Innovation, Uncertainty and Reimbursement Processes in Precision Medicine: The Case of PD-L1

Similar documents
Overview of Biomarker Development for Immune PD-1/L1 Checkpoint Blockade

Transform genomic data into real-life results

Learning from the Impact of the Drug-Diagnostics Strategy in Oncology

Companion & Complementary Diagnostics: Clinical and Regulatory Perspectives

Agilent companion diagnostics for cancer immunotherapy

Patient Leader Education Summit. Precision Medicine: Today and Tomorrow March 31, 2017

Role of the pathologist in the diagnosis and mutational analysis of lung cancer Professor J R Gosney

Regulatory Landscape for Precision Medicine

MICROSCOPY PREDICTIVE PROFILING

Biomarcatori per la immunoterapia: cosa e come cercare Paolo Graziano

CADTH SYMPOSIUM 2016 Scott Gavura, Director, Provincial Drug Reimbursement Programs

Implementation of nation-wide molecular testing in oncology in the French Health care system : quality assurance issues & challenges

The Role of Immuno-Oncology Biomarkers in Lung Cancer

NSCLC. Harmonization study 1. Lung cancer and other malignancies -PD-L1 assay, QuIP EQA

Predictive markers for treatment with Immune checkpoint inhibitors - PD-L1 et al -

Biomarkers for Cancer Immunotherapy Debate

Molecular Testing Updates. Karen Rasmussen, PhD, FACMG Clinical Molecular Genetics Spectrum Medical Group, Pathology Division Portland, Maine

Vernieuwing en diagnostiek bij NSCLC: Immunotherapy: PD-L1 analyse: waar staan we

Personalised Healthcare. will it deliver? Bob Holland Head of Personalised Healthcare & Biomarkers Innovative Medicines AstraZeneca R&D

NGS ONCOPANELS: FDA S PERSPECTIVE

PLENARY SESSION 1: CLINICAL TRIAL DESIGN IN AN ERA OF HORIZONTAL DRUG DEVELOPMENT Industry Perspective

Precision Genetic Testing in Cancer Treatment and Prognosis

NCCN Non-Small Cell Lung Cancer V Meeting June 15, 2018

GENETIC TESTING FOR TARGETED THERAPY FOR NON-SMALL CELL LUNG CANCER (NSCLC)

NGS IN ONCOLOGY: FDA S PERSPECTIVE

Immunotherapy in NSCLC Pathologist role

Strengths and Weaknesses of PD-L1 testing: Pathology perspective

The Current Status of Immune Checkpoint Inhibitors: Arvin Yang, MD PhD Oncology Global Clinical Research Bristol-Myers Squibb

Cancer Immunotherapy Survey

Immune Checkpoint Inhibitors: The New Breakout Stars in Cancer Treatment

Lung Cancer Update on Pathology Zhaolin Xu, MD, FRCPC, FCAP

Approval of pembrolizumab (MSI- H/dMMR) and considerations for site-agnostic development of drugs in oncology

Role of the Pathologist in Guiding Immuno-oncological Therapies. Scott Rodig MD, PhD

PD-L1 and Immunotherapy of GI cancers: What do you need to know

MATCHMAKING IN ONCOLOGY CHALLENGES AND COMBINATION STRATEGY FOR NOVEL TARGETED AGENTS

GLOBAL REGISTRATION STRATEGIES:

QIAGEN's Growing Immuno-Oncology Testing Portfolio

Big data vs. the individual liver from a regulatory perspective

Emerging biomarkers for immunotherapy in lung cancer

Emerging Tissue and Serum Markers

Getting the Whole Picture for Immuno-Oncology Therapies

Targeted Cancer Therapies

HSL-Advanced Diagnostics 2018 / 19 Test & Service List

WHY LOOK FOR ADDITIONAL DATA TO ENRICH THE KAPLAN-MEIER CURVES? Immuno-oncology, only an example

Advances in Pathology and molecular biology of lung cancer. Lukas Bubendorf Pathologie

Assessment Run C1 2017

Companion Diagnostics: Technologies and Markets. Robert Hunter. March Report Code: BIO077C

Review of NEO Testing Platforms. Lawrence M. Weiss, MD Medical Director, Aliso Viejo

Predictive Biomarkers for Pembrolizumab. Eric H. Rubin, M.D.

