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Presentation: Managing the challenges and opportunities of breakthrough therapies

TGA presentation given at National Medicines Symposium, 19-20 May 2016

30 May 2016

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Presentation

  • Presented by: Prudence Scott FRACP MPhil DPhil
  • Presented at: National Medicines Symposium
  • Presentation date:19 May 2016
  • Presentation summary: To gather input, ideas and feedback on managing key areas for medicines approved on early data.

Transcript

Managing the challenges and opportunities of breakthrough therapies

Prudence Scott FRACP MPhil DPhil
Co-Director, Haematology/Oncology Evaluation Unit, TGA
Medical Oncologist, Monash Health

National Medicines Symposium, 19 May 2016

Slide 1 - Goal of this workshop

  • Foundations stream was asked to address the following:
    • Evidence
    • Safety
    • Knowledge
    • Quality

Goal: gather input, ideas, feedback on managing these key areas for medicines approved on early data.

Slide 2 - Pathway to registration '80s, '90s, 2000s

Phase I, II and III clinical trials

  • Phase I: safety, tolerability, dose selection
  • Phase II: safety, efficacy, dose comparisons in range of cancers
  • Phase III: comparison with existing standard of care, used for registration

Slide 3 - Emergence of targeted therapies 2001

Drug or other substance that interferes with specific molecules involved in cancer cell growth and survival (NCI)

  • 'Driver mutations' or critical pathways
  • Specific populations
  • Biomarkers

Slide 4 - Targeted therapies

Seamless oncology trials

'Phase I' needs a new name: suggestions?
  • PK, PD, efficacy and safety
  • Expansion cohorts once dose-finding complete
  • Biomarker assessment
Phase II
  • Studies of efficacy and safety
  • Multiple open label, single arm cohorts within Phase II trials - 'octopus'
  • Master protocols
  • Biomarker validation +/- test development
Phase III
  • Confirmatory

Slide 5 - Regulatory response to unmet need

1992 FDA accelerated approval

  • unmet need
  • significant benefit over existing therapies
  • surrogate endpoint likely to predict clinical benefit
  • confirmatory data required
  • Label states in indication that approval is based on an early endpoint and may require confirmation

Slide 6 - Accelerated approvals in Haematology/Oncology

  • Confirmation of benefit following accelerated approval
    • 50% confirmed
    • 40% still underway
    • 10% benefit not confirmed
      • reasons

Slide 7 - Regulatory and advocate response to unmet need

FDA Breakthrough Designation 2012

  • Preliminary clinical data suggests a substantial benefit over existing therapies for serious or life-threatening disease or condition
  • Access, support in clinical trial design from FDA
  • Accelerated approval not guaranteed

Slide 8 - Breakthrough designations

  • 338 in total
    • 137 (41%) in Haem Onc
      • 38% granted
      • 38% denied
      • 20% withdrawn
    • 201 (59%) other areas incl. rare inherited disorders, ID

Slide 9 - FDA pathway approvals in Haematology/Oncology

Of 46 new drugs approved in last 4 years (30 in last 2 years!)

  • 17 accelerated approval
  • 29 regular approval
  • 19 had breakthrough designation

Slide 10 - TGA submissions in Haematology/Oncology

Registration in Australia now sought on earlier data for Haematology/Oncology products

  • 2014 - 85%
  • 2015 - 75%

Slide 11 - Opportunities from breakthrough designation

  • Recognition of, resulted from patient voice
  • Earlier approval addressing unmet need
  • Ensures patients have access to optimally designed trials
  • What % of patients enter clinical trials in oncology?
  • Novel clinical trial designs emerging
  • Encourages and fosters innovation e.g. small pharma
  • New ways to use big data to analyse outcomes

Slide 12 - Challenges with early approvals

  1. Rapid product development:
    • Less known about safety and efficacy
    • Multiple trials still to report
    • Biomarker development, validation, testing may still be underway
      • Companion diagnostic vs complementary diagnostic
    • Incorporation of patient-reported outcomes eg PRO-CTCAE, COA Compendium
  2. Collection, communication of post approval information
    • Patients, clinicians, regulators, sponsors, payers
    • Need reporting of adverse events by all stakeholders
    • Effective communication of updates
  3. Timely completion of confirmatory trials and to act upon outcomes
  4. Development of systems to capture big data e.g. INFORMED

Slide 13 - Information exchange and data transformation (INFORMED)

FDA Entrepreneur in Residence program

  • to support meta-analyses and other data explorations that can yield groundbreaking scientific and regulatory insights
  • to create a big data environment comprised of aggregated datasets from:
    • new drug applications (NDAs)
    • electronic medical records
    • wearable technologies
    • social media networks

Slide 14 - Summary of breakthrough designation era

  • Better drugs
  • Better biomarkers
  • Less information

Slide 15 - Communicating decision to approve on early data

  1. *Note to the Indication
  2. *Boxed warning in PI, equivalent in CMI
  3. Statement in Clinical Trials section re evidence base and further trials required to be submitted as condition of registration (similar in CMI)
  4. Conditions of registration
    • Confirmatory efficacy and safety Phase III study/studies
    • Marketing of note to the indication, boxed warning in any promotional materials
  5. Post approval requirements - case-by-case
    • big data/real world data collection e.g. registries - key info for stakeholders
    • patient/doctor information cards
    • health professional educational material

Slide 16 - Goal of this workshop

  • Foundations stream was asked to address the following:
    • Evidence
    • Safety
    • Knowledge
    • Quality

Goal: gather input, ideas, feedback on managing these key areas for medicines approved on early data.

Slide 17 - Post approval

How can we improve reporting of outcomes to the TGA?

  • immediately
  • longer term

How can the TGA communicate any necessary changes effectively to stakeholders?

How can registries capture efficacy and safety for medicines approved on early data?

Slide 18 - Post approval

How can we improve reporting of outcomes to the TGA?

  • immediately
  • longer term

Slide 19 - Post approval

How can the TGA communicate any necessary changes effectively to stakeholders?

Slide 20 - Post approval

How can registries capture efficacy and safety for medicines approved on early data?

Slide 21 - Post approval

Any other issues?

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