Over 350 million people worldwide are suffering from rare diseases. Which is why it is necessary to understand the rare disease landscape to date. Drug development is challenging at the best of times, and made even harder within the realm of rare diseases. Overall, the largest number of drugs has targeted indications within the therapeutic areas of oncology and infectious disease (ID), with malaria being an area of high interest with both therapeutic and preventive interventions. View this slideshare to get the most accurate and timely intelligence about rare diseases drug development. In this detailed 20-page report, containing numerous comparative graphs, you will discover: - The top 25 Rare Diseases by total drugs in development to date - Current Rare Disease drug development landscape - Top 15 originators of drugs in development for Rare Diseases (includes non-rare disease drug counts and % of portfolio dedicated to Rare Diseases) - Therapeutic area distribution of rare diseases and drugs in development - The top 5 Rare Diseases by drug count per therapeutic area (TA) - Rare Infectious Diseases with 10 or more drugs in development - The top 15 originators developing drugs for Rare Infectious Diseases - Rare cancers with 10 or more drugs in development - The top 15 originators developing drugs for rare cancers - Non-ID, non-cancer Rare Diseases with 20 or more drugs in development - The top 15 originators developing drugs for non-ID, non-cancer Rare Diseases

1. A Bird’s-Eye View of the Rare
Disease Landscape

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The focus of this analysis is limited to indications
considered to be a rare disease as defined by the
FDA and EMA. Specifically, these are the conditions
that affect 200,000 people or less in the US (FDA) or
ones with a prevalence of 1 in 2,000 people, which
is the equivalent of fewer than 250,000 people in
the EU (EMA). As of October 2016, Pharmaprojects
captured a total of 9,626 drugs in development
for at least one of these rare diseases. Among
the 499 Pharmaprojects indications designated
as rare diseases, 494 have been addressed by the
pharma industry with focus areas made evident
by total number of drugs developed per indication,
both active (drugs still in preclinical or clinical
development, registered, approved or launched)
and inactive (drugs that have been suspended,
discontinued, withdrawn, or active development
cannot be confirmed in the public domain).
Overall, the largest number of drugs have targeted
indications within the therapeutic areas of Cancer
and Infectious Disease (ID). Among the top 25 rare
disease categories depicted in Figure 1, combatting
cancer does appear to be the pharma industry’s
priority as the first seven are all oncology indications.
Ovarian and pancreatic cancer have been targeted
the most, both historically and currently, with a total
of 880 and 851 drugs, respectively. Liver cancer is a
distant third with 539 total drugs, followed by renal,
acute myelogenous leukemia (AML), myeloma, and
stomach cancer. For most of these top cancers, the
number of inactive drugs outnumber those still in
active development, however, efforts are clearly still
ongoing.
Within ID, malaria has been an area of high interest
with both therapeutic and preventive interventions
in the top 25. Unfortunately, this is primarily due
to abandoned efforts against this mosquito-borne
disease; 70% of malaria treatments and 80% of
prophylaxis candidates are inactive. There are a
few rare infectious diseases where interest is far
from waning, specifically tetanus prophylaxis and
pertussis prophylaxis, both of which possess a higher
proportion of active drugs. (Figure 1)
A reflection on the rare disease landscape to date
Drug development is a challenging endeavor, which
can be further exacerbated within the realm of rare
diseases. Some additional issues encountered in this
area include limited precedent for drug development
within individual disorders, which typically have
poorly understood natural histories, and very small
populations affected by the disease. However, while
individual rare diseases may only affect a small
pool of patients, rare disease patients as a whole
are quite numerous at an estimated 350 million
people worldwide. Perhaps most troubling is the
fact that about half of these patients are children,
30% of whom will not live to see their fifth birthday
per Global Genes®, a rare disease patient advocacy
group. Various regulations and initiatives have been,
and continue to be, implemented to both facilitate
and incentivize rare disease R&D, and the pharma
industry appears to be responding accordingly.
Doro Shin
Thought Leadership Manager

