1. Ultra-orphan drugs: what is the long term
strategy to support ultra-orphan drugs &
how commercially viable are these drugs to
stakeholders
Presenter: Christian Girard, MiM
Chief Editor, Orphan Drugs Industry Insider
Founder & CEO, ABCrowdFunding Advisors

2.  Orphan disease prevalence: < 1/2.000
 Ultra-rare disease
prevalence: < 1/50.000
Picture: Alexion Pharmaceuticals

3.  Atypical Hemolytic Uremic Syndrome
(aHUS)
 N-acetylglutamate synthase deficiency
(NAGS deficiency)
 Hutchinson-Gilford progeria syndrome
(Progeria)
 Paroxysmal Nocturnal Hemoglobinuria
(PNH)
 Ribose-5-phosphate isomerase deficiency
(RPI deficiency)
 & many others…
 http://www.orpha.net/orphacom/cahier
s/docs/GB/Prevalence_of_rare_diseases
_by_decreasing_prevalence_or_cases.pd
f
 1-9/1.000.000 prevalence
 <1/1.000.000 prevalence
 1/8.000.000 prevalence
 1-9/1.000.000 prevalence
 1 case identified (1999)

4.  Atypical Hemolytic Uremic
Syndrome (aHUS)
 N-acetylglutamate synthase
deficiency (NAGS deficiency)
 Hutchinson-Gilford progeria
syndrome (Progeria)
 Paroxysmal Nocturnal
Hemoglobinuria (PNH)
 Ribose-5-phosphate
isomerase deficiency (RPI
deficiency)
 Soliris (eculizumab)
 Carbaglu (carglumic acid)
 Pravastatin / zoledronic acid
(not approved yet)
 Soliris (eculizumab)
 Not to our knowledge

5.  Carbaglu
 Glybera
 Soliris
 Orfadin
 Vimizim
 Juxtapid
 Cinryze
 Procysbi
 Up to 2.000k$
 Up to 1.600k$
 Up to 410k$
 Up to 400k$
 Up to 380k$
 Up to 380k$
 Up to 300k$
 Up to 250k$

6. PATIENTS $50 000 $100 000 $250 000 $500 000 $1 000 000
US 6 000 $300 000 000 $600 000 000 $1 500 000 000 $3 000 000 000 $6 000 000 000
EU 10 000 $500 000 000 $1 000 000 000 $2 500 000 000 $5 000 000 000 $10 000 000 000
US+EU 16 000 $800 000 000 $1 600 000 000 $4 000 000 000 $8 000 000 000 $16 000 000 000
Assumptions: 100% patients treated; disease prevalence = 1/50.000
POTENTIAL SALES (INCREASING PRICING VALUE)

7. 2014 SALES
Soliris $2 146 000 000
Cinryze $503 000 000
Procysbi $70 000 000
Vimizim $37 000 000

8.  Small molecules
 Biologics
 Gene therapies
 Ultra-rare drugs do not necessarily imply
advanced technology. Some are « simply »
repurposed small molecules

9.  Global cost of orphan drugs under scrutiny:
120B$ (ever increasing) – more than 10% of the
overall pharmaceutical market in 2014
 Ultra-rare drugs = high pricing (in investors’
opinion at least)
 Trend: increasing number of ultra-rare drugs
 Ultra-rare drugs efficacy?
 Room for negotiation with payors: very low
prevalence – patients registries – staged payment
terms
As a result, stellar pricing belongs to the past

10.  7.000+ orphan diseases identified
 ca. 500 drugs approved
 ca. 6.500 diseases without dedicated
treatment
 About 50% of them are ultra-rare disorders
 Orphan regulations incentives (7 to 10 year
market exclusivity starting at approval)
 Clinical trials cost lower (very few patients in
trials due to very low prevalence)
 Small-sized sales forces
 Historically, premium pricing (will this last?)
 Little or no competition… blue ocean strategy

11.  National plans or strategies for rare diseases
 EUROPLAN
 Budgets for ultra-rare diseases, but drops in
the ocean
 National & international patients
organizations much more active and
motivated
 Patients association offer support (initial
financing and in clinical trials)

12.  Leading orphan drugs players’ products &
R&D portfolio include ultra-rare drugs and
candidates
 Genzyme (Sanofi group)
 Shire
 Alexion Pharmaceuticals
 BioMarin Pharmaceutical
 Ultragenyx Pharmaceutical
 SOBI

13. Alexion
Pharmaceuticals:
37B$
BioMarin
Pharmaceutical:
22B$
Ultragenyx
Pharmaceutical:
3.7B$
Raptor
Pharmaceuticals:
1B$
Aegerion
Pharmaceuticals:
0.5B$

14. Alexion /
Synageva: 8.4B$
Horizon Pharma
/ Hyperion:
1.1B$
AbbVie /
Pharmacyclics:
21B$
Sanofi /
Genzyme: 20B$
Shire / NPS
Pharma: 5.2B$
Alexion /
Enobia: 1.1B$

17.  Any orphan drugs regulatory incentives in the
country (region)?
 If not, opt for development where these
incentives exist (US, EU, JP, AU, KR…)
 Ultra-rare diseases markets are not local:
they are global
 Out-licensing is an option

18.  Ultra-low prevalence justified (in industry’s
and investors’ view) high pricing for ultra-
rare drugs
 Non-ultra-rare drugs price tags can also be
stellar (eg. Vertex’ Kalydeco for Cystic
Fibrosis- 294k$)
 PTC Therapeutics’ Translarna (for Duchenne
Muscular Dystrophy – not an ultra-rare
disease) pricing questioned by payors
 Ultra-rare and «only» orphan drugs face the
same issues: can the payor (ie. the citizens)
accept to pay and how long?

19. Please contact Christian Girard at:
christian@orphandrugsindustry.com
Thank you.