Emerging Targets in Immunotherapy

NSCLC 2 nd and further line therapies. Egbert F. Smit MD PhD. Dept. Thoracic Oncology, Netherlands Cancer Institute

Delivering on the Promise of Personalised Healthcare

Current experience in immunotherapy for metastatic renal cell carcinoma

Cancer Immunotherapy Patient Forum. for the Treatment of Melanoma, Leukemia, Lymphoma, Lung and Genitourinary Cancers - November 7, 2015

Corporate Medical Policy

PTAC meeting held on 5 & 6 May (minutes for web publishing)

Highlights from AACR 2015: The Emerging Potential of Immunotherapeutic Approaches in Non-Small Cell Lung Cancer

Subgroup Mixable Inference for Targeted Therapies

Immunotherapy and Targeted Therapies: The new face of cancer treatment

Immuno-Oncology Clinical Trials Update: Checkpoint Inhibitors Others (not Anti-PD-L1/PD-1) Issue 4 January 2017

First Phase 3 Results Presented for a PD-1 Immune Checkpoint Inhibitor

Lights and sheds of early approval of new drugs in clinical routine. Carmen Criscitiello, MD, PhD European Institute of Oncology Milan, Italy

ICLIO National Conference

First phase III data on Roche s TECENTRIQ (atezolizumab) to feature at the 2016 European Society for Medical Oncology (ESMO) Congress

A Blueprint for Drug/Diagnostic Development: Facilitating Development and Use of Curated Genetic Databases

Checkpoint Regulators Cancer Immunotherapy takes centre stage. Dr Oliver Klein Department of Medical Oncology 02 May 2015

Lung Cancer Update 2016 BAONS Oncology Care Update

Personalized Therapies for Lung Cancer. Questions & Answers

Immuno-Oncology Applications

Comprehensive genomic profiling for various solid tumors

Diagnostic test Suggested website label Description Hospitals available

New Developments in Cancer Treatment. Ian Rabinowitz MD

Pantoprazole icd 10 code

Corporate Medical Policy

Cancer Immunotherapy Future from the Past?

Cancer Progress. The State of Play in Immuno-Oncology

More cancer patients are being treated with immunotherapy, but

Corporate Medical Policy

Molecular Testing in Lung Cancer

Product Introduction

Immunotherapy in Colorectal cancer

Opportunities and Challenges in the Development of Companion Diagnostics

immunotherapy a guide for the patient

Panel Value Frameworks for Cancer Therapies: Are they Useful in the Context of Canadian Health Technology Assessments and Reimbursement Decisions?

News from ASCO. Niven Mehra, Medical Oncologist. Radboud UMC Institute of Cancer Research and The Royal Marsden Hospital

New Systemic Therapies in Advanced Melanoma

Colorectal Cancer in 2017: From Biology to the Clinics. Rodrigo Dienstmann

IMMUNOTHERAPY FOR LUNG CANCER

Corporate Presentation October 2018 Nasdaq: ADXS

Harnessing Complexity: Companion Diagnostics in Oncology

Corporate Medical Policy

HER2 status assessment in breast cancer. Marc van de Vijver Academic Medical Centre (AMC), Amsterdam

Novartis Oncology. The Precision Oncology Annual Trend Report. Perspectives From Payers, Oncologists, and Pathologists Third Edition

A 10-year summary of kinase small molecule research Text mining AACR abstracts (white paper)

Advancing Health Economics, Services, Policy and Ethics

Array BioPharma Second Quarter of F2018 Update FEBRUARY 6, 2018

LUNG CANCER EARLY MOLECULAR ASSESSMENT KIM MONKHORST WEEK VAN DE PATHOLOGIE 29 MAART

PD-L1 Analyte Control DR

Value-based frameworks in oncology

THE FUTURE OF IMMUNOTHERAPY IN COLORECTAL CANCER. Prof. Dr. Hans Prenen, MD, PhD Oncology Department University Hospital Antwerp, Belgium

Transcription:

Innovation, Uncertainty and Reimbursement Processes in Precision Medicine: The Case of PD-L1 Monday, October 17, 2016 MaRS Discovery District, Toronto This session was generously sponsored by Merck Canada Inc.