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Figure 1. Top 25 Rare Diseases by Total Drugs in Development to Date
Source: Pharmaprojects, October 2016
*Active includes both pipeline (preclinical, Phase I-III, pre-registration) and approved (registered and launched) drugs
InactiveActive*
Cancer, ovarian
Cancer, pancreatic
Cancer, liver
Cancer, renal
Cancer, leukemia, acute myelogenous
Cancer, myeloma
Cancer, gastrointestinal, stomach
Infection, malaria
Cystic fibrosis
Amyotrophic lateral sclerosis
Cancer, esophageal
Infection, tuberculosis
Myelodysplastic syndrome
Cancer, lung, small cell
Infection, tetanus prophylaxis
Huntington’s disease
Cancer, leukemia, chronic myelogenous
Growth hormone deficiency
Spinal cord injury
Fibrosis, pulmonary, idiopathic
Graft-versus-host disease
Hypertension, pulmonary
Infection, malaria prophylaxis
Hemophilia A
Infection, pertussis prophylaxis
0 200 400 600 800
408 472
417 434
268 271
214 279
276 206
255 217
217 174
88 203
97 181
106 139
121 112
74 153
133 89
98 118
130 50
55 121
82 90
40 132
52 119
92 76
82 81
67 94
32 128
76 81
106 48
Drug count

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The current status of active drug development for rare diseases
Pharmaprojects last assessed the rare disease
landscape in a November 2013 white paper, which
found that 2,907 drugs were in active development
for at least one of 364 rare diseases1
. As of October
2016, a total of 4,549 drugs are now in development
for at least one of 447 rare diseases. This is an
increased drug count of 56% and 23% more rare
diseases after nearly three years, demonstrating
ongoing interest and seemingly increased
enthusiasm for research within these areas of high
unmet needs. As previously mentioned, a total of
494 rare indications have been targeted by pharma
to date, leaving 47 as orphaned indications with no
currently active drugs. These were generally much
smaller efforts that peaked at a high of 13 total
drugs previously in development for schistosomiasis
prophylaxis. Ongoing therapeutic research for
schistosomiasis remains, so the disease has not
been completely abandoned.
With regard to the breakdown by disease status,
or the highest phase of development a drug has
reached for a particular disease, preclinical and
early-to-mid stage clinical research continues to be
the most active. In addition to the large proportion
of early stage developments, a total of 1,387
launches have taken place. (Figure 2) Since drugs
in development for more than one rare disease
are counted for each individual indication, the
same drug can be counted both across and within
the same development phase. As such, this total
of 1,387 launches represents 950 unique drugs
that have been launched across 232 different rare
diseases. Among these marketed products, ID is
in the lead, with the largest number of launches,
followed by Cancer.
Figure 2. Current Rare Disease Drug Development Landscape*
Source: Pharmaprojects, October 2016
*Drugs in development for >1 rare disease are represented at multiple development phases
1 Stephens J, Blazynski C (2013) Rare Disease Landscape: Will the Blockbuster Model be Replaced? Available from: https://pharmaintelligence.informa.
com/resources/product-content/will-the-blockbuster-model-be-replaced
3000
2500
2000
1500
1000
500
0
#drugsindevelopment
Preclinical
Phase
I
Phase
II
Phase
III
Pre-registration
Registered
Launched
2564
1334
1558 1387
470
74 36

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Leaders of the rare disease pack
Figure 3 provides a view of the frontrunners within
rare disease R&D, limiting drug counts to those
originally discovered/synthesized by the company
or group. Development is led by the trio of Sanofi,
GlaxoSmithKline (GSK), and Novartis who all
originated over 90 unique drugs each. While Sanofi
does top the list of key originators, they only have a
small lead ahead of GSK and Novartis. After the top
three, drug counts start dropping markedly. Nearly
all originators are within the Top 20 Pharma peer
set, based on the company’s revenue, with Eisai
and the Medicines for Malaria Venture (MMV) as the
exceptions. The Medicines for Malaria Venture is truly
an exception as it is the only non-profit foundation
within the Top 15 rare disease drug originators,
beating numerous pharma and biotech companies,
in addition to the fact that the foundation focuses
on a single rare disease.
Considering the vast majority of originators are also
Big Pharma companies, the higher number of rare
disease drugs could be a reflection of their large
portfolios rather than their commitment toward
combatting rare diseases. As such, Figure 3 also
includes the number of non-rare disease drugs to
indicate the proportion of their portfolio focused
on rare diseases. Besides MMV, whose sole focus is
malaria, the non-Top 20 company Eisai becomes
the leader with the largest percentage of rare
disease drugs (43%), followed by Amgen (38%).
Interestingly, Sanofi, GSK, and Novartis are still key
players with a three-way tie as rare disease drugs
comprise 31% of each of their originated drug
portfolios.
Figure 3. Top 15 Originators of Drugs in Development for Rare Diseases (Includes Non-Rare Disease Drug
Counts and % of Portfolio Dedicated to Rare Diseases)
Source: Pharmaprojects, October 2016
*Count limited to number of originated drugs and does not include any licensed assets
Non-rare diseaseRare disease
Sanofi
GlaxoSmithKline
Novartis
Pfizer
Roche
Johnson & Johnson
Bristol-Myers Squibb
Takeda
Amgen
AstraZeneca
Eisai
Bayer
Merck & Co.
Medicines for Malaria Venture
Eli Lilly
0 100 200 300 400
# drugs *
98 223
96 211
93 205
74 291
58 161
38 178
34 137
34 131
32 53
32 149
30 40
28 124
27 213
26 100%
25 106
31%
31%
31%
20%
26%
18%
20%
21%
38%
18%
43%
18%
11%
19%

