White paper

ORPHAN MEDICINES
LAUNCH EXCELLENCE
Sustaining launch success as Orphan Medicines come of age

By SARAH RICKWOOD, Vice President, European Thought Leadership, IQVIA

MAX NEWTON, Consultant, European Thought Leadership, IQVIA
TABLE OF CONTENTS

Introduction 1

The environment for Orphan Medicines comes of age 2

Orphan Medicines are a part of the continuum of specialty launches

which now dominate the global launch environment 2

Marketing authorisations for Orphan Medicines break records in 2018 3

From emergence to coming of age: what the future holds for Orphan Medicines 4

Ensuring Orphan Medicine Launch Excellence 6

What defines an excellent Orphan launch? 6

Foundational Launch Excellence success factors for Orphan Medicines 7

Special Launch Excellence success factors for Orphan Medicines 9

Structure and organisation of Orphan Medicines companies for Launch Excellence 16

Conclusion 18

References 19
INTRODUCTION

Launching Orphan Medicines excellently will become even more important over
the next 5 years. More patients with rare diseases have pharmacotherapies
available, and there are a growing number of disease-focussed registries,
increasing public and policy maker awareness, and significant R&D investment in
pharmacotherapies and in digital technologies to support trials and treatment.
A new frontier of challenge faces Orphan Medicines companies as the gap
between Orphan Medicines and mainstream specialty products narrows.
To understand how to succeed in launching an Orphan Medicine in the coming
years, companies must learn from past launches and apply an Orphan
Medicines-focused Launch Excellence framework for success.

Since 2007, IQVIA has identified the world’s most
commercially successful launches and researched the
success factors behind their Launch Excellence in a
series of influential white papers. These papers focused
1
on the key developed markets of the US, top 5 Europe
and Japan, but used as their starting point all innovative
branded launches. In a twenty-year period (1995–2015)
of launches, the nature of the launches coming to
market, and the ones which are most successful, has
changed dramatically. The first Launch Excellence study,
covering launches from 1995 to 2003, saw (by the IQVIA
measures of Launch Excellence) 28 excellent launches,
of which 82% were launches entering primary care
markets. By the fifth Launch Excellence study, covering
blockbusters for conditions with billions to hundreds
of millions of patients – the top selling product in the
world that year was the proton pump inhibitor Losec
(omeprazole). Since then, mainstream pharmaceutical
innovation has changed, dramatically fast – the top
two products by global sales (2018) are now Humira
(adalimumab), a monoclonal antibody for autoimmune
conditions, such as rheumatoid arthritis with a global
patient population estimated at 80m, and Revlimid
(lenalidomide), for multiple myeloma, myelodysplastic
syndrome and mantle cell lymphoma (with global
incidences each below 1m patients annually).
This IQVIA Orphan Medicine Launch Excellence

launches from 2011–2015, 87% of the 31 launches whitepaper covers the changing launch excellence

fulfilling our Excellence criteria were in specialty care.
When Orphan Medicine legislation was first introduced
in the US in 1983, the mainstream pharmaceutical
industry was ruled by primary care blockbusters –­the
world’s top selling launch was the H2 receptor antagonist
Tagamet (cimetidine). Even when European Orphan
Medicine legislation was enacted in 2000, the innovative
pharmaceutical market was still about primary care
paradigm, which will evolve as innovations for rare
diseases develop, drawing on case studies from across
the lifecycle of Orphan Medicines. The environment
for Orphan Medicines is moving into a new, more
competitive stage, and this will make it more challenging
for companies seeking to optimise their Orphan
Medicine launch. We outline the key areas of focus
for Orphan Medicines companies to address this
environment and prepare for an excellent launch.

iqviabiotech.com | 1
 THE ENVIRONMENT FOR ORPHAN It remains the case that only an estimated 5% of rare
diseases have an approved drug treatment. There’s
MEDICINES COMES OF AGE
still unmet medical need and a major opportunity to

Orphan Medicine legislation has expanded in the 36 commercialise innovative medicines, although not all the

years since pioneer legislation was introduced in the remaining 95% of untreated diseases may be druggable.

US. In addition to the major step of EU legislation in

Pharmaceutical manufacturers are faced with rising
2000, there are now initiatives, ranging from patient-
drug development costs. Relative to the cost of drug
and clinician-lead to formal legislation, for designating
development for traditional medicines, Orphan
medicines as Orphans and defining rare diseases
Medicine development costs ~30% of a non-Orphan
in Canada, Argentina, Peru, Colombia, Brazil, Japan,
Medicine3, and historically Orphan Medicine
Singapore, Taiwan, South Korea, China, Australia,
development have been more certain in terms of
New Zealand, Russia, Ukraine, and Kazakhstan.
getting an Orphan designated product to approval,

It remains the case that only an estimated 5% of rare
Figure 1: Rare disease statistics2
Between 6,000 and
8,000 distinct rare
diseases exist globally
although getting Orphan designation is tough. Falling
returns on investment for innovative medicines
globally makes Orphan Medicines an attractive
prospect for companies looking to launch an innovative
molecule in areas of high unmet need, one which is
6-8K increasingly aligned to the overall specialty direction
of the majority of the world’s largest pharmaceutical
companies’ portfolio.

ORPHAN MEDICINES ARE A PART OF THE

CONTINUUM OF SPECIALTY LAUNCHES
80% of rare diseases
have identified 80
80%% WHICH NOW DOMINATE THE GLOBAL LAUNCH
genetic origins ENVIRONMENT

Specialty medicines, as defined by IQVIA, are

medicines which meet at least five of eight specialty

30M people living in characteristics – a definition into which the great

Europe suffer from a
rare disease
50% of people
affected by rare
diseases are children
30M majority of Orphan Medicines comfortably sit.4 Over
the last decade, specialty has been the leading driver
of value growth in the global pharmaceutical market.
The speciality market has historically outgrown the
traditional medicines (defined as everything that is not
specialty) by 10.7% CAGR in the last 10 years. In 2018,
50% speciality medicines account for almost 40% of the list
price (pre-rebates and discounts) market value, a +16%
increase on the figure just 10 years previously (figure 2).

The specialty market will continue to grow because

Only ~5% of rare an increasing proportion of the global R&D pipeline
diseases have an
approved drug
~ 5% is devoted to these products, and most major
pharmaceutical companies either are, or a pivoting
treatment
strongly towards, being specialty-led companies.

