effective late stage pathways for biosimilar products · 2019. 1. 16. · biosimilar compound...

© 2017 PAREXEL INTERNATIONAL CORP.

EFFECTIVE LATE

STAGE PATHWAYS

FOR BIOSIMILAR

PRODUCTS

Dr. JingPing Yeo

Corporate Vice President, Clinical Research

Services, PAREXEL International

February 17th, 2017

PAREXEL India Symposium 2017

© 2017 PAREXEL INTERNATIONAL CORP. / 2

AGENDA

EFFECTIVE LATE STAGE

PATHWAYS FOR

BIOSIMILAR PRODUCTS

• Enhancing operational efficiencies of

Late Phase Biosimilar trials

• Optimizing patient recruitment and

retention strategies

• Investigator interest

• Acquiring the reference product and changes in

the reference product

• Leveraging data driven monitoring for

data surveillance in Biosimilar studies


SEAMLESS OPERATIONAL INTEGRATION

Strategic Development Clinical Trials Marketing Approval

Consulting

Development Plan

Commercialization

Plan

Early Phase

Phase I

Global Clinical

Research Services

Phase III

Consulting

Regulatory

Filings

Create aggressive defensible

development

plans and gain

Agency buy-in

Maximize ROI

through a compelling value

proposition

• Overcome local regulatory and operational hurdles • Optimise patient access – “global reach” • Optimize operational efficiencies and risk

management via integrated technologies

• Direct experience in the preparation and submission

of Biosimilar CTDs that resulted in

approval

• Negotiation of Phase IV commitments (risk management)

• Implement risk sharing program that drives speed & efficiency

• Implement dedicated leadership & expertise model


BIOSIMILAR COMPOUND GLOBALIZATION ROADMAP

Phase III in US, Europe & Asia (>500 subjects)

• Therapeutic equivalence (safety and immunogenicity)

• 2 arms

• Investigational product – xx subjects

• Reference product (EU sourced) – xx subjects

Global market access

• Leverage the Phase I and Phase III study to apply Asia & EU MAA

• Leverage EU MAA to apply for most emerging market MAA without or limited

additional studies (local patients required in India, Russia, Mexico, Japan, Korea)

Phase I & Phase Ib PK in a particular country

• PK Equivalence in specific patient population

• 2 arms

• Investigational product – xx subjects

• Reference product (EU sourced) – xx subjects


ACCELERATING THE PHASE III STUDY

• Conservative Plan (Long overall timeline, Low risk if true no similarity)

• Aggressive Plan (Short overall timeline, High risk if true no similarity)

• Relative aggressive and Control the risk

• Aggressive Plan and minimized the overall sample size

Phase Ia

Phase Ib PK

Phase III

Phase Ia

Phase Ib PK

Phase III

Phase Ia

Phase Ib PK

Phase III

Phase Ia

Phase Ib PK/ Phase III


OPERATIONAL CONSIDERATIONS

Understanding the regulatory environment

• Early engagement of regulators (open to negotiation)

• Manage the specific requirements of IRB/EC

– Work closely with sites, lab to collect required documentation

• Identify phase III sites in parallel with preclinical/Phase I work

– RA and IRB/IEC submissions made in parallel

– Consider early Phase III submissions

• Appropriate patient population and sample size

– Required designs not set in stone; early health authority input is critical

– Limited relevance of original innovator’s basis of approval

– Safety as a factor for sample size

Knowing the “right” sites and engaging the investigators


OPERATIONAL CONSIDERATIONS (2)

Ensuring quality data and compliance

• Contingency plan in monitoring plan for missing data

• Clear guidelines on SD requirement, CRF completion and protocol deviation management

• Leverage data driven monitoring technology & data surveillance tools

• Comprehensive/continuous training, tools and lessons learned to sites

Identifying the right clinical endpoints

• Include biomarkers or other surrogates predictive of clinical efficacy

Selecting the reference products

• Obtain from a combination of sources

• May need to demonstrate in-vitro comparability to multiple sources


KEY SUCCESS FACTORS IN PATIENT ENROLMENT

Proactive engagement with sites

Accelerate site start-up and site activation

• Weekly Prescreening log

• Offer site support – e.g., via SMOs

• Study level documentation in English, localized in each country

Investigator relationship and retention is key

• Bi-weekly enrollment status letter to all PIs, and Weekly booster call by CRA

• Engage the sites at identification and qualification phase

• Emphasize the study benefits including the extension study

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, need to educate on safety and efficacy

Make effective use of Asian countries

Leverage on established footprint and infrastructure


IDEAL SITE CRITERIA

Key Factors

• Does the site have this patient population?

• Is the site correctly aligned to the protocol

criteria?

• Investigators with affiliation to country

therapeutic groups/disease networks

• The number of studies that PI conduct in

parallel?

The “Right” Sites

• Sites that routinely treat specific indication patients

with biologic agents

• Sites that PAREXEL has a working relationship with,

or has pre-identified, including good-performing sites

from the previous biosimilar studies

• Investigators with affiliation with strong network of

indication working groups

• Centers that have an adequate facility to conduct

clinical trials for patients (e.g. chest x-ray, ESR

measurement etc.)