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Therapeutic focus remains consistent
Figure 4 provides the development landscape across
the Pharmaprojects therapeutic areas (TAs) by the
number of drugs as well as the number of diseases,
consistent with the 2013 analysis1
. Cancer and ID
continue to be the industry’s focus within active
drug development and both areas are the most
prolific in terms of drug count. This is true for both
the total number of ‘drugs’ per TA, which includes a
count for each indication when drugs are developed
for more than one rare disease within the TA, and
when drugs targeting multiple rare diseases within
the TA are only counted once (the number of unique
drugs per TA). The vast majority of anticancer drugs
pursue multiple rare oncology indications, which is
evident by the large difference between total and
unique number of drugs. In general, most TAs do
have drugs that pursue multiple indications, but
not to the same dramatic extent as anticancer
therapies.
ID has the largest number of rare diseases
with drugs in development, followed closely by
Alimentary/Metabolic, however, both TAs also have
the most designated rare diseases (represented
by the total height of the columns in Figure 4).
Currently, drug development is active in 87% of
rare infectious diseases and 92% of rare alimentary
and metabolic conditions. Blood & Clotting,
Genitourinary, and Hormonal all have R&D activity
in each of their designated rare diseases, while
the largest gap is observed in Dermatological and
Cardiovascular, where 24% and 21% of their rare
diseases, respectively, remain unaddressed by active
drugs.
Figure 4. Therapeutic Area Distribution of Rare Diseases and Drugs in Development
Source: Pharmaprojects, October 2016
* Drugs in development for more than one rare disease within the therapeutic area are counted for each indication
§ Count of each unique drug within the therapeutic area (i.e. drugs in development for more than one rare disease within the
therapeutic area are only counted once).
120
100
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60
40
20
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3500
3000
2500
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1000
500
0
#rarediseases
InfectiousDisease
Alim
entary/M
etabolicNeurological
Cancer
M
usculoskeletal
Blood
and
Clotting
Im
m
unological
Sensory
Cardiovascular
Derm
atologicalRespiratoryHorm
onal
Genitourinary
#drugsforrarediseases
# diseases with active drugs # diseases with no active drugs # total drugs per TA* # unique drugs per TA§

