Recent Orphan Drug companies

Experience with CUP, in Europe

François HouÿezDirector of Health Policy

6th ECRD, 23-25 May 2012, Brussels

Regulation EC 726/2004 Title V, article 83.2

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with a chronically or seriously debilitating disease

or whose disease is considered to be life-threatening

and who cannot be treated satisfactorily by an authorised medicinal product

Running a Compassionate Use Programme (CUP) consists in making a medicinal

product available for compassionate reasons to a group of patients:

F. Houÿez 25/05/2012

History

� US: Aids activists urged FDA to accelerate regulatory process– March on Wall Street (24 March 1987)

– FDA adopted the compassionate use scheme

� France 1988– French patients’ advocates negotiated early access with

health authorities

– 1991: ATU in Code de la Santé Publique

� Denmark: 1995

� Germany: 2005

� Italy: 2006

� Spain: 2009

F. Houÿez 25/05/2012 3

� A clinical trial nor an experiment:

– intention is to treat

� A substitute to product development:

– does not replace CT, should not even start if no CT

� A financial help programme nor a humanitarian

programme

� A way to place a product on the market prior to the

marketing authorisation

� A “favour” or a “gift” to clinicians who achieve their

objectives in recruiting for clinical trials

Compassionate use is not

F. Houÿez 25/05/2012 4

1st trimester 1995 – 3rd trimester 1998

Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q31995 1996 1997 1998

0

100

200

300

400

500

600

700

0

10000

20000

30000

40000

50000# hospitalisations

ATU IP IDV, RTV, SQV

ATU NRTI

Results as salvage

ATU 3TC

ATU d4T

MA

2Q96 to 2Q97: - 56%

A success story: hospitalisation rates for

1000 AIDS patients, France 1995-1998

F. Houÿez 25/05/2012 5

Some national schemes better than others

Afssaps annual report 2009

Afssaps annual report 2009

72% OD that were subsequently authorised

benefited from an ATU

72% OD that were subsequently authorised

benefited from an ATU

in average 34 months prior authorisation

F. Houÿez 25/05/2012 6

Equity guaranteed

RECENT ORPHAN DRUG COMPANIES

EXPERIENCE WITH CUP, IN EUROPE

Eurordis Survey with industry

F. Houÿez 25/05/2012 7

Methods (1)

� EURORDIS invitation letter sent in coordination with

EBE/EuropaBio

� Written questionnaire to person in charge of CUP in

64 companies• that obtained a MA for a designated OD within the last 3 years

(CUP in progress or closed)

• And/or are EBE/EuropaBio members or ERTC members

� Target: to obtain information on 15-20 products

� Survey period:

– November 2010 – January 2011

F. Houÿez 25/05/2012 8

Responses from 17 companies on 19 products

Company Product Indication CUP in Europe?

Eusa Pharma Inolimomab Graft versus host disease yes

Genzyme Mozobil® Treatment to mobilise progenitor cells prior to stem cell transplantation yes

AstraZeneca Vandetanib Medullary thyroid carcinoma Yes

Merck Serono Kuvan®Hyperphenylalaninaemia (HPA) in adult and paediatric patients of 4 years +

with (PKU)yes

Orphan Europe Carglumic acidNAGS deficiency, isovaleric acidaemia, methylmalonic acidaemia, propionic

acidaemiayes

Pharma Mar Yondelis® Soft Tissue Sarcoma yes

Shire Pharmaceuticals velaglucerase alpha (Vpriv) Gaucher type 1 Yes

Johnson&Johnson Decitabine MDS Yes

UCB Xyrem® Treatment of narcolepsy Yes

Swedish Orphan BioVitrum Kiobrina Prevention of growth restriction in preterm infants No

Chiesi Pharmaceutici

human corneal epithelium

containing stem cells Corneal lesions, with associated corneal (limbal) stem cell deficiency, due to

ocular burnsNo

Nymusa® Primary apnoea of premature newborns No

NovimmuneNI-0801 haemophagocytic lymphohistiocytosis No

NI-0501 haemophagocytic lymphohistiocytosis No

Talecris Biother. Gmbh Alpha-1-proteinase inhibitor Congenital alpha-1 antitrypsin deficiency No

Rare Partners sarl No

Baxter No

Dompé No

FoldRx No

F. Houÿez 25/05/2012 9

In case “no”, why?

� Could not apply before due to the lack of GMP certificate for

production facilities.