Meet the Panel Moderator: Barry Stein (Colorectal Cancer Association of Canada) Speakers: Lillian Siu (Princess Margaret Cancer Centre) Reiner Banken (Reiner Banken Consulting) Scott Gavura (Cancer Care Ontario)

Session Overview Developments in precision medicine provide hope of highly targeted treatments, improving both clinical benefits for patients and effective use of scarce resources in health care. Promising diagnostic tests for selecting groups of patients for treatment are being introduced in health care at an increasingly rapid pace. Early access for high medical need must take into account and manage the uncertainties around value for the patient and for the health system. PD-L1 testing in cancer care is the first example where multiple drugs are targeting the same molecular pathway, each drug with its own companion diagnostic test. In spite of the unprecedented collaboration between the different companies involved (Blueprint Project), the drugs are starting to enter the Canadian Health Care System with great uncertainties on the need and benefits for PD-L1 testing and the appropriate choice of a companion diagnostic test for a specific drug. The session aims for a dialogue on patient, clinician, health technology assessment and payer perspectives on introducing PD-L1 drugs and companion diagnostics under great uncertainty and a rapidly evolving evidence base.

Session Timing 15:00 Reiner Banken Open the session and introduce Barry Stein 15:05 Barry Stein Introduce session and introduces Lillian 15:10 Lillian Siu Presentation 15:20 Barry Stein Introduce Reiner 15:22 Reiner Banken Presentation 15:32 Barry Stein Introduce Scott 15:34 Scott Gavura Presentation 15:44 Barry Stein Presentation 15:50 All Comments from presenters : 2 minutes each 16:00 All Questions from audience 16:13 Barry Stein Closing of session

Promises and Challenges of PD-L1 in Clinical Practice Lillian L. Siu, MD Princess Margaret Cancer Centre, Toronto, Canada CAPT 2016, October 17, 2016, MaRS Discovery District

Interactions Between Antigen Presenting Cells, T Cells and Tumor Cells Antigen presenting cell T cell Tumor cell

Analytical and Clinical Characteristics of Biomarkers Discovery Clinical validity: The test result shows an association with a clinical outcome of interest Analytical validity: The test s performance is established to be accurate, reliable, and reproducible Clinical utility: Use of the test results in a favorable benefit to risk ratio for the patient

Drug Manufacturer Comparison of PD-L1 Assays pembrolizumab (Keytruda, MK-3475) Merck Sharp & Dohme nivolumab (Opdivo, BMS-936558) Bristol-Myers- Squibb durvalumab (MEDI-4736) MedImmune/ AstraZeneca mab humanized IgG4 human IgG4 human Fcmodified IgG1 Target PD-1 PD-1 PD-L1 PD-L1 atezolizumab (MPDL3280A, RG7446) Genentech/ Roche human Fc-modified IgG1 Companion Diagnostic Assay PD-L1+ FDA approved Melanoma, Melanoma, Bladder* Bladder, NSCLC * NSCLC, SCCHN NSCLC, renal, HD IHC assay Dako Dako Ventana Ventana developer Antibody clone 22C3 mouse 28-8 rabbit SP263 rabbit SP142 Expression on TCs and stroma TCs TCs TICs and TCs Cut-off Melanoma, Bladder, NSCLC: 1% TC (or any tumor stroma cell) NSCLC: 1-5% TC Renal: 5% TC NSCLC, SCCHN: 25% TC Bladder, NSCLC, Breast: IHC 2+ 5%-<10% TC or TIC or IHC 3+ 10% TC or TIC * FDA Breakthrough Designation Therapy status TCs = tumor cells; TIC= tumor-infiltrating immune cells; n/a, not applicable Hansen, Siu JAMA Oncology, 2016

Companion vs Complementary Diagnostic Companion Diagnostic: Provides information that is essential for the safe and effective use of a corresponding drug or biological product e.g. PD-L1 IHC 22C3 for pembrolizumab in NSCLC Complementary Diagnostic: Not required but aids risk/benefit assessment fro drug use in individual patients e.g. PD-L1 IHC 28-8 for nivolumab in NSCLC and melanoma, PD-L1 IHC SP142 for atezolizumab in bladder cancer 5