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Although there appears to be some diversity given
the number of diseases with active drugs, the top
five rare diseases per TA by drug count indicate
otherwise. These are provided within Table 1, which
depicts the skewed distribution of R&D activity as
the sum drug count for the top five indications
within a TA tends to comprise the majority of the
total drug count. The exceptions are Alimentary/
Metabolic (106/386; 27%), ID (471/1404; 34%), and
Neurological (251/599; 42%), which are also the
three largest TAs with respect to the number of rare
diseases. Cancer is right on the edge and the sum of
active drugs for the top five rare cancers represent
50% of the efforts within this area (1624/3235).
The largest rare indications by number of drugs are
the top five cancers of pancreatic, ovarian, acute
myelogenous leukemia, liver, and myeloma. Not
only do these cancers lead the rare disease R&D
overall, but the drug counts for a single cancer
outnumber the total drug counts for some of the
TAs. For instance, myeloma’s 255 drugs outnumber
the total efforts for Sensory, Cardiovascular,
Dermatological, Hormonal, and Genitourinary
combined. The 417 drugs for the largest rare cancer,
pancreatic, outpace all non-cancer TAs except for
ID, Neurological, and Blood and Clotting. Outside
of cancer, myelodysplastic syndrome, which can
be triggered by cancer treatments, has the largest
number of drugs, followed by tetanus prophylaxis.
(Table 1)
Table 1. Top 5 Rare Disease by Drug Count per Therapeutic Area (TA)
Therapeutic Area
(Total Drugs per TA)
Disease # drugs % of total drugs per TA
Alimentary/Metabolic
(n = 386)
Behcet's disease 29 8%
Sjogren's syndrome 24 6%
Cirrhosis, primary biliary 19 5%
Gaucher's disease 18 5%
Fabry's disease 16 4%
Blood and Clotting
(n = 532)
Myelodysplastic syndrome 133 25%
Hemophilia A 76 14%
Hemophilia B 42 8%
Thrombocytopenic purpura, idiopathic 37 7%
Anaemia, sickle cell 35 7%
Cancer
(n = 3235)
Cancer, pancreatic 417 13%
Cancer, ovarian 408 13%
Cancer, leukemia, acute myelogenous 276 9%
Cancer, liver 268 8%
Cancer, myeloma 255 8%
Cardiovascular
(n = 133)
Hypertension, pulmonary 67 50%
Angioedema, hereditary 17 13%
Pre-eclampsia 8 6%
Buerger's syndrome 8 6%
Homocystinuria 6 5%
Dermatological
(n = 123)
Scleroderma 35 28%
Epidermolysis bullosa 20 16%
Pemphigus 10 8%
Mastocytosis 10 8%
Ichthyosis 9 7%

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Genitourinary
(n = 63)
Nephritis, lupus 20 32%
Sex-chromosome abnormality, Turner's syndrome 9 14%
Precocious puberty 9 14%
Glomerulonephritis 6 10%
Berger's disease 6 10%
Hormonal
(n = 122)
Growth hormone deficiency 40 33%
Acromegaly 27 22%
Cushing's disease 19 16%
Secondary hyperparathyroidism 15 12%
Adrenal insufficiency, primary, congenital 6 5%
Immunological
(n = 377)
Graft-versus-host disease 82 22%
Arthritis, juvenile 80 21%
Scleroderma 35 9%
Wegener's granulomatosis 28 7%
Microscopic polyangiitis 26 7%
Infectious Disease
(n = 1404)
Infection, tetanus prophylaxis 130 9%
Infection, pertussis prophylaxis 106 8%
Infection, malaria 88 6%
Infection, tuberculosis 74 5%
Infection, Haemophilus influenzae prophylaxis 73 5%
Musculoskeletal
(n = 342)
Arthritis, juvenile 80 23%
Dystrophy, Duchenne's muscular 65 19%
Myasthenia gravis 21 6%
Muscular atrophy, spinal 18 5%
Dwarfism 16 5%
Neurological
(n = 599)
Amyotrophic lateral sclerosis 106 18%
Huntington's disease 55 9%
Spinal cord injury 52 9%
Ataxia, Friedreich's 19 3%
Narcolepsy 19 3%
Respiratory
(n = 300)
Cystic fibrosis 97 32%
Fibrosis, pulmonary, idiopathic 92 31%
Bronchiectasis 21 7%
Emphysema, alpha-1 antitrypsin deficiency 17 6%
Acute lung injury 16 5%
Sensory
(n = 187)
Uveitis 55 29%
Retinitis pigmentosa 31 17%
Sjogren's syndrome 24 13%
Neuromyelitis optica 15 8%
Blepharospasm 8 4%
Source: Pharmaprojects, October 2016

