point of restricting inhibitor
development in patients who develop antibodies
2015

Innovative Drugs Pipeline – Hemophilia A
2015
Company Name Status Description
Biogen Idec / SOBI rFVIIIFc (BIIB031 or
Eloctate)
FDA and Health Canada approved in
summer 2014
Long-acting recombinant with extended half
life
Bayer BAY81 8973‐
(Kovaltry in the
U.S.)
FDA accepted Bayer’s license application
in the March 2015
Normal half life recombinant : full length‐
rFVIII manufactured without exposure to
human and animal proteins
Novo Nordisk Zonovate in Canada
and NovoEight in
the rest of the world
(Turoctocog alfa)
Approved by Health Canada in January
2015. NovoEight is approved by the FDA,
EMA, and regulatory authorities in Japan
and Australia
Normal half life recombinant : rFVIII
manufactured without exposure to human
and animal proteins
Octapharma Human cl rhFVIII‐
(simoctocog alfa)
Nuwiq
Marketing authorization granted in
Europe in August 2014 and Canada in
November 2014
First rFVIII with human like post‐
translational modifications, which it is hoped
will result in a lower rate of inhibitors
Novo Nordisk N8 GP (turoctocog‐
alfa pegol)
Phase III trial completed in March 2014 Recombinant with half life of 18.4 hours
Bayer BAY94 9027‐ Phase III trial completed in Feb 2014 Long acting plasma/albumin free, full length‐
rFVIII
Baxter Bax 855 Submitted application to the U.S. FDA in
Dec 2014
Pegylated, long acting, plasma/albumin free,‐
full length rFVIII‐
CSL Behring rVIII SingleChain‐ Results of Affinity Phase I/III study
released in June 2015
Novel recombinant single chain‐
factor VIII designed to overcome inhibitors
Chugai
Pharmaceutical
Co & Roche
Anti factor IXa/X‐
bispecific antibody
ACE910
Phase III trial by the end of 2015 Mimics coagulation factor VIII with a half life‐
of three weeks

Innovative Drugs Pipeline – Hemophilia B
2015
Company Name Status Description
Biogen Idec/ SOBI rFIXFc (BIIB029 or
Alprolix™)
Approved in US and Canada in 2015 Fc fusion technology to extend half-life by 2.5
times that of existing therapies
Emergent
Biosolutions
Ixinity in the U.S.
(previously IB1001)
FDA approved in May 2015 Normal half-life , 3rd gen rFIX manufactured
in a Chinese Hamster Ovary cell line without
exposure to human and animal proteins
Baxter Rixubis(previously
Bax 326)
FDA approval for pediatric treatment in
October 2014. Approved for adults in
US and Canada.
3rd generation rFIX
CSL Behring rIX FP‐ Applied for approval in 2015 rFIX is fused with recombinant human
albumin. Phase III trials showed a longer
half life‐
Novo Nordisk NN79 (N9 GP)‐ Marketing
authorizations submitted in 2015
Long-acting with reported half life of 93
hours
OPKO Health Factor IX CTP‐ Investigational New Drug (IND)
application submitted in Jan 2015
FIX fused with a carboxyl terminal peptide
to extend half-life

Access related Challenges
• High costs associated with safer treatments put them
out of the reach of patient populations particularly in
developing countries
• The access to treatments is also inhibited by supply
issues as drug manufacturers are not able to estimate
exact patient numbers
• Patients are sometimes rendered apprehensive about
using treatments due to the possibility of inhibitor
development which may increase long-term costs of
treatment
• The issue of developing inhibitors is something drug
manufacturers hope to address in new products
• Risks associated with transmission of blood borne
diseases through usage of human plasma concentrates
still remain a key factor though they are on the decline
2015

FUTURE OUTLOOK
2015

Future Outlook
• Haemophilia is a complicated orphan disease with life-long implications on the Quality-of-Life (QOL) of
patients, care-givers and communities
• Large parts of patient population remains undetected due to lack of proper diagnostic tests and
procedures
• Currently, there are no ground breaking treatments available in the market and even the ones that are
available are expensive for most patients in emerging market countries
• However, a lot of progress has happened in the treatment paradigm and there are a lot of new treatments
which are advancing through the pipeline, most notably are the genetic therapies used to treat the disease
• The biggest challenge for ensuring market access will be to make these newer treatments affordable for
vast majority of the patient populations
• While discovering and making medicines available is one part of the challenge, a lot needs to be done to
address unmet needs across the Haemophilia care continuum to improve outcomes
2015

Future Outlook – Emerging Markets Perspective
We have identified 5 such unmet needs – mostly in emerging markets, which if addressed, could
significantly improve outlook for patients, prescribers and communities
2015
Poor Diagnosis
Rates
Lack of Disease
Awareness
Lack of Training
and Medical
Expertise
Poor Market
Access
Lack of Data
Collection
Processes
1
2
3
4
5
◉ Poor rate of effectiveness of diagnostic tests and procedures is the biggest challenge in Hemophilia.
◉ This is even more important in emerging markets, like India, with large patient populations as poor rate of diagnosis leads
to wastage of important healthcare resources and deteriorates health outcomes
◉ Hemophilia is one such disease where very little has been done to identify and then treat patient populations in emerging
markets. We believe advocacy from relevant stakeholders in the healthcare system will lead to coordinated action by the
government to improve health outcomes
◉ This is one such area which can be addressed immediately as emerging market countries have large prescriber base with
strong focus on training. These countries need more disease awareness and disease management programs to better
manage the disease
◉ This has always been difficult in emerging markets as most treatments are rendered unaffordable due to economic
considerations. Companies and governments have to create incentives for working together either through innovative
pricing and access models or through effective risk sharing along patient pathways
◉ It is very important for pharmaceutical companies and patients to share outcomes data as it will ensure that newer
treatments are developed more effectively.

Market Access Overview in Hemophilia: Challenges and Opportunities

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