2 | Orphan Medicines Launch Excellence: Sustaining launch success as Orphan Medicines come of age
Figure 2: Historical sales of speciality medicines have consistently outgrown traditional segment5
$994m
25% $945m
$918m
$873m
20% $793m 39%
$725m 35% 37%
$683m $694m 33%
15% $650m 31%
Growth rate (%)

$610m 28%
24% 25% 27%
23%
10%

5%
65% 63% 61%
69% 67%
77% 76% 75% 73% 72%
0%

-5%
2009 2010 2011 2012 2013 2014 2015 2016 2017 2018

Traditional growth rate Speciality growth rate Speciality sales Traditional sales

Source: IQVIA European Thought Leadership analysis, based on MIDAS data

This means specialty is becoming a very crowded

and competitive group of therapy areas. In this
Figure 3: FDA and EMA novel drug approvals are
context, Orphan Medicines are affected by some
now predominantly Orphan Medicines8
specialty trends – they are affected by increasing
competition for budgets that will grow slowly if at all. 59

As even mainstream specialty medicines are often

45 46
42%
now for extremely defined and quite limited patient 41

populations, the difference in patient population size

53% 61%
between mainstream and Orphan Medicines, although 59%
22
still present, narrows.
59% 58%
41% 47% 39%
MARKETING AUTHORISATIONS FOR ORPHAN 41%
MEDICINES BREAK RECORDS IN 2018 2014 2015 2016 2017 2018

FDA
2018 has been a record year for innovative medicines
42
in both the US and Europe with significant increases 40 39
35
to the numbers of new active substances approved.6 48%
58% 54% 27
The US saw a record breaking 59 approvals and the 46%
41%
EMA 42 marketing authorisations in the same period.
Both centralised authorities have seen an increase in 46% 54% 52%
42% 59%
both the numbers and proportion of Orphan Medicines
2014 2015 2016 2017 2018
approved in the past 5 years, with 2018 the first time
European Medicines Agency
that the FDA has approved more Orphan new active
substances than non-Orphan.7
Non-Orphan novel drug approvals
Orphan designated novel drug approvals
Source: European Medicine Agency, FDA

iqviabiotech.com | 3
 FROM EMERGENCE TO COMING OF
AGE: WHAT THE FUTURE HOLDS FOR
ORPHAN MEDICINES
Despite progress in the approval of new Orphan
Medicines, their coming of age poses three major
challenges:
1. I ncreasing profile of Orphan Medicine budget impact
Seven developed world markets, the US, top 5
Europe and Japan, account for over 85% of early
innovative launch medicine value and over 80%
of specialty medicine value (both pre-rebates and
discounts).9 Increasing numbers and focus by
manufacturers on rare diseases means growing
awareness and concern about the impact on
healthcare spend from Orphan Medicines. Some
of this concern is exaggerated: Orphan Medicines
remains a small minority of medicines spend (US
expenditure on Orphans was 10% of the total
US market in 2017 , and the most recent IQVIA
10
estimates of value share in Europe, with a different
Orphan Medicines definition, are even lower, at 3.5%
of European market value in 2016, a figure which is
very much in line with several other estimates cited
by EURORDIS11). While medicines with an extremely
high cost per patient make headlines, they are not
typical of most Orphan Medicines, the majority
of which in Europe are priced, at list, below €50k/
patient/year. All Orphan Medicines companies must
be aware of the payer and policy maker concern
about the impact Orphan Medicine spend has on
overall healthcare budgets, and be sensitive to
this, particularly because Orphan Medicines, by
the nature of the way they are developed and the
T
 he US is the key market for pharmacotherapeutic
innovation, and as such a bellwether for the reward
of Orphan Medicine innovation. The US has neither
national payers or Health Technology Assessment,
but payers have still moved to control Orphan
Medicines spend. Although non-coverage of Orphan
Medicines is still uncommon, coverage denials have
increased substantially in recent years, and other
trends include increase in patient cost sharing,
use of prior authorisation for products, and use of
quantity limits.12
2. More, more diverse players
As the number of Orphans approved has risen,
a wider variety of pharma companies have been
involved. Smaller biopharmaceutical companies
have found that if they have a strong Orphan
Medicine, they can commercialise themselves,
without partnering large pharma, because of lower
development costs, enhanced regulatory support,
and a limited number of countries to focus on
to realise full sales potential. However, while the
playing field is more level for smaller companies
to commercialise, there are also challenges.
Orphan Medicines can be subject to significant and
unpredictable delays to Market Access in certain
countries. Because a smaller number of countries
matter to the global roll-out of an Orphan launch,
these delays will matter more, and for a small
Figure 4: Companies submitting to health technology
appraisal in Europe are increasingly small and
medium sized companies13
20
20

evidence on which they are approved, may come

Companies submissions

to market with higher levels of uncertainty on 40%

15 14
efficacy. Orphan Medicines companies, individually
11
and collectively, must be clear about the facts on
10 9 50%
actual overall budgetary impact. Separately, they 27%
22% 35%
must ensure the equally important point on how the 11%
5 21% 55%
value of Orphan Medicines is evaluated, and the gap
67%
between regulatory and market access criteria is 29% 25%
18%
recognised and constructively addressed by payers, 0
2012 2014 2016 2018
health technology assessors and regulators. Small Medium Top-20