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Infectious Disease activity
The large number of designated rare diseases for
ID in Figure 4 can partially be attributed to the
fact that many infections are combatted through
prophylactic and therapeutic means, which
are distinct indications within Pharmaprojects.
However, ID remains one of the biggest TAs by
disease number with a total of 69 unique rare
infectious diseases. Among the 101 Pharmaprojects
indications designated as rare diseases, 39 are
specific to prophylaxis while 62 treat rare infectious
diseases. Despite this, the proportion of activity is
skewed toward prevention, which comprises 24 of
the 33 rare ID indications with 10 active drugs or
more. (Figure 5) Vaccines are the primary strategy
pursued for these preventative interventions, and it’s
not surprising to see large efforts within prophylaxis
since the creation of vaccines is considered to
be one of the most important public health
achievements of the 20th century.
The leading rare infectious diseases by total
number of active drugs are tetanus prophylaxis,
pertussis prophylaxis, malaria, tuberculosis, and
Haemophilus influenzae (Hib) prophylaxis. However,
the drug counts for all the prophylaxis indications
are driven by the number of approved products;
there are 105 launched products for tetanus, 77 for
pertussis, and 49 for Hib prophylaxis. In contrast,
the development of malaria and tuberculosis
therapeutics is dominated by preclinical compounds,
and these indications only have 16 and 10 launched
therapeutics, respectively. Both tuberculosis
prophylaxis and malaria prophylaxis also appear
at 9th and 12th place, suggesting that they are a
top priority for the pharma industry as they seek
to eradicate these rare infectious diseases with
multiple strategies.
The headline-grabbing outbreaks of the Ebola,
Zika, and dengue viruses have certainly spurred
the industry into action, and all three have at
least 20 active drugs in development or more for
both prophylaxis and treatment. Out of the three
vector-borne viruses, only a single product has been
launched, which is Sanofi’s dengue fever vaccine
Dengvaxia. R&D activity across the three viruses
is primarily preclinical; specifically, over 80% of
therapeutics for Ebola and dengue and more than
90% of Zika prophylaxis and treatment are reported
to be in preclinical development. (Figure 5)

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Figure 5. Rare Infectious Diseases with 10 or More Drugs in Development*
Source: Pharmaprojects, October 2016
*Infectious Disease indications without the term “prophylaxis” represent therapeutic interventions for the infection
Preclinical Phase I Phase II Phase III Pre-registration Registered Launched
Infection, tetanus prophylaxis
Infection, pertussis prophylaxis
Infection, malaria
Infection, tuberculosis
Infection, Haemophilus influenzae prophylaxis
Infection, meningococcal prophylaxis
Infection, Ebola virus
Infection, polio prophylaxis
Infection, tuberculosis prophylaxis
Infection, Clostridium difficile
Infection, dengue virus
Infection, malaria prophylaxis
Infection, rabies prophylaxis
Infection, leishmaniasis
Infection, Ebola virus prophylaxis
Infection, Zika virus prophylaxis
Infection, typhoid prophylaxis
Infection, Zika virus
Infection, rubella prophylaxis
Infection, Aspergillus
Infection, Haemophilus influenzae
Infection, dengue virus prophylaxis
Infection, Clostridium difficile prophylaxis
Infection, anthrax prophylaxis
Infection, onychomycosis
Infection, trypanosomiasis, American
Infection, Japanese encephalitis virus prophylaxis
Infection, mumps prophylaxis
Infection, Kawasaki disease
Infection, helminth, unspecified
Infection, anthrax
Infection, Chikungunya virus prophylaxis
Infection, smallpox virus prophylaxis
0 20 40 60 80 100 120 140
# drugs per indication

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Figure 6. Top 15 Originators Developing Drugs for Rare Infectious Diseases
An overview of key ID players is provided in Figure 6,
which includes the top 15 originators based on the
total number of unique drugs active for at least one
rare infectious disease. Sanofi leads with a total of
58 drugs, largely driven by the number of launched
vaccines (41). GlaxoSmithKline and Novartis follow,
with launched vaccines as approximately half of
their portfolio. Other large pharma companies within
the top 15 include Johnson & Johnson at sixth place
and Pfizer at 14th, but the remainder of the roster is
somewhat atypical.
Fourth place goes to the aforementioned Medicines
for Malaria Venture (MMV), a non-profit foundation
whose stated mission is to discover, develop, and
deliver affordable antimalarial drugs by fostering
public-private partnerships. Another foundation with
a similar mission, but for a different disease, is the
TB alliance, and they are joined at the top by DNDi.
The collaborative non-profit drug R&D organization
DNDi, which stands for Drugs for Neglected Diseases
initiative, develops new treatments for neglected
diseases. Unlike the large pharma companies at
the top of the list, DNDi is the only one of the three
to have any launched products, one for African
trypanosomiasis and one for malaria. The remainder
of their activity primarily lies in preclinical.
In addition to the non-profit organizations, rare
infectious disease R&D is driven by companies from
the emerging markets of India and China as top
originators. A closer look at their portfolios finds that
nearly all their efforts leverage vaccines to prevent
some well-known infections, such as meningitis,
pertussis, rubella, and tetanus. However, these
companies also target more exotic diseases such
as leptospirosis and hemorrhagic fever, as well as
the vector borne diseases of Chikungunya and Zika.
(Figure 6)
Source: Pharmaprojects, October 2016
Sanofi
GlaxoSmithKline
Novartis
Medicines for Malaria Venture
China National Pharmaceutical
Johnson & Johnson
Serum Institute of India
TB Alliance
Bharat Biotech
Microgen
Beijing Tiantan Biological
DNDi
Zydus Cadila
Pfizer
Chongqing Zhifei Biological
0 10 20 30 40 50 60 70
# unique drugs

