Biosimilars Webinar June 29, 2016 Slides

Durhane Wong-Rieger, PhD P r e s i d e n t - C a n a d i a n O r g a n i z a t i o n f o r R a r e D i s o r d e r s

Webinar:

Access to biosimilars in Canada

J u n e 2 0 1 6

Cathy Parker D i r e c t o r G e n e r a l – B i o l o g i c s a n d G e n e t i c T h e r a p i e s

D i r e c t o r a t e ( H e a l t h C a n a d a )

Chander Sehgal D i r e c t o r – C o m m o n D r u g R e v i e w a n d O p t i m a l U s e

a t C A D T H

Regulation of Biosimilars (Subsequent Entry Biologics) Biologics and Genetic Therapies Directorate

Health Products and Food Branch

June 2016

Outline

•  The Promise of Biosimilars

•  Canadian Regulatory Approach

•  Challenges

Biologic Drugs

Biologic drugs differ from chemically synthesized drugs as they are •  derived from the metabolic ac8vity of living organisms •  large, structurally complex and difficult to characterize •  inherently more variable •  sensi8ve to light, temperature, and suscep8ble to contamina8on

Differences between pharmaceu8cals and biologics require differences in how they are regulated

Revers and Furczon, CPJ, 2010, 143:134 hKp://cph.sagepub.com/content/143/3/134

Chemical Drug vs. Biologic Drug

What is a Biosimilar?

•  A biologic drug that –  enters the market subsequent to a version previously authorized in Canada –  has demonstrated similarity to a reference biologic drug –  has no clinically meaningful differences from the reference biologic drug

•  A biosimilar relies in part on prior information regarding safety and efficacy due to the demonstration of similarity to the reference biologic drug.

•  Biosimilars are not generic biologics –  Unlike generics, biosimilars are not pharmaceutically equivalent to their

reference drugs (i.e. in comparison with the reference product they do not contain identical amounts of identical medicinal ingredients)

–  Biosimilars can only be shown to be “similar” to a reference biologic drug

The Promise of Biosimilars

•  Minister of Health Mandate Letter – expectations related to improving access to necessary prescription medications and making them more affordable http://pm.gc.ca/eng/minister-health-mandate-letter#sthash.0WH66z0X.dpuf

•  The availability of biosimilars is anticipated to contribute to more affordable biologic drugs, more secure supply and more treatment options

•  Influx of biosimilar submissions expected over next several years as patents and data protection expire

•  Today, there are numerous biosimilar development programs underway and multiple programs for each of the top selling biologics

The Promise of Biosimilars

Rank Leading Products Therapeutic Subclass

2013 Sales in Canada1 ($ millions)

Innovator Company

Canadian Patent Expiry Year

1 Remicade (infliximab) Anti-‐arthritic 694.9 Janssen Biosimilar available

2 Humira (adalimumab) Anti-‐arthritic 434.9 AbbVie

Majority of Canadian patents set to expire between 2016 -‐2020 for leading biologics

3 Lucentis (ranibizumab) Vision loss 402.2 Novartis

4 Enbrel (etanercept) Anti-‐arthritic 332.9 Amgen

5 Cipralex Antidepressant 250.0 Lundbeck

6 Rituxan (rituximab) Autoimmune 217.6 Roche

1 Innovation, Science and Economic Development Canada, “Pharmaceutical industry profile.” Accessed 2 May 2016 https://www.ic.gc.ca/eic/site/lsg-‐pdsv.nsf/eng/h_hn01703.html

Red denotes biologic drugs

Top Selling Drugs (2013)

Biologics made up 5 of the top 10

Expiring patents for all 5

Canadian Regulatory Approach

•  A biosimilar is a biologic drug that enters the market subsequent to a version previously authorized in Canada, and has demonstrated similarity to a reference biologic drug.

•  The demonstration of similarity can be the basis for accepting a reduced non-clinical and clinical data package. –  A biosimilar relies in part on prior information regarding safety and efficacy

due to the demonstration of similarity to the reference biologic drug.

•  Biosimilars are not generic biologics –  Unlike generics, biosimilars are not pharmaceutically equivalent to their

reference drugs (i.e. in comparison with the reference product they do not contain identical amounts of identical medicinal ingredients)

–  Biosimilars can only be shown to be “similar” to a reference biologic drug

Food and Drugs Act

Food and Drug Regula2ons

Guidance Document

Regulatory Approach

Biosimilars are regulated as new biologic drugs in Canada; they are subject to the Food and Drugs Act and Part C, Division 8 of the Food and Drug Regulations just like other new biologic drugs.

