Marlene E. Haffner, MD, MPHCEO, Haffner Associates, LLC

Center for Drug Research and DevelopmentU of British Columbia

Vancouver, CanadaTuesday, October 16, 2012

◦ Patentexpiration◦ GenericCompetition◦ DryingPipelinesy g p◦ Biosimilars◦ RegulatoryGuidelines

◦ ReductioninROI◦ LackofSuccessE i U i◦ EconomicUncertainty

• Limitedpublicawareness invisiblepatientpopulationf l l d f d• Scarcityofclinicalexpertiseandreferencecenters– diseaseis

poorlyunderstood;nonaturalhistory• Delayindiagnosis• Smallpatientpopulation– difficultyinrecruitingtoclinicaltrials

• 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 malignant lymphoma 30Non Hodgkin malignant lymphoma 30

Retinitis pigmentosa 28

Gelineau disease (Narcolepsy) 26

M l l i l 25Myeloma, multiple 25

Alpha-1 antitrypsin deficiency 25

Diaphragmatic hernia, congenital 25

Source: Orpha.net

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

Designation

th

◦ chair 1 from each MS 3 patient organization members 3◦ chair,1fromeachMS,3patientorganizationmembers,3fromCHMP,1eachNorway,Lichtenstein,Iceland,1fromEC

Ph l Aff L A d 1993◦ PharmaceuticalAffairsLawAmendment 1993

Nation Programs Challenges

India IndianDrugsManufacturesAssociation 2001 requestedthegovernmenttoinstitutetheOrphanDrug Act

EnforcingPatentLawsandMarketexclusivity

DrugAct.

Taiwan RareDiseaseandOrphanDrug Act 2009159classifiedrarediseases77approvedorphanproducts

Regulation EfficiencySafetyMeasuresLocaldrugdevelopment

SouthKorea Designation Prevalence 20,000anddiseaseswithnotreatmentinKorea130Orphanproductsapproved

RegulationthroughKFDAUsage limitations

HongKong NewChemicalEntityRegistrationProcess Process Time

Singapore Singapore’sMedicineAct‐Inactive Definitionisunclear;thereismentioningyetnodetails

South Africa South African Foundation for Rare Disorders No strength compliance fundingSouthAfrica SouthAfricanFoundationfor RareDisorders No strength,compliance,funding

Australia Designation Prevalence 2,000Focusedonparticularpopulations

Notdefinedinlaw

Source: Sharma, Abraham, Manas, & Dushyant. "Orphan Drug: Development Trends and Strategies."

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 d d li i C d FDA-approved drug license in Canada

Canadians pay an estimated $82 million/year on orphan drug†drug†

Concerns re price and QALY

Alberta◦ First to develop Rare Diseases Drug Program on April 1, 2009◦ Defines orphan as less than 1 in 50,000◦ Program only covers drugs for five rare diseasesg y g

Ontario◦ Defines orphan as 1 per 100,000-150,000◦ Framework developed January 2010◦ Framework developed January 2010◦ Ministry created an expert review process to help align

potential patients with available OD therapiesH il d d t P i i l P bli D Pl Heavily dependent on Provincial Public Drug Plans◦ Budget constraints◦ Other provinces? p

All th di t ib ti f d th t il bl f Allows the distribution of drugs that are unavailable for sale to medical personnel (Emergency)

Provides access to treatments for rare disorders Provides access to treatments for rare disorders Provides legal accesses – no safety assurance Requires reporting of all outcomes Requires reporting of all outcomes Drugs Directive Renewal Process◦ Special Access Program (1996)◦ Preauthorization Waived◦ Physician Awareness

P i it R i Priority Review◦ First entry new active substance◦ Serious, life-threatening or severely debilitating disease or , g y g

condition◦ Important therapeutic Gain

Conditional Approval◦ Post –marketing confirmatory studiesPost marketing confirmatory studies◦ Non-renewal

Investigational New Drugs◦ Review process that oversees the safety of proposed clinical research◦ Provides assistance to manufacturers in clinical trial designation and

developmentp Drug Evaluation Fees Regulation◦ Provision for the reduction of fees for drugs in smaller marketsP t t P t ti Th P t t A t Patent Protection, The Patent Act◦ 20 years from file data◦ No patent term extension

Research & Development Incentives, The Income Tax Act◦ Provides tax credit to R&D for the advancement of science

Finding of Rare Disease Genes in Canada Funded by Advancing Technology Innovation through

