Managing the Challenges and Opportunities of Breakthrough TherapiesWorkshop
Prudence Scott FRACP MPhil DPhilCo-Director, Haematology/Oncology Evaluation Unit, TGAMedical Oncologist, Monash Health
National Medicines Symposium, 19 May 2016
National Medicines Symposium, 19 May 2016
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
National Medicines Symposium, 19 May 2016
Pathway to registration ‘80s, ‘90s, 2000sPhase 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
National Medicines Symposium, 19 May 2016
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
National Medicines Symposium, 19 May 2016
Targeted therapiesSeamless oncology trials
• PK, PD, efficacy and safety• Expansion cohorts once dose-finding complete• Biomarker assessment
“Phase I” needs a new name:
suggestions?
• Studies of efficacy and safety• Multiple open label, single arm cohorts within Phase II trials - “octopus”• Master protocols• Biomarker validation +/- test development
Phase II
• ConfirmatoryPhase III
National Medicines Symposium, 19 May 2016
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
National Medicines Symposium, 19 May 2016
Accelerated approvals in Haematology/Oncology
• Confirmation of benefit following accelerated approval– 50% confirmed– 40% still underway– 10% benefit not confirmed
reasons
National Medicines Symposium, 19 May 2016
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
National Medicines Symposium, 19 May 2016
Breakthrough designations
338 in total137 (41%) in Haem Onc
38% granted38% denied20% withdrawn
201 (59%) other areas incl rare inherited disorders, ID
National Medicines Symposium, 19 May 2016
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
National Medicines Symposium, 19 May 2016
TGA submissions in Haematology/Oncology Registration in Australia now sought on earlier data for
Haematology/Oncology products
85%2014
75%2015
National Medicines Symposium, 19 May 2016
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
National Medicines Symposium, 19 May 2016
Challenges with early approvals1. 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
National Medicines Symposium, 19 May 2016
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
National Medicines Symposium, 19 May 2016
Summary of breakthrough designation era
Better drugs
Better biomarkers
Less information
National Medicines Symposium, 19 May 2016
Communicating decision to approve on early data1. *Note to the Indication2. *Boxed warning in PI, equivalent in CMI3. 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
National Medicines Symposium, 19 May 2016
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
National Medicines Symposium, 19 May 2016
Post approvalHow can we improve reporting of outcomes to the TGA?• immediately• longer term
How can registries capture efficacy and safety for medicines approved on early data?
How can the TGA communicate any necessary changes effectively to stakeholders?
National Medicines Symposium, 19 May 2016
Post approval
How can we improve reporting of outcomes to the TGA?• immediately• longer term
National Medicines Symposium, 19 May 2016
Post approval
How can the TGA communicate any necessary changes effectively to stakeholders?
National Medicines Symposium, 19 May 2016
Post approval
How can registries capture efficacy and safety for medicines approved on early data?
National Medicines Symposium, 19 May 2016
Post approval
Any other issues?