Regulatory approach is tailored to the concept of similarity.

A guidance document was published in 2010 to communicate submission requirements to biosimilar sponsors. The document is under revision to reflect experience gained by Health Canada over time.

Regulatory Decision-making •  A final determination to issue an authorization (Notice of

Compliance) is based upon a benefit/risk decision after considering all of the supporting quality, safety, and efficacy data.

Note: This does not differ from any other new drug v  SEBs are considered in new drug status, subject to all the provisions of the

new drug regulations v  Post-market requirements apply v  No declaration of equivalence, interchangeability or substitutability: these

are within the purview of the health care system/s in the provinces

Guidance document •  The 2010 Guidance for Sponsors: Information and Submission Requirements

for Subsequent Entry Biologics (SEBs) was updated in 2015 to reflect experience gained over the last 5 years.

•  Many of the proposed revisions reflect guidance provided by Health Canada to sponsors in relation to submissions or queries.

•  More than 20 unique stakeholders/groups responded –  Individual drug companies, industry associations, patient, healthcare, scientific and

clinical research organizations, law firms

•  Stakeholder comments are actively being reviewed by an internal Health Canada working group.

•  BGTD also launched a three year pilot for SEB Scientific Advice Meetings to allow for discussion and review of quality package by Health Canada early in the development process.

Subsequent Entry Biologics (SEBs) Generic Pharmaceuticals

Nature/Manufacturing process

Biological; derived from living organisms Chemically synthesized

Size, Structure, and Complexity

Large and structurally complex molecules; difficult to characterize

Small molecules, simple and well-defined; easy to characterize

Type of drug submission

New Drug Submission Abbreviated New Drug Submission

Similarity/Equivalence “Similar” to Reference Biologic Drug (Canadian or non-Canadian)

Equivalent to Canadian reference product

Chemistry and manufacturing data requirements

Full quality data plus extensive comparability exercise to show similarity

Full quality data

Clinical data requirements

Clinical trials in patients required comparing SEB to reference product

“Bioequivalence” trials (small trials in healthy volunteers to show that the drug behaves the same way in the body as the reference product)

Extrapolation of indications

Review-based decision on whether to allow for extrapolation to indications held by the Canadian reference biologic drug based on review of detailed scientific rationale or data to support the extrapolation

Automatic extrapolation to all indications of the Canadian reference product

Additional regulatory oversight

Additional regulatory oversight applied to biologic drugs, including SEBs • On site evaluations (inspection of the manufacturing site and drug production) • Lot Release Program

Regulatory review timelines

300 calendar day performance target standard 180 calendar day performance target standard

Interchangeability Authorization is not a declaration of bioequivalence Authorization constitutes a declaration of bioequivalence

International Context

Health Canada EMA FDA Number of biosimilars authorized (as of March 1, 2016)

5 (1st authorized 2009)



•  The European Medicines Agency (EMA) and Health Canada were leaders in the initial development of regulatory frameworks for biosimilars.

•  The US Food and Drug Administration (FDA) has lagged behind other regulators and is now implementing its regulatory framework. There are > 50 biosimilar development consultations underway with FDA.

•  Health Canada works closely with the WHO and other regulators to enable information sharing and to promote regulatory convergence. Regular “cluster” teleconferences with the FDA, EMA, and Japan to discuss specific issues.

Biosimilars authorized in Canada (as of June 2016) Biosimilar Reference

Biologic Drug Therapeutic area Date of NOC

Omnitrope (Somatropin – Human Growth Hormone)

Genotropin Growth Hormone Deficiency in Children and Adult Growth Hormone Deficiency

April 20, 2009

Omnitrope Genotropin Additional indications for Small for Gestational Age, Idiopathic Short Stature and Turner Syndrome

May 8, 2015

Inflectra (Infliximab – Monoclonal Antibody)

Remicade Rheumatoid Arthritis, Ankylosing Spondylitis, Psoriatic Arthritis and Plaque Psoriasis Crohn’s, ulcerative colitis

January 15, 2014 June 10, 2016

Remsima (Infliximab – Monoclonal Antibody)

Remicade Rheumatoid Arthritis, Ankylosing Spondylitis, Psoriatic Arthritis and Plaque Psoriasis

January 15, 2014

Basaglar (Insulin Glargine - Recombinant Human Insulin Analogue)

Lantus Treatment of pediatric (>6 years) and adult patients with Type 1 diabetes mellitus, and adult patients with type 2 diabetes mellitus

September 1, 2015

Grastofil (filgrastim) Neupogen Prevention or treatment of neutropenia December 7, 2015

Challenges - Rapidly Evolving Field

•  Ongoing challenge of regulatory frameworks keeping pace with science •  Close interactions with other regulators and participation in WHO

guideline drafting groups extremely helpful •  Regular review of regulatory guidance document for biosimilars

Challenges - Interchangeability •  Biosimilars are not linked to their reference products in the way

of generic pharmaceuticals. Regulatory authorization is not a declaration of equivalence.