Source: IQVIA HTA Accelerator, European Thought Leadership analysis

4 | Orphan Medicines Launch Excellence: Sustaining launch success as Orphan Medicines come of age
 Biotech company which lacks the deep pockets
and pre-existing product income streams of
large pharma, they can prove especially painful.
Orphan Medicines may require lower levels of
commercialisation investment in terms of gross
spend and full-time equivalents (FTEs), but they
will demand much more in terms of expertise,
specialisms and complexity management.
3. G
 rowing competition: between and within Orphan
disease areas, and genericisations
The initial premise of Orphan Medicines was that
they would be treating populations with no existing
pharmacotherapy and a high unmet need, where the
commercial incentive to develop was inherently low.
Whilst the absolute share of all Orphan diseases
which have existing pharmacotherapies remains
low, the fact is the realised pharmacotherapy market
is now more crowded, with competition between
pharmacotherapies within a given rare disease a
growing possibility. Loss of Orphan designation for
earlier Orphan launches, patent expiries, and, in
some areas, the availability of generic (and possibly
in the future biosimilar) medicines have contributed
to the maturation of a range of Orphan disease
areas. Payer and Health Technology Assessor
expectations of what constitutes a truly unique,
Figure 5: Multiple competitors are entering some rare diseases14
SMA affects a 1 in 6,000 live births however,
has many treatments in development
Non-genetic therapies Genetic therapies
Modulate SMN2 expression Replaces defective SMN1 gene
SPINRAZA (Biogen / lonis) AVXS-101 (AveXis)
Branaplam (Novartis)
Risdiplam (Roche)
Activate troponin
(Cytokinetics/
Reldesemtiv
Astellas Pharma)
Marketed In clinical development
Source: IQVIA Consulting Group analysis
powerful and pertinent value proposition for a new
Orphan Medicine have shifted, as a result for some
rare diseases of maturation and because of the
pressures on other parts of the Medicine budget.
T
 he first Orphan Medicines ever available to
treat a given rare disease were undoubtedly
differentiated, but for some rare diseases and some
Orphan Medicines the absolute clinical benefit
brought was low. In other cases, the first agent
was introduced many years ago and has now been
joined by other treatments either of the same or
alternative types. An example would be Gauchers
disease type 1, where three enzyme replacement
therapies exist: Cerezyme (imiglucerase), the first
ERT, launched more than 20 years ago, and the more
recently launched products VPRIV (Velaglucerase)
and Elelyso (taliglucerase). In addition to these
treatments, certain types of Gauchers type 1
patients can be treated with one of two Substrate
Reduction Therapies, Cerdelga (eliglustat) or Zavesca
(miglustat). Other rare disease areas, as in the case
of Spinal Muscular Atrophy (SMA) and Haemophilia,
are seeing a burst of promising innovative therapies
in development or on the market, as outlined in the
graphic below.
Several therapies are in the pipeline for Haemophilia B,
which affects 1 in 25,000 live male births
Genetic therapies
DTX101 (Dimension Therapeutics)
SB-FIX (Sangamo Therapeutics)
AMT-060 (UniQure)
SPK-FIX (Spark Therapeutics/Pfizer)
Injectable Oral Solid Genetic Therapy
iqviabiotech.com | 5
 Orphan Medicines markets in both the US and Europe
have been established for sufficiently long that generic
competition is, for some products, a possibility. An
IQVIA Institute study noted that in the US, of all 503
medicines which had received a US Orphan Medicine
designation, 217 were no longer protected by either
Orphan exclusivity or patents, and as of June 2018
116 of those drugs faced generic competitors. 15
Biosimilars are now widely accepted outside rare
diseases; it is conceivable that when available they
will be acceptable for rare diseases as well. Soliris
(eculizumab), an Orphan biologic to treat paroxysmal
nocturnal haemoglobinuria, is reported to have
multiple biosimilars developed in anticipation of its
loss of exclusivity.
ENSURING ORPHAN MEDICINE
LAUNCH EXCELLENCE
In a pharmaceutical market where specialty innovation
is the mainstream, the foundational success factors of
Excellence for mainstream launches are also entirely
relevant to Orphan Medicines. Therefore, alongside
the standarised launch excellence criteria, there are
additional specific areas of focus for Orphan Medicines
to succeed.
WHAT DEFINES AN EXCELLENT ORPHAN LAUNCH?
2. Optimal market access for the product
Orphan Medicine launches are much more diverse
than mainstream launches. The definition of an Orphan
Medicine varies according to regulatory regime. The
conditions, patients and their circumstances are highly
diverse, as rarity is the main common factor. Even
though there are more Orphan Medicine approvals
3. O
than ever before, there are still a much smaller number
of Orphan Medicines that either are or have been
on the market than mainstream drugs. Therefore,
a simple quantitative set of measures for Launch
Excellence is not appropriate. Instead, we argue that
whether an Orphan launch is Excellent or not is about
whether the company developing and launching the
medicine has performed well on the following three
tasks:
6 | Orphan Medicines Launch Excellence: Sustaining launch success as Orphan Medicines come of age
1. C
 linical development effectiveness, and label
Getting an optimal label approved, reflecting the
clinical potential of the product, in a timely and
efficient fashion. The first challenge is to achieve
Orphan Medicine designation for development and
then approval with a label which is appropriate to
the patient population that could benefit from the
product, across the different regulatory regimes.
It is not necessarily straightforward or easy to
obtain Orphan designation in the first instance:
from all Orphan designation applications submitted
to the Committee for Orphan Medicinal Products
(COMP) at the EMA, only 72% receive a positive
opinion for designation. Amongst the products
designated based on a potential significant benefit
over an existing treatment, 27% more will be losing
their Orphan status at the time of receiving their
marketing authorisation.16
C
 linical development and label effectiveness can
further be broken down into:
• D
 esigning the trial with the right clinical endpoints
– which need to be patient appropriate and
payer relevant
• R
 ecruiting the right patients for the trial in a
timely and cost-effective fashion.
Market access for the label population, at an
acceptable price requires successful navigation of
multiple market access environments – international,
national and local. Excellence (as in market access for
the full label population) is increasingly challenging.
 ptimal product uptake for the approved,
market accessible population
Excellence means accurately finding the patients,
supporting physician awareness of the product, and
generating the uptake of the product in line with the
estimated patient population.
FOUNDATIONAL LAUNCH EXCELLENCE SUCCESS
FACTORS FOR ORPHAN MEDICINES
Powerful and pertinent value proposition
Innovative pharmaceutical companies aspire to
launch products offering differentiated value
in areas of unmet need. For Orphan Medicine
launches, categorisation into the high unmet need,
high differentiation group is common, but it is
not automatic. Building a powerful and pertinent
value proposition for an Orphan Medicine launch
is, therefore, more important than ever. Orphan
designation alone does not confer a strong value
proposition. Companies must follow a three-point
approach to building and reinforcing their value
proposition.
• Start early, and get clinical endpoints that are
informed by, and relevant to patients as well as
payers and prescribers. As soon as the medicine
moves into Phase II, companies must invest in
directly understanding the payer, patient and
competitive environment as it is, and is likely to
be when the product comes to market. Start-up
companies, especially, may be completely unused to
early research into patient need, payer environment
and commercial concerns and tempted to postpone
what seems unnecessary effort and expense in
favour of clinical focus. This is false economy; patient
and payer insights collected now may be able to
be built more easily into trial design. If approval is
speeded up, as can happen for Orphan Medicines,
companies which postpone their payer research and
dossier preparation could be caught out.
• Research externally, and directly with patients
and payers. Companies should not rely only on
perspective filtered through Key Opinion Leaders or
Patient Organisations. As an example, in Duchenne
Muscular Dystrophy, focus on the six-minute walk
test as a primary trial endpoint proved impossible
for all but younger patients with existing strong
walking ability. This limited the pool of patients for
trials, reduced the number of centres that could be
involved (as the test was complex to administer) and
set an unrealistic bar for efficacy. All of these issues
could have been surfaced and addressed earlier with
appropriate research and consultation.
• P
 lan broadly. Regulatory and health technology
assessment can be based on a wide variety of
inputs, so plan to build collecting these into the
development programme from the start – they will
make up a more detailed, broader basis for a value
submission and provide more degrees of freedom in
building value arguments later. Real world evidence
will increasingly be required for Orphan Medicines
and across a broader spectrum of what constitutes
RWE, as this expands at the “hard data” end into
genomics, and at the softer end into device driven
and other digital data. Country initiatives such as
Genomics England’s 100,000 genome project have
been pioneered for rare diseases. As this data
becomes more available, for example, via IQVIA’s
partnership with Genomics England to develop a
real-world research platform,17 it will also be more
expected.
Effective and efficient stakeholder engagement
Effective Stakeholder engagement starts with
mapping out, in detail, by country, who an Orphan
Medicine’s stakeholders, and the influencers of those
stakeholder, are. For Orphan Medicines, as for all
specialty products, Stakeholder maps will be complex.
Companies must avoid the error of presuming that
their scientific and clinical stakeholders are the only
ones which matter – or the only ones which need be
Building a powerful and pertinent
value proposition for an Orphan
Medicine launch is, therefore,
more important than ever. Orphan
designation alone does not confer a
strong value proposition.
iqviabiotech.com | 7
 engaged early. Engage with patients, payers, policy
makers and healthcare providers to understand their
current knowledge of and involvement with a given
rare disease. Patient groups are also as important
a stakeholder group as the others, and require
appropriate and compliant engagement.
Even with an early start and effective investment
levels for an Orphan Medicine companies need
to be prepared – and prepare their investors and
stakeholders for – a long journey with unexpected
delays. An example is the journey that BioMarin, a
pharmaceutical company established for 20 years
and with seven marketed medicines, took with
their medicine Vimizim (elosulfase alfa) for Morquio
syndrome. This medicine received a Marketing
Authorisation on the 28th of April 2014. The UK was
the major country involved in the clinical development
of Vimizim – just over 28% of worldwide trial patients
were in English trial sites, and the first patient
dosed in the world was also located in England.
Nevertheless, the journey to market access took
almost two years, and over twenty stages of meetings,
submissions, clarifications, revisions, stakeholder