PATIENT EXPERIENECE & TECHNOLOGY PATIENTS MAKE INFO MORE TRANSPARENT,

ACCESSIBLE, PATIENT FRIENDLY • Improve participation

& experience

• Reduce patient

burden

• Innovate data capture

Difficult to:

• Identify sites

• Engage in a

meaningful

conversation


PATIENT ENROLLMENT/RETENTION STRATEGY

Newsletters Referrals Patient Materials /

Others Resource /

Compensation Booster Actions

• Give a heads-up in

advance to

investigators to

assign sufficient

Sub-Is/ SCs

• Increased

investigator fee for

high enrollers

considering the

workload of site staff

• Assign more CRA

hours for high

recruiting sites to

provide more site

support.

• Compensations to

patients for

transportation fee

• Recommend

‘Meetings within

hospital’ to create

awareness amongst

colleagues on regular

basis.

• Laminated charts for

trial design and trial

flow chart for easy

reference

• Dear Doctor letter to

other doctors within

the country explaining

Study

• Prepare and distribute

newsletters on a

regular basis with up

to date study updates

• Highlight enrollment

• Newsletters to

address enrollment

issues and major

changes/ updates to

the study procedures

• Targets - high

enrollers –

Appreciation and

Recognition!!

• Patient retention

status update

• Close contact with

the sites weekly

during start-up to

keep continued site

engagement

• PL/COL/sponsor

visits sites, discuss

with PI to motivate

• Interim SC or local

investigator meeting

(experience sharing

from high recruiters

or good performance

sites)

• To share with PI the

publication policy

during SIV, if

applicable

• Patients facing tools:

poster, study

brochure, etc.

• Identify Back-up sites

at the beginning and

get those initiated if

applicable

• Patient retention

materials;

appointment

reminder card, etc.


LEVERAGING DATA DRIVEN MONITORING

(Off site &

centralized monitoring)


Improved data quality and patient safety

RISK-BASED OPERATIONAL STRATEGY

Design • Protocol Optimization (Design)

• Data Driven Site Placement

• Data Driven Patient Recruitment

Risk

Avoidance

Execution • Mitigation & Contingency Planning

• Adaptive Monitoring & Data Surveillance • Ongoing Risk Measurement

Risk

Monitoring

Delivery Outcomes • Risk at Acceptable Levels

• Mitigation & Triggered Contingency Deployment

• Data Driven Operational Interventions

Risk

Mitigation

DATA-DRIVEN OPERATIONAL STRATEGY CONTINUOUS FOCUS ON RISK MANAGEMENT

Risk

Assessment

Assessment • Identification of Risk

• Analysis of Risk

• Evaluation of Risk

Da

ta S

urv

eil

lan

ce

Te

am

Project Lead

Global Clinical Operations Lead

Data Management Lead

Medical Monitor(s)

Biostatistics Lead

Primary Statistical Programmer


RISK CATEGORIES

Data Quality

Data timeliness

Milestone delay

Protocol Adherence

Site Management Quality

Site Visit compliance

Subject Safety

DDM APPLICATION RISK CATEGORIES


EXAMPLES OF RISKS IDENTIFIED – FROM DDM

High risk sites

0.00

0.50

1.00

1.50

2.00

2.50

3.00

3.50

4.00

4.50

5.00

Total

Data Quality

0.58

Data Timeliness

0.54 Protocol

Adherence

0.07

Site visit compliance

0.81 Subject safety

0.24

Site

management

Quality 0.98

Delay milestone

3.07

Risk Categories

Ris

k s

co

re


DATA SURVEILLANCE – COUPLING WITH TECHNOLOGY

• Standard library includes

+60 visualizations focused

on safety parameters

across 17 SDTM domains

• Visualizations align with the

Data Surveillance Plan

• Output can be accessed by

sponsor on continuous

basis


RISKS IDENTIFIED – FROM DATA SURVEILLANCE

Inclusion/Exclusion Criteria Not Met - overall trends

INC 4. ECOG performance status of

0-1 at Screening.

INC 6. At least one measurable

lesion according to RECIST v1.1.

EXC18. Any of the following events

within 6 months prior to Screening

EXC 20. Serologically confirmed

active or chronic disease

Action: re-train investigator (as anticancer

agents are prohibited within the study

treatment). Only anticancer agents should be

reported with correspondent indication.

Supportive treatment agents should not be

reported as “anticancer”

Con Meds Distribution by Country


GAME CHANGER

• Race to launch biosimilar products will intensify

• Careful strategic planning and understanding of operational challenges

are critical

• Innovative trial designs needed – to reach biosimilar endpoints sooner

• Leverage on innovative platforms (Data Driven Monitoring) to optimise

study execution and deliver results of high scientific and statistical

integrity

© 2017 PAREXEL INTERNATIONAL CORP. / 18 © 2016 PAREXEL INTERNATIONAL CORP. /

THANK YOU

CONFIDENTIAL 18 © 2017 PAREXEL INTERNATIONAL CORP. /

THANK YOU

CONFIDENTIAL 18

effective late stage pathways for biosimilar products · 2019. 1. 16. · biosimilar compound...

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