Durhane Wong -Rieger, PhD

President, Canadian Organization for Rare

Disorders

F e b r u a r y 2 0 1 4

Orphan Drugs Improving Treatment for Rare and Genetic Cancers

Key Points

Rare Cancers “not so rare”

Genomic-defined cancer subtypes leading to targeted therapies

Effective therapies for rare cancers based on genetic defect

Canada’s Orphan Drug Regulatory Framework to support R&D and access to rare disease drugs

Lifecycle approach– from clinical trials to real-world use

Managed Entry Programs—Right drug, right patient, right time, right price

Genetic Testing Improves Breast Cancer Odds

Gene mutations BRCA1 & BRCA2 increase risk breast & ovarian cancers

5 -10% breast & 15% ovarian cancer = screening & prevention

HER2-positive accounts for 20% breast cancers

Specific treatments to kill HER2 cells: Herceptin and Tykerb

Scanning whole genome (DNA testing) can identify frequent and rare genomic cancer alterations and target appropriate drugs

ID genetic aberrations advanced breast cancer; match therapies

Whole-genome analysis of 423 patients ID genetic alterations in 2/3

46% had targetable genomic alteration; 39% had rare alteration

28% with targetable alterations matched with treatments already in clinical trials

Lung Cancer: Genetic Typing Improves Odds

2nd Most Common:

25,500 new cases and 20,200 deaths in 2013

Common profile: 50 year-old males, smokers

About 2/3 = non-small-cell lung cancer (NSCLC)

Treatment = surgery, chemotherapy; survival < 70% at 5 years

About 4% NSCLC have genetic ALK-mutation (kinase activity)

Patients generally younger and nonsmokers

900-1,000 ALK+ Canadians per year

Xalkori (Crizotinib) inhibits ALK activity

Response rate (tumour stabilized or shrinkage) = 67-90%

3 year progression-free survival = 63% (one LT study)

3 year overall survival = 72% (one LT study)

Drug Information Association www.diahome.org 5

Rare Cancers Not So Rare

RARECARE definition (incidence <6/100,000/year) Annual incidence rate of all rare cancers (in Europe) was about

108 per 100,000

About 186 known rare cancers (in Europe)

22% of all cancer diagnoses (new cases)

24% of all cancer prevalence (total cases)

Five-year relative survival was on average worse for rare cancers (47%) than common cancers (65%)

Drug Information Association www.diahome.org 7

Most “Common” Rare Cancers

Uterine cervix and thyroid carcinoma are rare according to the incidence (RARECARE) criterion and ‘common’ according to the prevalence criterion.

Six cancers are common according to the incidence criterion and rare according to the prevalence criterion: Stomach adenocarcinoma,

Pancreatic adenocarcinoma,

Lung adenocarcinoma,

Lung squamous cell carcinoma,

Poorly differentiated endocrine carcinomas of lung and

Group othernon-Hodgkin mature B cell lymphomas.

Treating Myelofibrosis: Rare Leukemia

Leukemia fairly common

5,800 Canadians will be diagnosed with leukemia.

2,600 Canadians will die from leukemia

Myelofbrosis = 1.5/100,000

Median survival of 3 years

50% have genetic defect: JAK2 inhibitor

Ruxolitinib (Jakafi) (approved in 2011) addresses JAK2

Early results = 52% reduction in risk of death

Overall survival increased (81% compared to 61%)

Marketing and Access Challenges for Rare Diseases

without Orphan Drug Policy

No definition, no orphan drug policy; few orphan drugs. Prior to 1983, only 10 new drugs approved worldwide for rare

diseases

Many Orphan Drugs in USA and EU In USA: about 425 products in 30 years since Orphan Drug Act

In EU: about 100 new orphan drugs in 13 years

Benefit: estimates of up to 15 million people

Canadian patients have NO access to half of these drugs Canada has approved 47% of orphan drugs licensed in USA

Canada has approved 51% of orphan drugs approved in Europe

Concerns over separate, slow approval; lack reimbursement

3/13/09 Data Uncertainty/Rare Disorders

10

NEW Orphan Drug Framework

OD designation criteria and processes aligned with US and EU

(promote collaboration)

Formal advice for clinical trials (Canada and/or international),

including design, sample, outcome measures, follow-up plan

Transparency and information sharing throughout drug lifecycle,

available to HCPs, HTAs, and patients to inform decisions

Posting of orphan drug designations, clinical trial registration,

market authorizations and post-market plans

Life-cycle approach to accommodate evidence from multiple

sources before and after a drug is marketed

May 2010 Access to Drugs Canada

11

Life-cycle Approach: Taking into account a wide body of evidence before and after a

drug is marketed

12

Patients, HCPS and HTAs: provide input early stages of drug development on design, benchmarks, outcomes, quality of life (short and long-term)

Industry: (Free) Early protocol advice; priority review, waived filing fees (SMEs); post-market benefit-risk plan; and 8 years of market exclusivity

Researchers and Regulator: Maximize resources, coordinated research w/int’l collaboration and regulatory harmonization, standardization of REB review to eliminate duplication and reduce burden on research community.

Drug Information Association www.diahome.org

13

How Will ODRF Facilitate Entry?

What are Managed (Entry) Access Programs

aka: Risk-sharing schemes, coverage with evidence development, evidence building programs, expanded (exceptional) access programs, named patient programs (individual access), temporary authorizations for utilization

Manufacturers using MAPS for patient access (see Idis)

38% use MAPS for patients not eligible for CTs

64% use MAPS to continue access after CTs

77% use MAPS to provide non-CT patients access while negotiating listing

30% use MAPs to address needs after discontinuing product development

2/27/2014

14

Evaluation Throughout Lifecycle

Drug Information Association www.diahome.org

15

Orphan Drug Lifecycle Approach Supports MAPs

• Orphan (novel) drugs: similar scientific requirements built-in

flexibility for innovative CTs, adaptive designs, surrogate markers,

subgroup analyses

• Pre-Market: Pre-clinical/clinical data, quality, labelling; designation;

regulatory status elsewhere, evidence limitations; post-market data

collection plan

• Authorization: Require gathering and dissemination of information to

reduce uncertainties re: benefits/harms

• Post-Market: Reassess MA; require compiled information, tests or

studies; safety monitoring, label changes

May 2010

16

Cancer Care Ontario Oncology Evidence Building Program

Principles for funding CTs within funded indication

Equitable and timely access to treatments that are safe, offer maximum clinical benefits, and align with best practices;

Ensure coverage decisions are evidence-based, fiscally responsible, and consistent with the OPDP policies

Fair, transparent, and accountable process

Examples of EBP Clinical Trials

Change in dosing/schedule or combination with another agent

Population not funded

For re-treatment

Approved indication but not “cost-effective”

Indication under trial

Same or different pharmacological class as funded drug

Implications for Private Insurers

Most drugs have been covered under private plans but challenges current and future

High-cost for individual therapy

Therapy not “indicated” for rare cancer type

Life-time usage but often no long-term outcome data

CLIHA: In 2013, unique risk-pooling scheme for drugs >$25K/year includes all insurers (full plans)

Challenge: does not include self-insured or ASO

Future: many more drugs in development

50% of orphan drugs for rare and targeted cancers

Requires genetic testing to qualify or optimize

2/27/2014

18

CORD ARCTIC QUEST—August 2011

What can people with rare disorders do? Anything!

Thank You!

Nov 2010 USA CA EU Access to OD

20

Durhane Wong-Rieger, PhD

President

Canadian Organization for Rare Disorders

www.raredisorders.ca

416-969-7435

durhane@sympatico.ca