•  Pressures from various stakeholders to provide direction

•  Increased focus on the concept of switching?

•  Confusion in terminology and understanding amongst stakeholders

Subs2tu2on

Automa2c Subs2tu2on

Interchangeability

Switching

Other Challenges

•  Patient and Health Care Provider Confidence –  Perception that biosimilars have less rigid pre and post market data

requirements –  As a new category of drug products there is a need to educate on

their safety and efficacy

•  Naming –  Controversy over whether biosimilars should have unique identifier –  No international consensus. US and Canada support extension to

INN name identifying biosimilars and biologics, EU does not support

•  Labelling –  How much information from reference product’s monograph should

be used in labelling of biosimilar?

Transparency •  Regulatory Transparency and Openness Framework – one of the

objectives is to help Canadians to better understand how and why our decisions are made.

•  Submissions under Review

–  Biosimilars accepted for review are now published on the website •  Regulatory Decision Summaries and Summary Basis of Decision

documents also published

•  Stakeholder registry – to help you stay informed of the latest consultations and participate in any engagement activities. –  Consultation and Stakeholder Information Management System –  Onus to register is on the stakeholder

Contact: Stephanie Hardy Office of Policy and International Collaboration Biologics and Genetic Therapies Directorate Health Products and Food Branch [email protected] Or Catherine Parker Director General [email protected]

Key reference documents •  (Draft) revised Health Canada Guidance Document – Submission and

Information Requirements for Subsequent Entry Biologicshttp://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/consultation/biolog/submission-seb-exigences-pbu-eng.pdf

•  Subsequent Entry Biologics Scientific Advice Meetings Pilothttp://www.hc-sc.gc.ca/dhp-mps/brgtherap/applic-demande/guides/subsequent-entry-biologics-produits-bio-ulterieurs-eng.php

•  Summary Basis of Decision documentshttp://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/drug-med/index-eng.php

•  Regulatory Decision Summarieshttp://www.hc-sc.gc.ca/dhp-mps/prodpharma/rds-sdr/drug-med/index-eng.php

•  Submissions under Reviewhttp://www.healthycanadians.gc.ca/drugs-products-medicaments-produits/authorizing-manufacturing-autorisation-fabrication/review-approvals-evaluation-approbations/submissions-under-review-presentations-cours-examen-eng.php

•  Stakeholder Registryhttp://www.hc-sc.gc.ca/ahc-asc/public-consult/stakeholder-intervenants/index-eng.php

Chander Sehgal D i r e c t o r – C o m m o n D r u g R e v i e w a n d O p t i m a l U s e

a t C A D T H

Patients’ Knowledge and Beliefs about Biosimilars

Durhane Wong-Rieger, PhD Consumer Advocare Network

Patient Survey on Biosimilars

§ WHAT is current status of biosimilars? §  Increasing number of biosimilars approved and available for use §  Increasing evidence about safety, effec8veness, and quality § Uncertainty about long-‐term outcomes and interchangeability

§ WHY were pa8ents surveyed about biosimilars? §  Learn pa8ent knowledge, beliefs, and opinions about biosimilars §  Iden8fy sources of pa8ent and public informa8on §  Engage pa8ents to contribute to evolving understanding of biosimilars

§ HOW will learning from survey be used to engage pa8ents? § Develop up-‐to-‐date informa8on accessible by pa8ents and public § Assure balanced approach to promote informed decision making

How was Survey Implemented

§ Canada-wide Web-based survey § Directed to existing patient cohort of 2,000+

§ Secondary distribution to patient organizations and umbrella associations

§ Promoted through Facebook and Twitter

§ Preliminary Findings (May-June 2016) § Respondents = 320; Complete survey = 200

§ Conditions = inflammatory, blood disorders, immune-related, diabetes, cancers, multi-systemic, lysosomal storage, cardiovascular

Biosimilar Information Sources

0% 10% 20% 30% 40% 50% 60% 70% 80% 90%

100%

Workshop or education forum

about biosimilars

Conference, workshop or forum that

INCLUDED information on

biosimilars

Web-based information

about biosimilars

Written materials about

biosimilars

Public media (newspaper,

magazine, TV, or radio) about

biosimilars

Information from healthcare

providers or healthcare

facility about biosimilars

Which information sources have you used to learn about biosimilars?