– Certificate granted recently though Administrative obstacle and lack of

experience for some countries

� Proof of concept studies for 2 orphan indications not started

� The development stage of compounds has not reached yet a stage

where a CUP may have been envisioned

� Expanded access programs will be discussed once preliminary

efficacy has been demonstrated

� Final decisions have not been made on initiating a program

� New for the company, bureaucracy

� Company was founded in March 2010, not yet involved in a CUP

F. Houÿez 25/05/2012 10

11/14 products marketed within the last 3 years

F. Houÿez 25/05/2012 11

9 products, 42 countries, 74 programmes

F. Houÿez 25/05/2012 12

74/378 = 19,6%

of the potential was

achieved

23/42 countries: 1-2 programmes

F. Houÿez 25/05/2012 13

More than 3034 patients total

F. Houÿez 25/05/2012 14

Detailed figures/country only for 3

Johnson & J, Pharma Mar Genzyme

Austria 0 6 36

Belgium 2 232 46

Croatia 0 0 13

Czech

Republic1 0 67

Cyprus 4 0 0

Denmark 0 0 15

Estonia 10 0 3

France 0 452 60

Finland 0 0 9

Germany 2 135 166

Greece 0 7 12

Hungary 0 0 55

Iceland 0 0 1

Ireland 0 1 4

Italy 22 266 180

Latvia 1 0 10

Lithuania 21 0 13

Luxembourg 0 0 1

Netherlands 9 5 18

Norway 0 4 4

Poland 12 1 75

Portugal 0 5 26

Romania 1 0 0

Russia 0 0 4

Slovakia 0 0 3

Slovenia 0 0 0

Spain 16 290 125

Sweden 0 0 13

Switzerland 1 42 37

UK 23 123 253

total 125 1569 1249

Johnson & Johnson: decitabine

Pharma Mar: Yondelis®

Genzyme: Mozobil®

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Other companies in other

diseases areas provide

patients’ organisations

with weekly data, country

by country, and hospital by

hospital.

Transparency matters.

Not much discussion with POs

F. Houÿez 25/05/2012 16

Were data collected via CUPs?

F. Houÿez 25/05/2012 17

Which type?

F. Houÿez 25/05/2012 18

Impact on information gained

Exposed in

pivotal studies

Exposed in CUP

and safety data

collected**

Eusa Pharma vandetanib 288* 442

Pharma Mar Yondelis® 266 1569

Johnson &

JohnsonDecitabine 303* 125

Genzyme Mozobil® 298 1249

Total 856 3385 (+320%)

* estimates from phase III trials recruitment goals

** not all prior to benefit/risk evaluation

NB: for Carbaglu®, no pivotal studies.

All data from clinical files obtained via compassionate use programme

F. Houÿez 25/05/2012 19

For what use?

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Completed programmes (1)

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Completed programmes (2)

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Completed programmes (3)

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Completed programmes (4)

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Completed programmes (5)

F. Houÿez 25/05/2012 25

More thinking needed on:

� When to start a CUP

– End proof of concept? Even before?

– By the Go/No Go decision?

– With or without preliminary efficacy data?

– When agreement signed with the MAA if different from initial

developer?

� In short: when is a compound becoming a potential medicine?

F. Houÿez 25/05/2012 26

Thank you to

Karel Verkoelen Genzyme

Lode Dewulf UCB

Anne De Bock AstraZeneca

Paolo De Angeli Chiese Pharmaceutici

Federico Fucetola Dompé

Emmanuelle Lecomte-Brisset Eusa Pharma

Bill Aliski FoldRx Pharmaceuticals

Paolo Morgese Merck Serono

Olivia Maurel Novimmune

Marie-Christine Fortun Orphan Europe

Virginia Cuervo Pharma Mar

Germano Carganico RarePartners Srl

Peter Myrenfors Swedish Orphan Biovitrum

And Baxter, Talecris Biopharmaceuticals

Fabrizia Bignami Eurordis

Blanca Vera Gargallo Eurordis

Emmanuel Chantelot EBE/Europabio

supported by

The responsibility of

the content of this

report lays with

EURORDIS. The

Executive Agency is

not responsible for

any use that may be

made of the

information

contained therein.

F. Houÿez 25/05/2012 27

Thank you.

F. Houÿez 25/05/2012 28

(C) Roll-over study(A) Clinical trials: experimental drug

(B) Clinical trials: placebo or control

CT recruitment

terminates

(E) Open label study, named patient basis, cohort…

(D) Parallel access / track

Patients representing an unmet

medical need or with no suitable

alternative available, and/or not

eligible for CT

Patients eligible

for clinical trials

(CT)

All patients with

same disease in

countries with CT

All patients with

same disease in countries with

no CT

Patients representing

an unmet medical

need or with no

suitable alternative

available

(F) Open label study, named patient basis, cohort…

(G) Patients treated

via marketing

authorisation

(H) Financial

Assistance

Programme

(I) Import

authorisation

When a marketing

authorisation is granted

When there is no marketing

authorisation

(J) Humanitarian

access

(K) Compulsory

licensing

(M) No treatment

Compassionate Use

Programme = (C) +

(E) + (F)

Expanded Access

Programme =

CUP + (D) + (I) + (J) +

(K) +…

(L) Off-label use

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