engagements, with final approval in January 2016.
In such circumstances, companies require strong
commitment and dedication internally, but also
extremely strong communication and relationship
building externally, not just with the market access and
A company’s alignment around a
launch, meaning clarity on what
to achieve for launch success,
and how to achieve it across
functions and between countries,
is the single most important factor
differentiating Excellent from less
successful launches.
8 | Orphan Medicines Launch Excellence: Sustaining launch success as Orphan Medicines come of age
health technology assessment bodies, but with patient
groups, clinicians and policy makers. For patients
especially, market access delays are hugely frustrating.
The pharmaceutical company must educate and
communicate actively and effectively on the market
access process and their activities to address it.
Alignment and preparation
Although it sounds obvious and intangible, a
company’s alignment around a launch, meaning clarity
on what to achieve for launch success, and how to
achieve it across functions and between countries,
is the single most important factor differentiating
Excellent from less successful launches.
For Orphan Medicines, this is no different, and in some
ways, alignment should be easier to achieve – in a small
company or for a very small patient group in a limited
number of countries. This does not, however, mean it is
automatic, nor does it mean this foundational success
factor can be neglected. If, for example, commercial
and market access functions are not invested in
sufficiently early or fail to have an adequate voice in
the preparation of the launch, there will be a lack of
alignment, and inadequate preparation for launch.
There are Orphan Medicine preparation challenges,
when, for example, a product gets approval on early
stage trials or has enormously extended access
discussions – timelines can be very unpredictable.
Preparation must be flexible, and prepared to use
external support when necessary to improve the
speed with which activity can be dialled up or down
in response to changing conditions. Companies
embarking on their first launch may find the number
and detail of preparation activities a daunting prospect
– the IQVIA launch preparation framework, for
example, covers 57 areas of launch preparation activity
across the three foundational launch success factors.
However, the key to effective and aligned Launch
Excellence preparation is understanding the critical
success factors for a given launch – whilst all the other
activities still need to be addressed, these critical
success factors take priority.
SPECIAL LAUNCH EXCELLENCE SUCCESS FACTORS
FOR ORPHAN MEDICINES
Patient centricity
Partnering with patients, their carers, support groups
and advocates has always been a crucial activity for
Orphan Medicines manufacturers. This engagement, if
effective, can also help address some of the challenges
of developing Orphan Medicines, including appropriate
and effective clinical trial design and execution,
and ensuring medicines get to the right patients.
Relationships with patients, families and patient
advocates are one of the most important investments
an Orphan Medicines company will make during the
development and launch of their product. Excellent
Orphan Medicine launches will be ones where the
company ensures this investment is:
• Early and appropriate
• Listening-led
• Consistent and long term
• Honest and clear.
As IQVIA has elaborated in a blog on engaging
with patients and their families for rare diseases,18
working with patients, patient advocacy groups, and
communities can help with trial recruitment in many
ways:
1. Patient, carer and patient group involvement
can help design a trial that is clinically relevant to
patients, ensuring that the study is feasible as well
as fulfilling regulatory requirements. This means
understanding how to avoid the trial too great
an impact on school, work and family life, by, for
example, minimising visits and interventions and
reducing travel for patients – whilst continuing to
collect the optimal level of data. Digital technologies
enabling remote data capture will become
increasingly useful.
2. Patients are also the best partners to find trial
recruits. Websites, mobile apps and social media can
also help patients find the studies and sites and see
how they can be involved. Patient groups can also
help to educate study sites and investigators about
the disease – for example, on the patient pathway
and the most effective way to communicate with
patients on the possibility of joining trials, and to
continue engagement throughout the trial.
Patient-centricity should extend to international
organisation. In the European Union, since 2016,
24 European Reference Networks (ERNs) have been
established, each around a group of similar disorders
– for example, metabERN, the European Reference
Network on hereditary metabolic disorders. The 24
ERNs involve over 900 specialist units in over 300
hospitals across 26 countries. The patient-centric
principle is that although patients within the EU can
cross borders to receive healthcare, wherever possible,
expertise and specialists should come to the patient,
using telehealth/digital technologies to make this
more effective. As an example, the stated role of the
metabERN European Reference network is to “develop
a real-time consultation platform for clinical decision
– making processes and foster translational research
programmes across Inherited Metabolic Diseases” .19
Pharmaceutical companies bringing Orphan Medicines
to the European markets needs to understand and
engage with these international organisations, early.
They also need to understand how they might evolve.
The UK has been historically involved in 23 out of 24
of the ERNs, and led six of them. As a preparation for
BREXIT, the European Commission asked UK hospitals
leading ERNs to step down, and future involvement of
the UK is currently uncertain. Given the advantages
of pooling data, expertise and patient resources that
multicountry entities provide, this is a retrograde step
for both the UK and the EU.
iqviabiotech.com | 9
 Payer environment and affordability
Orphan Medicines are no longer shielded from the
payer pressures which affect mainstream products.
Three examples of how the environment has changed:
1. Move Orphan Medicines into the mainstream HTA
process. In Germany, the initial guiding principle
for Orphan Medicines was that Orphan designation
alone was proof of added benefit. This limited
IQWIG, the German Health Technology assessor,
to an assessment of information provided by the
pharmaceutical companies on the number of
affected patients and the cost of treatment. Now,
if cost of treatment exceeds a yearly turnover limit
of 50 million euros in statutory health insurance,
the Orphan Medicine enters the regular procedure
of early benefit assessment. The first Orphan
Medicine, Jakavi (ruxolitinib) for myelofibrosis, to
exceed the threshold did so in 2013.
2. Share information, assessment and negotiation
on Orphans: The BENELUXA initiative, founded by
Belgium, Netherlands, Luxembourg and Austria,
and now, as of mid-2018, joined by Ireland, seeks to
pool information in the form of horizon scanning,
Health Technology Assessment capabilities beyond
those of the national members, and negotiating
power for products- with a focus (non-exclusive) on
Orphan Medicines. Pharmaceutical companies are
invited to enter a pilot process for joint assessment
and negotiation. Thus far, Orphan and non-Orphan
products have been subject to information sharing
and in some cases joint assessment by BENELUXA –
While the market access landscape
is challenging for all Orphan
Medicines, it is particularly
challenging for those that are
advanced therapies, mostly cell and
gene therapies.
10 | Orphan Medicines Launch Excellence: Sustaining launch success as Orphan Medicines come of age
Orkambi (Lumacaftor/ivacaftor), for cystic fibrosis,
which was turned down, Vyndaqel for amyloidosis,
and Lojuxta (Lomitapide) a rare disease medicine
authorised under “special circumstances”, Ocaliva
(obeticholic acid) for primary biliary cholangitis,
Xermelo (telotristat ethyl) for carcinoid syndrome,
Ravicti (Glycerol phenylbutyrate) for Urea cycle
disorders, and Spinraza (nusinersen) for Spinal
muscular dystrophy, which was also subject to join
negotiations by Belgium and the Netherlands.
3. Health Technology assessment initiatives in
the US via ICER starting the development of an
Orphan Medicine Value Assessment Framework
and pricing methodology for Orphan Medicines.
The US is the largest market for Orphan Medicines
and does not have formal, national Health
Technology Assessment processes. ICER (the
Institute for Clinical and Economic Review) is a
private foundation which has gained influence in
health technology assessment, although it should
be noted that in the field of Orphan Medicines its
proposals have met with pushback from some
Orphan Medicine manufacturers. ICER has active
programmes of assessment for Orphan Medicine
areas such as Duchenne Muscular Dystrophy.
Orphan Medicine unique points: alternative funding
models may be increasingly considered
While the market access landscape is challenging for
all Orphan Medicines, it is particularly challenging for
those that are advanced therapies, mostly cell and
gene therapies. IQVIA, in collaboration with the ARM
Foundation for Cell and Gene Medicine, published
the first Economic Impact landscape analysis of
regenerative medicine and advanced therapy in 2018.20
This study of published academic literature, health
technology assessments, and value frameworks
related to the global health economic impact of cell
and gene therapies showed these therapies, many of
which are Orphan Medicines, struggled to meet the
current requirements for successful Health Technology
Assessments, and there is currently an unclear market
access landscape.
While innovative contracting and funding have been challenging for all medicines, but Orphan Medicines
explored as market access tools for more than 20 have been subject to some of the longest delays to
years, these agreements have been less than optimal, access of all medicines, and their slow and sometimes
only reluctantly considered by payers, who have seen uncertain progress through market access contrasts
them as bureaucratic and often showing bias towards with often more straightforward progress to approval.
one partner. Increased scrutiny on Orphan therapies, Availability across Europe for Orphan Medicines
especially new gene and cell therapies, and even more highlights the issues facing Orphan Medicines
stringent healthcare budgets means future finance
following marketing authorisation. While all products
agreements need to be evenly weighted, providing
within the study cohort have achieved EMA marketing
more mutual benefit for both payer and manufacturer.
authorisation, there is a high degree of variability versus
While nascent, approached to evaluating the value
non-Orphan new active substance group (figure 6).
of curative gene therapies are now being developed,
with ICER collaborating with NICE and with Canadian The creation of accelerated pathways through the
Agency for Drugs and Technologies in Health (CADTH) regulatory system of the FDA and EMA has created
on approaches to assessing the value of curative gene significant issues for payers. Approval of Orphan
therapies – which often will be Orphan. Medicines on surrogate endpoints and phase-II trial
data speeds products to approval but not necessarily
Successfully addressing the market access
to access – the evidence requirements of payers and
environment at both national and subnational levels
Orphan designation and marketing authorisation regulators are misaligned. Requirement to show