Discovery Consortium of doctors and scientist Consortium of doctors and scientist Lead by University of Ottawa, University of British

Columbia, Research Center CHU Sainte-Justine Goals◦ Identification of patients◦ Identification of disease-causing genetic changes◦ Identification of disease-causing genetic changes◦ National Data Coordination Centre improve sequencing◦ Ethical guidelines for sequencing

Partnership between Medunik Canada and Orphan Europe di t ib ti tdistribution agreement

Medunik Rights to Market Therapiesp◦ Acute Hepatic Porphyria◦ Patent Ductus Arteriosus◦ Hyperammonaema due To N- acetylglutamate Synthase (NAGS) or 1 ype a o ae a due o N acety g uta ate Sy t ase (N GS) o

of 3 organic acidurias◦ Vitamin E deficiency in Chronic Cholestasis

QOL Medical (2011) QOL Medical (2011)◦ Sucraid (sacrosidase)◦ Ethamolin (Ethanolamine Oleate)

N ti l t k f i ti th t t National network for organizations that represent rare diseases

Provides information on/to support groups Provides information on/to support groups Involved in legislative measures◦ Development of Orphan Drug Policyp p g y◦ Expensive Drugs for Rare Diseases Program

New-born Screening Initiative Director – Durhane Wong-Rieger, PhD

Past approach on Orphan Drug Regulation New modern framework (Oct. 3, 2012)◦ Development, Evaluation, and Approval

h fi i i / i i Orphan Definition / Criteria Key focus◦ International collaboration (information sharing)◦ International collaboration (information-sharing)◦ Resource Efficiency for Canadian Scientist◦ Improved safety and effectiveness monitoring

Benefits – so far – no exclusivity or tax incentives Timeline - will go for public consultation

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 specialized clinics / expert centers specialized clinics / expert centers medical laboratories ongoing research / clinical trials patient organizations Registries/ biobanks◦ Create a national entry site to OrphanetCreate a national entry site to Orphanet

Relative contribution of Top-15 countries to the total i tifi t t f th 88 t b li di d †scientific output for the 88 rare metabolic disorders†

1996‐1998 2009‐2011

OUT

IN

† De Vrueh, Remco. "China Has Joined the Fight against Rare Disorders."

◦ Productmustbesafeandeffectiveforitsintendeduse◦ Not always easy to demonstrate◦ Notalwayseasytodemonstrate◦ Frequentpost‐marketingcommitments

◦ 80%genetic◦ 90%Seriousand/orlifethreatening US ;100%

serious/lifethreatening EU◦ 50%children

◦ EU has white paperEUhaswhitepaper

◦ FDAwillhaveguidance

◦ Founder effect◦ Foundereffect

◦ Culturalnorms

Protocolassistance/pre‐INDmeetings– usedinUSandEUandJapan.Nocharge

FDA– OfficeofOrphanProductsReviewsdesignationand Review Division grants product approval ConsultandReviewDivisiongrantsproductapproval.Consultwitheachother.OfficeofRareDiseasesinCDER– workswithorphanproductpolicyinCDER

EU– COMP reviewsdesignationwithconcurrencebyEC.ApprovalbyCHMP withconcurrencebyEC

Concordance between EU and US probably 90% ConcordancebetweenEUandUSprobably 90%◦ Differenceswithdiseasedefinition◦ Andpopulationnumbers

PDUFA5/FDASIA– SectionIXT l ff f d d◦ Toimplementmoreeffectiveprocessesforexpediteddevelopmentandreviewofinnovativenewdrugstomeetunmetneeds § 901 a

◦ HelpfulforOrphanProducts

◦ HelpfulfornewFDAreviewers

BigPhRMA increasinginvolvementinOrphanProductDevelopmentp

AsianMarkets‐ emerging Genetherapy– onthehorizon Improvements in Diagnosis/Treatment/genetic markers ImprovementsinDiagnosis/Treatment/geneticmarkers NeedformoreNaturalHistoryData IssuesofAccess/Cost‐ especiallyinindividualMemberStatesStates

Newplatforms Chronictherapy– longlivedproductsC d h d il bl b Canadahassomeproductsavailable,but….

Overall‐ exciting,newtechnology,servingunmetneedsformillionsworldwide!

Marlene E. Haffner, MD, MPH, ,President & CEO

11616 Danville DriveRockville Maryland 20852Rockville, Maryland 20852

mhaffner3@verizon.netwww.mhaffner.com

301 984 5729 - office301 641 4268 - cell301 984 2272 - FAX301 984 2272 - FAX