List of FDA Cleared or Approved Companion Diagnostic Devices Drug Name Device Trade Name Drug Name Device Trade Name Trastuzumab Pertuzumab HER2 FISH PharmDx Kit HERCEPTEST Gefitinib Afatinib Therascreen EGFR RGQ PCR Kit Trastuzumab Olaparib Imatinib INSITE HER-2/NEU KIT Bond Oracle Her2 IHC System SPOT-LIGHT HER2 CISH Kit HER2 CISH PharmDx Kit INFORM HER2 DUAL ISH DNA Probe Cocktail PATHVYSION HER2 DNA Probe Kit PATHWAY ANTI-HER2/NEU (4B5) Rabbit Monoclonal Primary Antibody BRACAnalysis CDx DAKO C-KIT PharmDx Erlotinib Crizotinib Cetuximab and Panitumumab Vemurafenib Trametinib Dabrafenib cobas EGFR Mutation Test VENTANA ALK (D5F3) CDx Assay VYSIS ALK Break Apart FISH Probe Kit cobas KRAS Mutation Test COBAS 4800 BRAF V600 Mutation Test THxID BRAF Kit http://www.fda.gov/medicaldevices/productsandmedicalprocedures/invitrodiagnostics/ucm301431.htm

Carbognin L, et al. PLoS One. 2015, 10(6):e0130142.

PD-L1 Assays Challenges: Different antibodies being used Variable definitions for biomarker positivity (which cells/tissue components, different staining thresholds used as cut-offs) Lack of standardization and harmonization Challenging to make comparisons across trials that used different assays with different definitions

Blueprint and Other PD-L1 Comparative Projects The Blueprint Project: Harmonizing Companion Diagnostics Across a Class of Targeted Therapies, AACR 2016; Ratcliffe et al AACR 2016 9

An HTA perspective on Innovation, Uncertainty and Reimbursement: The case of PD-L1 Canadian Association for Population Therapeutics Annual Conference Toronto, October, 17th, 2016 Reiner Banken M.D. M.Sc. Consultant reiner@reinerbanken.com 514 819-8294

Conflicts of interest Work in a governmental HTA agency for many years. Work as a consultant with different companies over the last 12 months. Recent work with Roche Diagnostics on PD-L1 in Canada.

The origin of Health Technology Assessment Request of the US Congress Senate Committee on Human Resources to OTA in 1974: «whether a reasonable amount of justification should be provided before costly new medical technologies and procedures are put into general use» Decisions based on needs expressed by physicians Decisions based on (informed by) a formal and transparent assessment of the evidence

Adapted from Health technology assessment of medical devices. WHO Medical device technical series, 2011. Available at: http://whqlibdoc.who.int/publications/2011/9789241501361_eng.pdf Reasoning in HTA How should we do it here? Should we do it here? Can it work here? (here=context of decisionmaking) Can it work? Implementation Appropriateness Effectiveness and safeness Theoretical safety and efficacy Research HTA depends on available primary studies. HTA must deal with uncertainties in knowledge. HTA can be a hurdle or an enabler for innovations.

The case of PD-L1 PD-L1 assays inform decision-making for PD-L1 immunotherapies for an increasing array of cancers. Rapidly evolving knowledge on the role of PD-L1 immunotherapies in treatment algorithms and the place of PD-L1 assays (ex resistance). Different commercial PD-L1 assays for different PD-L1 drugs and laboratory developed PD-L1 tests (30 to 50% in the US) Patient benefits with PD-L1 immunotherapies, increased for PD-L1 positive cancers Immunotherapies costing around 10 000$ per month, PD-L1 assays around 100$ for each test

Decision-making for introducing PD-L1 tests 1. Mandatory HTA process only in Québec. HTA informing central decisionmaking processes. No decision-making at the hospital level. 2. Fragmented decision-making at the provincial and the hospital level in Ontario, centralised assessment process if dedicated funding. HTA if involvement of HQO. 3. Ad hoc assessment of companion and complementary diagnostics. No integrated assessment frameworks for assays and drugs 4. No evidence development pathways in health systems in Canada (such as real world evidence development, coverage with evidence development, adaptive pathways, living labs) 2016-11-15

Challenges How to provide patient access to PD-L1 assays for patient and for health systems benefit? How to introduce PD-L1 tests under evolving uncertainties of analytic and clinical validity and clinical utility? How to develop dynamic HTA systems linked to collaborative, patient-centered evidence-development pathways?

