The  Orphan  Drug  Framework    for  Canadians    

What is an orphan drug used for? Orphan drugs are used to treat rare diseases which:

•  are life-threatening, seriously debilitating or both serious and chronic in nature

•  affect a relatively small number of patients (less than 5 in 10 000, but typically closer to 1 in 100 000)

•  are often genetically based, onset at birth or early childhood, lead to a shortened life-span

•  reduce quality of life and place a heavy burden on caregivers and the healthcare system

•  are difficult to study because of the small patient population

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Objectives of the Orphan Drug Framework •  channel orphan drugs into a federal regulatory pathway designed to improve

market availability in Canada

•  draw on new post-market and transparency powers from Vanessa’s Law

•  reflect Canada’s legislative and regulatory context, while aligning where possible with other international regulators’ orphan drug frameworks

•  encourage the generation of knowledge regarding rare diseases in drug development through an open and transparent regulatory environment and the provision of advice to companies developing orphan drugs

•  allow for accelerated market authorization

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Key Components of the Framework Orphan drug designation certificate

• The designation process will:

–  publicly identify medically plausible drugs for rare diseases (orphan drugs) –  enable early consideration of medically plausible drugs by payers for purposes of

improving patient access •  Alerting the health care system that the drug is promising •  Allowing early consideration of evidentiary needs for the system and transmission of them to

drug developers (federal – clinical trial and market authorization requirements; provincial – reimbursement)

–  align with key international pathways and have a special pathway for drugs that have already received designation for the same indication from the United States Food and Drug Administration (US FDA) or the European Medicines Agency (EMA)

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Key Components of the Framework Regulator’s Advice • Drugs with orphan designation will be eligible for formal, written regulator’s advice for clinical trials, the potential balance of pre- and post-market evidence requirements, and the development of post-market plans

• Health Canada will facilitate joint advice where possible and requested by sponsors –  with international regulators –  with Canadian health technology assessment (HTA) bodies

Market Authorization Applications The market authorization application process promote an abbreviated pathway for drugs for ultra-rare diseases that are already approved by the US FDA or EMA under existing framework for use of foreign reviews:

–  A disease is considered ultra-rare if it affects not more than 5 in 100,000 persons in Canada –  Abbreviated data requirements for market authorization applications for these drugs –  Health Canada’s review of drugs for ultra-rare diseases will be based on the regulatory decisions

made by the US FDA or EMA in their reviews –  Aims to encourage manufacturers to submit applications for drugs and improve the availability of

drugs for patients suffering from extremely rare diseases

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Key Components of the Framework Post-authorisation market plans •  application will include a post-authorization plan to:

Ø  characterize, monitor and continue to identify and assess the harms and benefits associated with the orphan drug, and

Ø  manage the uncertainties relating to those harms and benefits

•  Includes: enhanced post-market surveillance procedures, regular monitoring of the terms and conditions associated with market authorization, risk management plan, confirmatory studies, etc.

•  Timelines for fulfilling the measures, reporting on progress and submitting results to Health Canada

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Key Components of the Framework Transparency

•  Transparency throughout the life-cycle of the drug:

–  at designation: screened-in application for a named disease and anticipated therapeutic benefit; name of company and drug upon issuance of designation

–  at market authorization: screened -in application of named drug from named sponsor for named indication; at issuance, additional details including summary of post-market plan and any terms and conditions imposed on the market authorization

–  post-market: transparency at key points, such as amendments to the market authorization, post-market plan, and terms and conditions

–  positive and negative regulatory decisions and the reasons for them, including: issuance and refusal of a certificate of designation, issuance and refusal of a market authorization, reassessment, suspension or revocation of a market authorization

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Patient Involvement

•  The Orphan Drug framework seek public input into the review of submissions for orphan drugs.

•  In December 2013, Health Canada endorsed a patient involvement pilot project:

–  What it is: •  A simulation of how patients, caregivers, health care professionals and patient

groups could be involved at the anticipated market authorization stage for orphan drugs

•  Allow Health Canada to manage expectations and gauge stakeholder (patients, caregivers, patient groups, health care professionals, drug sponsors) and reviewer satisfaction with the pilot project and make adjustments as necessary

•  Help minimize the risk of errors and contribute to the Department’s readiness to use patient involvement information

Patient Involvement Pilot Project

•  A simulation of how patients will be involved at the market authorization stage

•  Two sponsors/drugs (one pharmaceutical and one biologic)

•  Surveys posted on Health Canada’s consultation website (access limited to pilot participants)

•  Recruited patients, caregivers, health care professionals and patient groups through Canadian Organization for Rare Disorders (CORD) and other disease specific patient groups.

Life-cycle Approach What is known about the potential/actual benefits, harms and uncertainties associated with a drug changes over time

Current: Limited point-in-time oversight based on applications for clinical trials and marketing authorizations.

Future: Expanded and continuous oversight beginning at early development stage with medical plausibility and encompassing a greater ability to define post-approval information gathering.

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The Orphan Drug Life-Cycle

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Vanessa’s Law •  Vanessa’s Law amends the Food and Drugs Act improving Health Canada’s

ability to: –  collect post-market safety information –  take appropriate action when a serious risk to health is identified

•  These amendments are particularly important in the rare disease context

where often times: –  many of the patients impacted are vulnerable paediatric populations –  information on the drug and the disease is sometimes limited

•  Powers that will be incorporated into the Orphan Drug Framework

–  Terms and conditions on a market authorization –  Transparency including making positive and negative regulatory decisions publicly available

•  Opportunities for structured patient involvement –  Reassessment –  Mandatory label changes –  Mandatory notification of foreign risk information –  Tests and studies

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Next Steps •  Briefings to Minister’s Office on project

•  A Guidance Document on new framework has been completed

•  Timelines for consultations not yet confirmed

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Thank You/Merci!

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