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Source: Pharmaprojects, October 2016
Spotlight on rare cancers
A total of 35 cancers have 10 active drugs or
more, as depicted in Figure 7. The most active
development is pancreatic and ovarian cancer, with
417 and 408 drugs, respectively. While the top rare
infectious diseases were generally weighted toward
launched drugs, the rare cancer landscape paints
a different story and efforts are primarily still in
preclinical and early stage development. Launched
options do exist for all the top rare cancers, just
at a much smaller proportion in comparison to
ID. Cancers with the largest number of launched
drugs are ovarian, renal, chronic myelogenous
leukemia, Kaposi’s sarcoma, and hairy cell leukemia.
Overall, R&D activity is concentrated in the top 5
as previously stated, but there is also a fair level of
effort for stomach and renal cancer. Counts of active
drugs do start dropping markedly from esophageal
cancer onward.
Figure 7. Rare Cancers with 10 or more Drugs in Development
Cancer, pancreatic
Cancer, ovarian
Cancer, leukemia, acute myelogenous
Cancer, liver
Cancer, myeloma
Cancer, gastrointestinal, stomach
Cancer, renal
Cancer, esophageal
Cancer, lung, small cell
Cancer, fallopian tube
Cancer, leukemia, chronic myelogenous
Cancer, biliary
Cancer, lymphoma, mantle cell
Cancer, mesothelioma
Cancer, lymphoma, Hodgkin’s
Cancer, sarcoma, soft tissue
Cancer, neuroblastoma
Cancer, gastrointestinal, stromal
Cancer, lymphoma, T-cell, cutaneous
Cancer, sarcoma, Kaposi’s
Cancer, leukemia, hairy cell
Cancer, leukemia, chronic myelomonocytic
Cancer, sarcoma, osteo
Cancer, lymphoma, T-cell, peripheral
Cancer, nasopharyngeal
Cancer, sarcoma, Ewing’s
Waldenstrom’shypergammaglobulinaemia
Cancer, bone
Cancer, lymphoma, B-cell, marginal zone
Cancer, carcinoid
Cancer, urethral
Cancer, sarcoma, lipo
Cancer, testicular
Cancer, sarcoma, rhabdomyo
Cancer, Merkel cell carcinoma
0 20 40 60 80 100 120 140 160 180
# drugs per indication
Preclinical
Phase I
Phase II
Phase III
Pre-registration
Registered
Launched