Yes

No

Not Sure

Respondents’ Use of Biologics

Familiar with Definition of Biosimilars

Patient Perceptions of Biosimilars

To what degree do you agree that biosimilars compared to original …?


To what degree do you agree a biosimilar as compared to the original …?


Should government regulator, drug plan, HTA, or payer do following?

Attitudes About Use of Biosimilar

Do you agree with statement regarding switching … Avg (1-5)

Same scientific name (INN) implies identical drug 3.3

All biologics should have unique INN or suffix 2.7

Patient should receive exact biologic prescribed 3.1

Patient MAY be switched to biosimilar with consent 3.2

Patient SHOULD be switched if biosimilar lower price 2.1

Patient NOT on original MAY be given biosimilar 3.1

Patient NOT on original SHOULD be given biosimilar 2.7

OK to use biologic for indicators other than approved 2.7

Need monitoring plan to track adverse events 3.5

OK to promote preferential use of biosimilars 1.8

Collect real-world data to update usage guidelines 3.7

Biosimilars save money to allocate to other needs 2.9

1 = disagree completely; 3 = neither agree nor disagree; 5 = agree completely

Summary Patient Attitudes re: Biosimilars - 1

§ Web is most frequent source of information about biosimilars (65%); healthcare provider least frequent (25%)

§ More than half now, in past or in future use biologic medicines; one-fourth will not

§ 2/5 respondents were unfamiliar with biosimilars; 1/5 very familiar

§ About 3/4 to 4/5 believe biosimilars are different and will have different adverse effects than originator

§ About 2/5 believe may substitute biosimilar for originator; about 2/5 believe may NOT substitute

§ About ¼ say okay to extrapolate biosimilar use to other indications of originator even without clinical trials; about ¼ say not okay to extrapolate


§ About ½ agree biosimilar as safe and effective as originator; about 1/3 disagree

§ About 2/3 agree biosimilar could have a different effect than originator

§ More than 4/5 agree could have different adverse effects than originator

§ About 2/5 believe patients should accept a biosimilar if it is much cheaper than originator; 2/5 believe patients should not accept on basis of price

§ About 3/5 would be UNWILLING to switch from originator to biosimilar

§ About 3/5 say it is OKAY to prescribe biosimilar if patient has no experience with originator


§ About 3/5 agree government should approve more biosimilars

§ One-half say should NOT approve biosimilar if originator not approved for use in country

§ Almost 9/10 say government (drug plans) should assure NO interchangeability

§ Almost 8/10 say government (HTA) should NOT recommend switching from originator to biosimilar

§ Almost 100% say patients have right to informed consent

§ Almost one-half say governments should NOT encourage switching on basis of “cheaper” cost; about ¼ agree should encourage switching based on cost

Recommendations

¥ Develop and make available to all patients accurate, balanced

and evidence-based information about biosimilars.

¥ Establish means to address patients’ concerns in open and

honest ways.

¥ Provide tools to monitor patient use of biologics that can

track outcomes to specific biologic.

¥ Develop and implement platforms to collect and analyze real-

world evidence to support and update appropriate use

guidelines.

¥ Engage patients as partners in every step of the process

Resources

§  Market Access and Uptake of Biosimilars (Steering Group of the Process for Corporate Responsibility in the field of Pharmaceutical)http://ec.europa.eu/enterprise/sectors/healthcare/competitiveness/process_on_corporate_responsibility/platform_access/index_en.htm

§  European Medicines Agency Biosimilarshttp://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/document_listing/document_listing_000318.jsp&mid=WC0b01ac0580281bf0

§  Medicines Safety Monitoringhttp://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/general/general_content_000456.jsp&mid=WC0b01ac05801ae8fb

§  Guidance document for patient organisations on EU pharmacovigilance legislation: http://www.eu-patient.eu/Initatives-Policy/Policy/Pharmaceutical-Package/Pharmacovigiliance/

§  Patient Organisations’ Resources The International Alliance of Patients’ Organisations Biosimilars Toolkit https://www.iapo.org.uk/biosimilars-toolkit

§  National Rheumatoid Arthritis Society (UK) Position Paper on Biosimilars http://www.nras.org.uk/data/files/About%20RA/How%20is%20RA%20managed/NRAS%20Biosimilars%20Position%20Paper%20Final.pdf

Contact:

Durhane Wong-Rieger

Consumer Advocare Network

www.consumeradvocare.org

416-969-7435

[email protected]

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