from EMA, FDA or other regulators is only the first efficacy and safety versus cost-effectiveness is now

stage in a series of significant hurdles for Orphan broadening as the threshold for evidence is yet to
Medicines. Successful navigation of the Health be adjusted by major HTA bodies to approve such
Technology Appraisal (HTA) environment is the next medicines. No HTA body has yet employed a simplified
hurdle for launch excellence in Orphan Medicines. The HTA route for rare disease medicines, and the often
market access environment is, of course, increasingly cited Highly Specialised Technology (HST) route by

Figure 6: Products with marketing authorisation have variance in availability across Europe21
100
% of products with sales (2005-2017)

90
80
70
60
50
40
30
20
10
0
Y

CE

AY

EN

AL

IA

IA

IA

IA

IA

IA
D
AN

AL

AR
U

AR
RI

KI
N

AN
EC
AI

IU

AT

AN

AN

AR

TV
G
AN

RW

N
ED

LA

LA
VA
ST

IT

SP

VE

G
M

CZ
M

LG

LA

EL

LA
O

LG
M

U
N
FR

SW

RT

PO
AU

EN

O
ER

CR

TH
ER

IR
BE

RO
U
FI

BU
N

SL
SL
PO

H
G

LI
ET
N

Orphan new active substances Non-Orphan new active substance (NAS)

Source: IQVIA MIDAS, European Thought Leadership analysis

iqviabiotech.com | 11
 NICE caters to ultra-Orphan Medicines only, an average
of three per year. Health Technology Assessors are
giving negative or restricted decisions on a growing
proportion of new Orphan Medicines in Germany, Spain
and France – the UK was the only exception to this trend.
There’s need for a consistent, bespoke approach to
Orphan drug appraisals. There is significant variability
across the major European HTA bodies, and access
within countries is also often variable. Previous
analyses run by IQVIA 23 highlight the differences

Figure 7: The growing restrictions from HTA bodies in Europe increasingly impact Orphan Medicines22
Orphan Designated Drug HTA Outcomes (2013-2018)
N=54 N=101 N=63 N=137 N=24 N=65
100%

80% 43% 47%

60% 79% 72%

93% 83%

40% 35% 22%

20% 18%
12% 31%
22% 8%
4%
4% 9% 8% 9%
0%
2013-2015 2016-2018 2013-2015 2016-2018 2013-2015 2016-2018

Positive outcome Restrictive outcome Negative outcome

* Positive = full access as per label; Restricted = access but with label restrictions; negative = no access granted.
** This analysis includes treatments with orphan status across all therapeutic areas with completed and published health technology assessments
in France, Germany and the UK between 2013 and 2018. Note: UK = SMC, AWMSG, and NICE; France covers ASMR I to ASMR V ratings.