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Among the top 15 originators within the anticancer
space depicted in Figure 8, Novartis is the most
active, both for the total number of unique drugs,
as well as the number of pipeline candidates in
development for at least one rare cancer. Pfizer
and Roche tie for second place and the companies
also possess the same number of unique launched
drugs. However, across these top three originators,
only a subset of their launched drugs have been
approved for rare cancers. Most of their launched
drugs have been launched for non-rare cancers,
such as breast cancer. All three are pursuing a
wide range of indications, including the ubiquitous
pancreatic and ovarian cancers. Novartis has active
drugs across 29 rare cancers and again, Pfizer and
Roche tie with 23.
The burgeoning field of immuno-oncology (IO)
continues to be an area of high interest and nine
originators within this cohort are evaluating at least
two immunotherapies for rare cancers. Amgen leads
with five immuno-oncology drugs, which includes
Imlygic, the first approved oncolytic viral therapy in
the US that was launched for melanoma last year.
Imlygic is under evaluation for a handful of non-rare
oncology indications, and is currently in a Phase I
trial for liver cancer. None of Amgen’s IO drugs have
progressed beyond Phase I for rare cancers, and
the largest efforts are observed with solitomab, an
epithelial cell adhesion molecule inhibitor under
evaluation in five different rare indications.
All the top originators also lead in their IO efforts.
Novartis and Roche tie with four IO drugs each,
while Pfizer has three. Roche’s primary effort has
been with Tecentriq, which was recently approved
for metastatic non-small cell lung cancer. This
PD-L1 antagonist is still being studied in nine rare
indications spanning from preclinical to Phase
III development, with small cell lung, renal,
and urethral cancer as the forerunners. Another
launched immunotherapy, GlycArt, is under
evaluation for rare cancers. This CD20 antagonist
has been approved for chronic lymphocytic leukemia
(CLL) and registered for non-Hodgkin’s lymphoma
(NHL). As of October 2016, GlycArt remains under
clinical development for additional lymphoma types:
marginal zone B-cell (Phase III) and mantle cell
(Phase II). Roche’s remaining two immunotherapies,
emactuzamab and ERY-974, are unapproved
compounds that have not yet progressed beyond
Phase II development.
Novartis also has four immuno-oncology drugs,
including three chimeric antigen receptor T-cell
(CAR-T) therapies that have been developed based
on the in-licensed technology from the University
of Pennsylvania. Part of the deal included CTL019,
which targets CD19 expressed on cancer cells and is
in Phase II for Hodgkin’s Lymphoma, but is mostly
evaluated in non-rare cancers. Another is directed
against mesothelin and is in Phase I trials to treat
mesothelioma, pancreatic and ovarian cancer. A
more recent candidate is an anti-BCMA CAR-T cell
therapy with tandem TCR and 4-1BB costimulatory
domains for the treatment of myeloma. This drug is
also in a Phase I trial that is expected to complete in
2017. Despite the numerous candidates and clinical
activity, in August 2016 the company announced
plans to disband its cell and gene therapy unit.
Although Novartis has reassured the public that they
remain committed to the CAR-T space, it remains
to be seen whether this commitment will be limited
to the impending FDA filing of CTL019 for acute
lymphoblastic leukemia (ALL) in early 2017.

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Figure 8. Top 15 Originators Developing Drugs for Rare Cancers
Source: Pharmaprojects, October 2016
Non-ImmunotherapyImmunotherapy
Novartis
Pfizer
Roche
Amgen
AstraZeneca
Eli Lilly
Bristol-Myers Squibb
GlaxoSmithKline
Eisai
Takeda
Celgene
Bayer
OncoTherapy Science
MabVax Therapeutics
Boehringer Ingelheim
0 10 20 30 40
# unique drugs
4 34
3 25
4 24
5 15
2 17
18
3 13
14
14
13
2 10
12
11
2 9
92

16. 16 / January 2017 © Informa UK Ltd 2016 (Unauthorized photocopying prohibited.)
What’s happening elsewhere?
Although ID and Cancer are the largest TAs for
rare disease drug development, activity is far from
limited outside these arenas. A total of 76 non-ID,
non-Cancer rare diseases have 10 or more active
drugs, and 31 have 20 or more as depicted in Figure
9. Among these diseases with 20 or more active
drugs, Blood & Clotting and Immunological are the
most represented TAs based on number of diseases
and the total number of drugs. Both appeared to
be less active in Figure 4, but drug development in
these TAs are more concentrated among a smaller
group of diseases.
Myelodysplastic syndrome is the largest non-ID,
non-Cancer rare disease with a total of 133 active
drugs. However, radiation and chemotherapy are
among the known triggers of development for this
group of bone marrow disorders, and the Blood &
Clotting indication could be considered tangentially
related to cancer. Amyotrophic lateral sclerosis
(ALS) follows with 106 active drugs, which includes
a total of three launched and one registered drugs.
In the 2013 analysis, only a single drug had been
launched for ALS1
. Since then, the rare disease was
spurred into the spotlight following the viral Ice
Bucket Challenge that raised USD 115 million during
an 8-week period in 2014, USD 77 million of which
was dedicated to research2
. The bulk of ALS research
remains outside of clinical trials, with 66% of active
drugs still in preclinical development.
Two Respiratory rare diseases fall at third and fourth
place: cystic fibrosis and idiopathic pulmonary
fibrosis (IPF) with 97 and 92 drugs, respectively.
Following are the two Immunological indications
graft-versus-host disease (GVHD) and juvenile
arthritis. Most indications in Figure 9 have a
somewhat limited number of launched drugs,
especially in comparison to the top ID diseases, and
a large amount of preclinical activity. Development
stages beyond preclinical comprise the largest
proportion of drugs for only six non-ID, non-
cancer rare diseases. For hemophilia A, hemophilia
B, growth hormone deficiency and idiopathic
thrombocytopenic purpura, approximately half their
drugs are launched, while MDS and myelofibrosis
has the most activity in Phase II. There is also a
single rare disease, acromegaly, with the same
number of preclinical and launched drugs.
2 http://www.alsa.org/fight-als/ibc-progress.html [Accessed December 2016]