A Payer s Perspective: Innovation, Uncertainty and Reimbursement Processes in Precision Medicine in Oncology CAPT 2016 Scott Gavura, Director, Provincial Drug Reimbursement Programs

Disclosures The speaker has no financial or other conflicts of interest to report. 2

Balancing funding obligations and demands Financial obligations Treatment expectations

The sustainability challenge NDFP projected growth based on historical increases 12% (10/11-14/15) 4 Drug costs for claims approved under the New Drug Funding Program.

Implementation challenges Drug-specific funding decisions in face of uncertainty Multiple new entrants, simultaneously Further increasing uncertainty Need to ensure testing in place, simultaneously with drug funding Unique drug/test pairing increases challenge. The result: Complexity of incorporating adaptive pathways into population-level funding programs 5

Can we collect and use real-world evidence? The vision: a learning health system/reimbursement system Ideally, link payment to outcomes realized vs. expected/anticipated Validate assumptions we made during our assessment Possible to confirm clinical- and costeffectiveness? Increase overall confidence in our reimbursement decisions Resolve uncertainty remaining from decisionmaking process

Can RWE do all this? Insufficient information often available to demonstrate a new treatment provides a meaningful clinical benefit. Rapid introduction of new therapies means study population may not be representative of target population (e.g., exposure to other therapies) Evolving understanding of PD-L1 expression and relationship with tumor

What data could RWE encompass? Treatment data / Rx claims data Outcomes data Genomic data Socioeconomic data Patient-generated data (e.g., PRO s)

What barriers exist? There s a lack of consensus on the implementation approach. There s an incremental cost to collecting, cleaning maintaining and analyzing datasets developed expressly for RWE use. Build this into implementation plans? We lack a common framework (across multiple stakeholders, gov t and non gov t) that defines how RWE data will be integrated and used.

A Payer s Perspective: Innovation, Uncertainty and Reimbursement Processes in Precision Medicine in Oncology CAPT 2016 scott.gavura@cancercare.on.ca

Immuno-Oncology Policy TO REIMBURSE PD-L1 PREDICTIVE BIOMARKERS OR NOT? THAT IS THE QUESTION. CAPT Toronto October 17, 2016 Barry D. Stein barrys@colorectal-cancer.ca 1

Immuno-oncology Therapies Enabling The Body s Immune System To Fight Cancer Immunotherapy targets the body s immune system, rather than the tumour itself. Selectively recognises & targets cancer cells, not healthy cells. Gives long-lasting memory to the immune system, enabling it to continually adapt to the cancer over time & provide durable, long-term response to cancer with fewer side effects. Several drugs have already been developed and many more are in preclinical and clinical development stage targeting advanced melanoma, lung, bladder, prostate, colorectal and pancreatic cancer, providing hope for patients in some cases where no effective treatments were previously available. How can we ensure patient access to this new and possibly game changing technology? 2

Policymakers, Regulatory Authorities, Health Professionals & Patients Require A Better Understanding of IO In Cancer Treatment The complexity of immuno-therapy drugs, the high number of patients and the high costs of these drugs necessitate a better understanding of IO drugs and their predictive biomarkers being used in clinical practice to identify the appropriate patient for the right drug. IO therapies and their predictive biomarkers are somewhat imprecise and variable, but are being integrated into cancer plans and policies. Need to ensure alignment between regulatory and reimbursement authorities taking into account the benefits of IO. The PD-L1 (Programmed-death ligand1) protein is at the center of clinical decisions for selecting patients who are most likely to benefit from immuno-therapy in connection with checkpoint blockade drugs. 3

PD-L1, New Combinations & Future Biomarkers The next 5-10 years will see an increasing role for immunotherapy and select predictive biomarkers will be vital in determining the appropriate responders. For those that do not respond, we may be able to turn non immunogenic tumours into ones that that become amenable to immunotherapy by doing such things such as combining anti PD-L1 therapies with MEK* inhibitors in Microsatellite-Stable mcrc patients providing more hope for patients. PD-L1 predictive biomarkers are under fire and attention is beginning to turn the possibility of other biomarkers such as TMB (Tumour Mutational Burden). At present however, selecting patients based on PD-L1 expression, however imperfect, seems to be the most significant marker for some types of cancer such as NSCLC as highlighted at the recent ESMO 2016 annual meeting. *A MEK inhibitor is a drug that inhibits mitogen activated protein kinase enzymes MEK1 and or MEK2. They have the potential for treatment in KRAS/BRAF mutated CRC. 4

ANTI PD-L1 THERAPY AT ITS BEST 5