Source: IQVIA HTA Accelerator, European Thought Leadership analysis

Figure 8: The process for reviewing an Orphan Medicine varies from the traditional process as well
as internationally24

HTA data • No need for health economics data l l l No Info X

package • Surrogate endpoints accepted l l l l l
requirements
• Flexibility towards Phase II data and small trials l l l l l
HTA • Simplified process X l X X X
processes
• Shorter timelines l X X l X

HTA • Automatic additional benefits (national) X l X X X

outcomes
• Allowances regarding pricing outcomes X l l l l
Funding • e.g.: exemption of tax, additional funding l X X l X

X No Benefit l Informal or limited Benefit l Formal Benefits

Source: IQVIA HTA Accelerator, European Thought Leadership analysis

12 | Orphan Medicines Launch Excellence: Sustaining launch success as Orphan Medicines come of age
between access within England and the devolved
nations (Scotland, Wales, Northern Ireland). Between
England and the devolved nations, a difference of
14% in the number of Orphan Medicines available to
patients exists. In the enzyme-replacement therapy
Addressing the challenge of greater market
access barriers
Greater market access barriers for Orphan Medicines
are, unfortunately inevitable. Companies developing
these medicines must be proactive at an early stage:

(ERT) class of Orphan Medicines, only 3/8 medicines • C

received recommendations across all 4 nations.
Focussing on the mature European HTA bodies (HAS
in France; G-BA in Germany; and NICE in England) very
few launches (11%) achieved excellence in terms of
unrestricted positive appraisal, notably brands such
as: Rydapt, Yervoy, Galafold, Ocaliva, Farydak, Iclusig,
Translarna, Imbruvica, and Vimizim by achieving
recommendation across all EU3 HTA bodies with the
original submission between 2010-2018. Of these
products, Rydapt (midostaurin) is the only one to
submit to all the HTA bodies using supporting RWE.
Usage of RWE to support HTA submissions were
highly beneficial within the HTA setting, with only 9%
of submissions with HTA not receiving a positive, or
positive with restrictions decision at HTA.
 onsult patients, payers and health technology
assessors at the earliest possible stage in clinical
development. Hire (internally or third party) experts
to enable these discussions and interpret their
outcome into recommendations for the clinical and
real-world data development of the product. Payers
increasingly have long range horizon scanning
programmes to understand the products which
they may have to budget for in the future. In some
countries, the UK as an example, the plan is that this
horizon scanning will look as early as Phase I/II. Not
as many companies have submitted information
on their products to such early horizon scanning
programmes as could have, meaning they miss out
on the opportunity to have their product early on a
payer’s radar and benefit from early feedback and
advice on product value proposition acceptability.
Invest in this early engagement.

Figure 9: EU3 HTA decisions show few excellent launches in Orphan Medicines25

Rejected despite Positive with …positive 47

RWE restrictions and recommendation
RWE submission and RWE submission
Small 18

Medium 13
9% 30% 61%
Top-20 16

Excellent launch using

RWE in HTA
LAUNCH EXCELLENCE
9

Small 5
0% 57% 39% 11%
Medium 1

Market access Market access Market access Market access Top-20 3

recommendation in recommendation in recommendation in recommendation in
none of the EU just 1 EU3 market 2/3 of the EU3 all 3 countries
Excellent launches in HTA

Source: IQVIA HTA Accelerator, European Thought Leadership analysis

iqviabiotech.com | 13
 • Build an early understanding of market access
environment across all major markets, not just
the US. In practice, this means the UK, Germany,
France, Italy and Spain in addition to the US. The US
will, inevitably be the first launch market for most
Orphan Medicines, and will account for a significant
share, possibly the majority, of revenues. However,
Europe will be the second market block for almost
all Orphan Medicines, and most European countries
may in fact require earlier market access insight and
planning than the US. Even if a first launch in US is
planned, do not postpone development of European
market access insight and engagement.
• Recognise the reality of budget limitations and
aim to be involved in shaping the debate on
Orphan Medicines value assessment. Payers no
longer consider spend on an Orphan Medicine
in isolation to the other calls on their medicines
budget. Orphan Medicines companies should
not expect them to do so. Have a dialogue
which acknowledges the choices which payers
must make, and which makes constructive
contributions to the ongoing debate about costs
and affordability of Orphan Medicines. This may
include understanding and acknowledging the
ancillary costs of pharmacotherapeutic treatment
(for example hospital visits, counselling and patient
support, adjunct therapies) and even the long-term
consequences and costs of curative or disease
modifying therapies. Companies can be on the front
foot on this: as an example, the CEOs of Bluebird
Bio and Spark therapeutics jointly authored a Health
Affairs white paper in 2017 discussing possible value
frameworks for gene therapies.26

Figure 10: Advanced analytics in practice supports Orphan Medicines to maximise patient cohorts27

Potential Patient Pool

226%
• G
 lobal study of rare form Patient access
of blindness
• Cross-border referrals
Potential Patients

coordinated with sponsor

• M
 ulti-channel efforts
leverage sponsor,
advocacy, and investigator
• P
 ublic registry data: 500 neuro-
relationships
ophthalmologists, no validation of
• P
 ublic physician registry data
active patients
confirms engaged specialists,
but lacks insight on patient
• R
 eal world data (Rx / claims): 60 neuro-
activity
Traditional Data-Driven ophthalmologists, active patients last
• U
 nmet need for treatment Method Method 12 months
options generating high level
of physician interest

19% physicians 29 patients 19 patients enrolled from

physician referral sources
approached have referred
agreed to refer to date 41% enrolled patients (US)

