Marlene E. Haffner, MD, MPH CEO, Haffner Associates, LLC Center

Marlene E. Haffner, MD, MPH
CEO, Haffner Associates, LLC
Center for Drug Research and Development
U of British Columbia
Vancouver, Canada
Tuesday, October 16, 2012
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Patentexpiration
GenericCompetition
y g p
DryingPipelines
Biosimilars
RegulatoryGuidelines
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◦ ReductioninROI
◦ LackofSuccess
i U
i
◦ E
EconomicUncertainty
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Limitedpublicawareness invisiblepatientpopulation
Scarcityofclinicalexpertiseandreferencecenters–
diseaseis
f l
l
d f
d
poorlyunderstood;nonaturalhistory
Delayindiagnosis
Smallpatientpopulation– difficultyinrecruitingtoclinical
trials
Geographic dispersion
Geographicdispersion
Lifethreatening/chronic
Heterogeneousconditions
Difficulttostratify/stage– lackofnaturalhistoryofdisease
Limitedtreatmentavailability
Orphan Disease
Per 100, 000 People
Guillain-Barre syndrome
50
Melanoma, familial
50
Autism, genetic types
45
Scleroderma
40
Focal dystonia
30
Marfan syndrome
30
Non-Hodgkin
Non
Hodgkin malignant lymphoma
30
Retinitis pigmentosa
28
Gelineau disease (Narcolepsy)
26
M
l
li l
Myeloma,
multiple
25
Alpha-1 antitrypsin deficiency
25
Diaphragmatic hernia, congenital
25
Source: Orpha.net
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R&DDrivers
CommercialDrivers
TaxCredits
Favorable reimbursement
R&DGrants
Fewerhurdlesto approval
Filingfeesreducedorwaived
Longer/strongerexclusivity
Shorterdevelopmenttimelines
Lowermarketingcosts
Greater RegulatorySuccess
FasterUptake
GlobalSupport
PremiumPricing
Source: Thomson Reuters Newport
Premium, IMS Health
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Designation
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th
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◦ chair
1 from each MS 3 patient organization members 3
chair,1fromeachMS,3patientorganizationmembers,3
fromCHMP,1eachNorway,Lichtenstein,Iceland,1fromEC
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◦ PharmaceuticalAffairsLawAmendment
1993
Ph
l Aff
L A
d
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Nation
Programs
Challenges
India
IndianDrugsManufacturesAssociation 2001 requestedthegovernmenttoinstitutetheOrphan
Drug Act
DrugAct.
EnforcingPatentLawsandMarket
exclusivity
Taiwan
RareDiseaseandOrphanDrug Act 2009
159classifiedrarediseases
77approvedorphanproducts
Regulation Efficiency
SafetyMeasures
Localdrugdevelopment
SouthKorea
Designation Prevalence 20,000anddiseaseswith
notreatmentinKorea
130Orphanproductsapproved
RegulationthroughKFDA
Usage limitations
HongKong
NewChemicalEntityRegistrationProcess
Process Time
Singapore
Singapore’sMedicineAct‐Inactive
Definitionisunclear;thereis
mentioningyetnodetails
South
Africa
SouthAfrica
South
African Foundation for Rare
Disorders
SouthAfricanFoundationfor
RareDisorders
No strength
compliance funding
strength,compliance,funding
Australia
Designation Prevalence 2,000
Focusedonparticularpopulations
Notdefinedinlaw
Source: Sharma, Abraham, Manas, & Dushyant. "Orphan
Drug: Development Trends and Strategies."
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1 in 12 Canadians has a rare disease (CORD)
Most of the rare diseases go undiagnosed and untreated
No reference in Food and Drugs Act and Regulation
More than ½ of orphan drug products approved in US
& Europe are not available in Canada ($$$)
FDA
FDA-approved
d drug
d
li
license in
i Canada
C d
Canadians pay an estimated $82 million/year on orphan
drug†
Concerns re price and QALY
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Alberta
◦ First to develop Rare Diseases Drug Program on April 1, 2009
◦ Defines orphan as less than 1 in 50,000
g
only
y covers drugs
g for five rare diseases
◦ Program
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Ontario
◦ Defines orphan as 1 per 100,000-150,000
◦ Framework developed January 2010
◦ Ministry created an expert review process to help align
potential patients with available OD therapies
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H
il ddependent
d t on P
i i lP
bli D
Heavily
Provincial
Public
Drug Pl
Plans
◦ Budget constraints
p
◦ Other provinces?