17. January 2017 / 17© Informa UK Ltd 2016 (Unauthorized photocopying prohibited.)
Figure 9. Non-ID, Non-Cancer Rare Diseases with 20 or more Drugs in Development
Source: Pharmaprojects, October 2016
Preclinical Phase I Phase II Phase III Pre-registration Registered Launched
Myelodysplastic syndrome
Amyotrophic lateral sclerosis
Cystic fibrosis
Fibrosis, pulmonary, idiopathic
Graft-versus-host disease
Arthritis, juvenile
Hemophilia A
Hypertension, pulmonary
Dystrophy, Duchenne’s muscular
Uveitis
Huntington’s disease
Spinal cord injury
Hemophilia B
Growth hormone deficiency
Thrombocytopenic purpura, idiopathic
Anaemia, sickle cell
Scleroderma
Retinitis pigmentosa
Behcet’s disease
Myelofibrosis
Wegener’s granulomatosis
Acromegaly
Microscopic polyangiitis
Thalassaemia
Sjogren’s syndrome
Myasthenia gravis
Bronchiectasis
Hemophilia, unspecified
Epidermolysis bullosa
Paroxysmal nocturnal haemoglobinuria
Nephritis, lupus
0 50 100 150
# drugs

18. 18 / January 2017 © Informa UK Ltd 2016 (Unauthorized photocopying prohibited.)
The top 15 originators for non-ID, non-Cancer drugs
are listed in Figure 10, which totals 17 companies
due to a three-way tie for 15th place. Novartis takes
the top spot again, followed by GSK, Pfizer, Sanofi,
and Roche. Beyond these five, there are a number
of originators who also appeared in the top rankings
for overall rare diseases R&D or the large realms of
ID and Cancer. However, new, and some smaller,
companies do enter the top rankings, namely CSL,
Baxter, Ionis Pharmaceuticals, Mitsubishi Tanabe,
Boehringer Ingelheim, and Sangamo BioSciences. All
these companies also have some activity within rare
infectious diseases and/or cancers, except Sangamo
whose rare disease developments are primarily
within Alimentary/Metabolic and Blood & Clotting.
Figure 10. Top 15 Originators Developing Drugs for Non-ID, Non-Cancer Rare Diseases
Source: Pharmaprojects, October 2016
Novartis
GlaxoSmithKline
Pfizer
Sanofi
Roche
CSL
Baxter International
Bristol-Myers Squibb
Amgen
Johnson & Johnson
Takeda
Bayer
Ionis Pharmaceuticals
AstraZeneca
Mitsubishi Tanabe Pharma
Boehringer Ingelheim
Sangamo BioSciences
0 10 20 30 40 50
# unique drugs

19. January 2017 / 19© Informa UK Ltd 2016 (Unauthorized photocopying prohibited.)
Conclusion
Despite the additional challenges of developing
drugs for rare diseases, it does not appear that
this landscape will fade anytime soon. Sanofi,
GSK, and Novartis lead the way with the largest
number of drugs, as well as Eisai and Amgen who
have dedicated a large percentage of their smaller
portfolios to rare diseases. The pursuit of potentially
life transforming treatments and preventative
measures to avoid certain diseases continues, with a
strong focus from the industry on ID and Cancer.

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