Source: IQVIA Analytics Centre of Excellence

Note: Numbers are not finalised as study is on-going

14 | Orphan Medicines Launch Excellence: Sustaining launch success as Orphan Medicines come of age
Patient identification in clinical trial recruitment and
in post approval treatment
An oft-quoted number in rare diseases is 4.8 years
– one estimate of the average time it takes a patient
suffering from a rare disease to receive appropriate
diagnosis and treatment. Of course, in fact, times to
effective diagnosis and treatment for rare diseases
vary hugely – from pre- or neonatal diagnosis to never.
Nevertheless, rare diseases are less likely to be well
and rapidly diagnosed – because most non-specialist
healthcare professionals will see a given rare disease
once or twice in their professional careers, if at all, and
because apart from a few high-profile conditions, most
rare diseases and their symptomatology are neither
well known, or routinely screened for.
Advanced analytics in clinical trial recruitment
For clinical trials in rare diseases, patient recruitment
is often very difficult. The combination of few,
geographically dispersed patients, few if any dedicated
treatment facilities, and very small numbers of
healthcare professionals who are expert means
identification of centres and clinical trial candidates
is challenging. For Orphan Medicines, Excellence in
clinical trials is vital to Launch Excellence as a whole.
Better use of healthcare system data, via advanced
analytics, can speed and improve the accuracy of site
selection and patient recruitment.
As an example, IQVIA leveraged existing data sources
in a novel approach to boost patient enrolment in
a trial for a rare form of blindness. In this condition
the challenge was finding US specialists who were
currently treating patients, a minority of all the
specialists who could potentially be involved.
Using physician registry data, specialists who were
particularly engaged with the therapy area, could be
identified, but this did not provide insight into their
recent patient activity. To find the physicians with
both the specialism and current patients, IQVIA used
real-world prescription and claims data to filter on
physicians that had seen an active patient in the last
year. This helped concentrate the contact list to the top
10–12% of physicians. Through this data-driven referral
support, 19% of all contacted physicians agreed to
refer patients to the investigator site, with 29 patients
referred. Ultimately this produced 19 patients enrolled
to the study, 41% of the total patients enrolled.
Machine learning in prospective patient
identification
Better use of existing healthcare system data,
combined with advanced analytics is also a powerful
too when an Orphan Medicine has been approved,
with market access granted, and the third Launch
Excellence challenge is to generate the optimum
level of uptake. To do this, there is again the two-fold
challenge of finding physicians and finding patients.
For an ultra-rare neuromuscular disorder in the US,
characterised by under-diagnosis due to slow disease
progression and complex presentation, there were
very few known patients according to claims data, and
standard prescription data sources were not actually
useful in identifying the physicians who might treat
patients. IQVIA used the data that was available on
existing patients to teach a machine learning algorithm
to identify potential at-risk patients. When this
algorithm was run on the wider set of all claims data,
which contained about 1,500 pre-identified disease
sufferers, it identified about 4,700 patients who were
highly likely to be undiagnosed sufferers of the same
condition. It was then possible to link these “at risk”
patients to physicians to provide an alert to review
those patients as potential sufferers of the disorder–
an as an ongoing service, provide new potential patient
alerts as they emerged from new claims data.
Patient registries
The detail and scope of patient and physician data
varies by country, and what is possible in the US
may not be possible in the same way in Europe, but
the principle remains: what already exists in terms
of healthcare system data on rare diseases is often
under-utilised, and advanced analytical techniques,
iqviabiotech.com | 15
 such as machine learning, can enable better
identification of potential patients and link them better
to physicians and centres. To do this optimally, these
tools need as much high-quality data as possible on
the existing patient pools. This requires effective,
and preferably extensive patient registries for the
rare disease.
Patient registries in rare diseases are evolving – but
there are a very limited number of international
registries which exist due to limited funding. In a
recent study in the European Union, 747 rare disease
registries were counted, of which 69% were national
only, 10% regional, 8% European, and 13% were
global. This needs to change; as rare diseases have
28
very few patients, local or single country efforts to
recruit patients for trials are slow and can fail simply
because of the very small numbers of patients in the
pool, who may be further reduced by the inclusion/
exclusion criteria for trials or other barriers.
Rare disease registries are founded with a range of
aims, including better understanding of the natural
history and outcomes of the disease (by identifying
patients and following them over time), connecting
patients, healthcare professionals and caregivers,
and supporting research on the genetic, molecular
and physiological basis of the disease. Lastly, very
importantly for Orphan Medicines companies, patient
registries establish a patient basis for evaluating new
medicines.29 An example of the breadth of data that
Orphan Medicines companies are
a highly diverse group, from top
20 pharmaceutical companies for
which Orphan Medicines are a
division/acquisition to Biotech start-
ups for which an Orphan Medicine
is the sole commercialised product.
16 | Orphan Medicines Launch Excellence: Sustaining launch success as Orphan Medicines come of age
a well-established patient registry can provide is that
of the Cystic Fibrosis Foundation Registry Program
in the US. This registry was initiated in the 1960s and
currently has active records of 29,000 patients, or 84%
of all CF patients in the US.
IQVIA’s recent white paper on Patient Registries
sees huge potential in registries improving the
development of therapies for rare diseases, and this
progress will be enabled by new technologies which
make it easier to aggregate the clinically rich type of
data that is required to drive more effective clinical
trial design, and also the development of better
ways to identify patients for treatment. Most patient
registries are currently public and established by
academic institutions – in Europe, an Orphanet Survey
established that 84% of registries identified fitted this
description. 30 Pharmaceutical companies must work
with academic institutions, patient groups and others
in building patient registries.
STRUCTURE AND ORGANISATION OF ORPHAN
MEDICINES COMPANIES FOR LAUNCH EXCELLENCE
As noted earlier, Orphan Medicines companies are
a highly diverse group, from top 20 pharmaceutical
companies for which Orphan Medicines are a
division/acquisition to Biotech start-ups for which an
Orphan Medicine is the sole commercialised product.
Unsurprisingly, the organisations behind the launch
of Orphan Medicines are diverse, ranging from
centralised, international HQ driven operations to
more country driven operations. There, however,
are commonalities.
Geographic focus and reach
Broad, national coverage of healthcare
professionals in terms of face to face engagement
isn’t necessarily required or sustainable – spend
time getting the right focus for engagement and align
resource accordingly. This may mean teams that work
both nationally and internationally, as they align with
the increasingly international nature of clinical, payer
and patient networks for rare diseases – for example,
the European Reference Networks.
Communication and stakeholder engagement
Building alternative (often digital) communication
channels is key to expand reach and build awareness
and knowledge beyond the healthcare professionals
and centres that are the core focus. It is also more
cost effective and appropriate for today’s specialty
healthcare environment. IQVIA’s previous research
shows that mainstream commercially successful
specialty launches have a significantly higher share of
promotional activity that is digital in the first year of
launch in each of US, top 5 Europe, Japan. This result
31
is likely to apply to Orphan Medicines as well.
Ensuring rare disease information resources
are comprehensive and well resourced. Digital
communication is an important tool to ensure the
wider audience of healthcare professionals gets the
information they need to be part of rare disease
diagnosis, treatment or support programmes. It is
also crucial for patients and their carers. Patients and
families often report they get very little information
about their rare condition, and not only have to
research it for themselves, but also for the non-
specialist healthcare professionals who interact with
them. Orphan Medicine companies should support the
creation and dissemination of effective information
resource, and must be creative in thinking how these
should be disseminated. For example, for young
children, information on their condition in cartoon
format might be more effective than information
leaflets, and welcomed by parents.
A Medical Affairs Launch Excellence plan
With the rise of specialty launches, Medical
Affairs has become an increasingly important
function for many pharmaceutical companies.
For Orphan Medicines companies, it is absolutely
vital, given that, especially for breakthrough Orphan
Medicines clinical networks will initially be weak, and
healthcare professional knowledge low. The Medical
Affairs function of Orphan Medicine companies must
be established early in the launch planning and
preparation process. Dedicated global medical roles
should be assigned at the start of phase III, typically
3–5 years prior to launch, and dedicated local medical
leadership roles should be resourced 2–3 years prior
to launch. Local Medical Science Liaisons (MSLs)
should be in place ~24–18 months prior to launch. A
robust governance framework should be established
right at the start to ensure that compliance on ethical
standards and the separation of promotional and MSL
activity is clear. Companies must also have a long term,
strategic plan for MSLs that reflects the stage of clinical
development and launch preparation of the product,
with the most useful and relevant Medical activities.
Account management and field-based roles
Orphan Medicine launches do not need high head
count for the commercial and medical function
but do need the right mix of skills and effective
teamwork – for a single major country, between
5 and 30 full time equivalents may be ample, with
key account managers, between 1 and 4 Market
Access specialists, one country based MSL per four
sales representatives, and then, in Europe, at the
international level, 2–3 marketing individuals and the
same for Medical Affairs.
The skills of the individuals in these roles, and how
they work together as a team will be vital, requiring
careful planning and investment. Start team building
early, use in house resources, or, if working with
an outsource partner seek to ensure a long-term
contract and dedicated, experienced team. Ensure
that performance evaluation and incentives are team
based and focused on the long term. Build in time and
space for sharing of learnings across countries and
across functions, especially if the market access and
launch process proceeds at different speeds between
countries. Consider moving some key individuals
between countries as the launch rolls out, so they can
take learnings with them and accumulate experience.
iqviabiotech.com | 17
 CONCLUSION
The Orphan Medicines environment today is very
different to that when the original legislation was
enacted. The overall pharmaceutical industry
environment, in terms of what types of innovative
medicines are launched and generate the most
value, has also transformed, with the rise of specialty
products leading value growth. Orphan Medicines once
stood outside the mainstream of the pharmaceutical
business. Now, the gap in nature
and market circumstance between these products
and the mainstream is often narrow and may narrow
still further.
The fundamental principles of Launch Excellence,
which IQVIA has documented in five Launch Excellence
white papers over the last decade, 32 therefore apply to
Orphan Medicines as much as they do to mainstream
innovative launch.
However, there are also areas of specific focus to
succeed and have an Excellent launch with an Orphan
Medicine: more complex market access challenges,
18 | Orphan Medicines Launch Excellence: Sustaining launch success as Orphan Medicines come of age
patient insight and patient access, and a highly patient
centric approach are necessities. Therefore, there are
requirements for a unique launch and go to market
model, addressing the challenges of forecasting,
patient insight development, payer and patient value
propositions, patient registries and medicine supply.
Lastly, Orphan Medicine companies are diverse, and
increasingly see smaller, often Biotech companies
commercialising their own innovations, but doing so
in an environment where they may compete alongside
mainstream big pharma. Smaller companies can
and do achieve Launch Excellence with their Orphan
Medicines, because they can leverage the advantages
of lower costs, infrastructural support, limited country
markets and customer intimacy. They must, however,
ensure they plan early, internationally, and with a
multi-functional team in place across the spectrum of
customer focused activity. Companies that succeed in
accomplishing Launch Excellence in the Orphan field
may well, in the future, be able to teach the marketeers
of mainstream innovative launches a thing or two.
REFERENCES