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Allows
the
that
All
th distribution
di t ib ti off drugs
d
th t are unavailable
il bl for
f
sale to medical personnel (Emergency)
Provides access to treatments for rare disorders
Provides legal accesses – no safety assurance
Requires reporting of all outcomes
Drugs Directive Renewal Process
◦ Special Access Program (1996)
◦ Preauthorization Waived
◦ Physician Awareness
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Priority
P i it Review
R i
◦ First entry new active substance
g or severely
y debilitating
g disease or
◦ Serious,, life-threatening
condition
◦ Important therapeutic Gain
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Conditional Approval
◦ Post –marketing
marketing confirmatory studies
◦ Non-renewal
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Investigational New Drugs
◦ Review process that oversees the safety of proposed clinical research
◦ Provides assistance to manufacturers in clinical trial designation and
p
development
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Drug Evaluation Fees Regulation
◦ Provision for the reduction of fees for drugs in smaller markets
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P t tP
Patent
Protection,
t ti The
Th Patent
P t t Act
A t
◦ 20 years from file data
◦ No patent term extension
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Research & Development Incentives, The Income Tax Act
◦ Provides tax credit to R&D for the advancement of science
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Finding of Rare Disease Genes in Canada
Funded by Advancing Technology Innovation through
Discovery
Consortium of doctors and scientist
Lead by University of Ottawa, University of British
Columbia, Research Center CHU Sainte-Justine
Goals
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Identification of patients
Identification of disease-causing genetic changes
National Data Coordination Centre  improve sequencing
Ethical guidelines for sequencing
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Partnership between Medunik Canada and Orphan Europe
distribution
di t ib ti agreementt
Medunik Rights to Market
Therapies
p
◦ Acute Hepatic Porphyria
◦ Patent Ductus Arteriosus
ype a
o ae a due Too N
N- acety
acetylglutamate
g uta ate Sy
Synthase
t ase (N
(NAGS)
GS) oor 1
◦ Hyperammonaema
of 3 organic acidurias
◦ Vitamin E deficiency in Chronic Cholestasis
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QOL Medical (2011)
◦ Sucraid (sacrosidase)
◦ Ethamolin (Ethanolamine Oleate)
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National
that
N ti l network
t
k for
f organizations
i ti
th t representt rare
diseases
Provides information on/to support groups
Involved in legislative measures
◦ Development
p
of Orphan
p
Drugg Policyy
◦ Expensive Drugs for Rare Diseases Program
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New-born Screening Initiative
Director – Durhane Wong-Rieger, PhD
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Past approach on Orphan Drug Regulation
New modern framework (Oct. 3, 2012)
◦ Development, Evaluation, and Approval
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Orphan
h Definition
fi i i / Criteria
i i
Key focus
◦ International collaboration (information-sharing)
(information sharing)
◦ Resource Efficiency for Canadian Scientist
◦ Improved safety and effectiveness monitoring
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Benefits – so far – no exclusivity or tax incentives
Timeline - will go for public consultation
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Reference portal for individuals with rare diseases
Becomes a national team of Orphanet Consortium
In-kind support through Institute of Genetics (CIHR)
Responsibilities
◦ collection of information on
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specialized clinics / expert centers
medical laboratories
ongoing research / clinical trials
patient organizations
Registries/ biobanks
◦ Create a national entry site to Orphanet
Relative contribution of Top-15 countries to the total
scientific
i tifi output
t t for
f the
th 88 rare metabolic
t b li disorders†
di d †
1996‐1998
2009‐2011
O
U
T
I
N
† De Vrueh, Remco. "China Has Joined the Fight
against Rare Disorders."
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◦ Productmustbesafeandeffectiveforitsintendeduse
◦ Notalwayseasytodemonstrate
Not always easy to demonstrate
◦ Frequentpost‐marketingcommitments
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80%genetic
90%Seriousand/orlifethreatening US ;100%
serious/lifethreatening EU
50%children
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◦ EUhaswhitepaper
EU has white paper
◦ FDAwillhaveguidance
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◦ Founder
effect
Foundereffect
◦ Culturalnorms
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Protocolassistance/pre‐INDmeetings– usedinUSand
EUandJapan.Nocharge
FDA– OfficeofOrphanProductsReviewsdesignation
and Review Division grants product approval Consult
andReviewDivisiongrantsproductapproval.Consult
witheachother.OfficeofRareDiseasesinCDER– works
withorphanproductpolicyinCDER
EU– COMP reviewsdesignationwithconcurrencebyEC.
ApprovalbyCHMP withconcurrencebyEC
Concordance
between EU and US probably 90%
ConcordancebetweenEUandUSprobably
◦ Differenceswithdiseasedefinition
◦ Andpopulationnumbers
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PDUFA5/FDASIA– SectionIX
◦ Toimplementmoreeffectiveprocessesforexpedited
T
l
ff
f
d d
developmentandreviewofinnovativenewdrugstomeetunmet
needs § 901 a
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◦ HelpfulforOrphanProducts
◦ HelpfulfornewFDAreviewers
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BigPhRMA increasinginvolvementinOrphanProduct
p
Development
AsianMarkets‐ emerging
Genetherapy– onthehorizon
Improvements in Diagnosis/Treatment/genetic markers
ImprovementsinDiagnosis/Treatment/geneticmarkers
NeedformoreNaturalHistoryData
IssuesofAccess/Cost‐ especiallyinindividualMember
States
Newplatforms
Chronictherapy– longlivedproducts
C
d h
d
il bl b
Canadahassomeproductsavailable,but….
Overall‐ exciting,newtechnology,servingunmetneeds
formillionsworldwide!
Marlene E. Haffner,, MD,, MPH
President & CEO
11616 Danville Drive
Rockville Maryland 20852
Rockville,
mhaffner3@verizon.net
www.mhaffner.com
301 984 5729 - office
301 641 4268 - cell
301 984 2272 - FAX