1. IQVIA: Launch Excellence series. https://www.iqvia.com/library/white-papers/launch-excellence-v

2. https://www.ema.europa.eu/en/human-regulatory/overview/orphan-designation-overview

3. Establishing a Reasonable Price for an Orphan Medicine - Mikel Berduda, Michael Drummond and
Adrian Towse, Office of Health Economics, University of York (July 2018)

4. Biotech origin, Parenteral administration, Require Patient Monitoring and Education, Treatment for a
chronic condition, Disease Treatment initiated by a specialist, Distribution requires special handling,
Expensive cost of treatment, Unique distribution

5. IQVIA analysis, MIDAS data Q4 MAT LCUSD 2009-2018 (Rx only)

6. https://www.ema.europa.eu/documents/report/human-medicines-highlights-2017_en.pdf EMA
Human Medicines summary

7. Advancing Health through Innovation: 2018 New Drug Therapy Approvals report https://www.fda.gov/
Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm629241.htm

8. IQVIA analysis 2019: FDA Novel Drug Approvals and EMA Human Medicines Highlights 2014-2018

9. IQVIA: Launch Excellence series. https://www.iqvia.com/library/white-papers/launch-excellence-v

10. IQVIA Institute: Orphan Medicines in the United States, Growth Trends in Rare Disease – 2018; https://
www.iqvia.com/institute/reports/orphan-drugs-in-the-united-states-growth-trends-in-rare-disease-
treatments#reportcharts

11. IQVIA internal analysis, also (separately) several studies cited in Breaking the Access Deadlock:
Eurordis, January 2018

12. In Vivo 2017: Orphan Medicine pricing and reimbursement: Challenges to patient access

13. Figure 8: IQVIA analysis, HTA Accelerator data 2012 – 2018, Company size determined by MIDAS
LCUSD sales data during respective year. Large = top-20 pharma companies, Medium = top20 - 100
companies, and small = other companies, universities and charities

14. Note: *Only Ph1/2 and above considered. Source: https://ojrd.biomedcentral.com/

articles/10.1186/1750-1172-6-71, IQVIA Experties, https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC5829132/pdf/40265_2018_Article_868.pdf

iqviabiotech.com | 19
 REFERENCES

15. IQVIA Institute, Orphan Medicines in the United States, Exclusivity, Pricing and Treated Populations,
December 2018

16. Breaking the Access Deadlock: EURORDIS, January 2018

17. https://www.genomicsengland.co.uk/iqvia-genomics-england-e360-platform/

18. IQVIA blog (2017); https://www.iqvia.com/blogs/2017/04/involving-families-in-rare-disease-clinical-

trials

19 European Commission – Factsheet, metabERN European Reference network; last accessed March
2019 https://ec.europa.eu/health/sites/health/files/ern/docs/metabern_factsheet_en.pdf.

20. IQVIA & ARM Foundation for Cell and Gene Medicine - “First of its kind” http://thearm.foundation/
category/economic-impact/

21. IQVIA analysis, Availability of 104 Orphan drugs approved versus non-Orphan new active
substances launched between 2005 – 2017. MIDAS sales used to define availability

22. IQVIA European Thought Leadership analysis (2017); HTA-Accelerator dataset, 2006-2016. (*
Positive = full access as per label; Restricted = access but with label restrictions; negative = no
access granted. ** In DE, Positive = “minor” or “major additional benefit” rating, Restricted = “non-
quantifiable additional benefit” rating, no negative ratings due to OD law mandating that drugs
with OD designation automatically receive an “additional benefit” rating

23. Roche, IQVIA, and Public Policy Projects, ‘Leaving No-One Behind: Improving Access for Rare
Diseases in the UK’, 2018

24. IQVIA European Thought Leadership & Consulting Services analyses; Pricing and market access
routes to access across the top-5 European markets (2019)

25. IQVIA European Thought Leadership Analysis (2019); HTA-Accelerator data 2012-2018; Company size
determined by MIDAS LCUSD sales data during respective year. Large = top-20 pharma companies,
Medium = top20 - 100 companies, and small = other companies, universities and charities

26. Advancing gene Therapies and Curative Health Care Through Value-Based Payment Reform , Health
Affairs, 2017 https://www.healthaffairs.org/do/10.1377/hblog20171027.83602/full/

27. IQVIA Analytics Centre of Excellence (ACOE) 2019; Case study: Physician Referral Networks

28. Overview on State of the Art on Rare Disease Activities in Europe: http://www.rd-action.eu/wp-
content/uploads/2018/09/Final-Overview-Report-State-of-the-Art-2018-version.pdf

20 | Orphan Medicines Launch Excellence: Sustaining launch success as Orphan Medicines come of age
29. IQVIA White Paper, 2019: Registries for Rare Diseases- A foundation for multi-arm, multi-company
trials- https://www.iqvia.com/library/white-papers/registries-for-rare-diseases

30. Orphanet; Rare Disease Registries in Europe (May 2018) https://www.orpha.net/orphacom/cahiers/

docs/GB/Registries.pdf

31. Driving Launch Success: less can be more with the right channel mix recipe- IQVIA White paper,
2018. https://www.iqvia.com/library/white-papers/driving-launch-success

32. Launch Excellence V: Surviving and thriving in an increasingly specialised world. https://www.iqvia.
com/library/white-papers/launch-excellence-v

iqviabiotech.com | 21
 CONTACT US
iqvia.com/contactus

Copyright © 2019 IQVIA. All rights reserved. 03.2019.NEMEA