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Improving Access to Innovative Cancer Therapies in Canada

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Robin Markowitz and Elizabeth Lye from Lymphoma Canada discussed recent pCODR drug funding requests for innovative cancer therapies and how negative funding recommendations are affecting patient access to effective new treatments.

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Improving Access to Innovative Cancer Therapies in Canada

  1. 1. Improving Access to Innovative Cancer Therapies in Canada Robin Markowitz & Elizabeth Lye
  2. 2. Overview 1. The evolving landscape of cancer treatment 2. Drug approval and reimbursement in Canada 3. Recent trends in pCODR assessment of funding requests submitted with non-RCT data 4. Impact of negative pCODR recommendations on patient access 5. Recommendations to improve access to innovative cancer therapies 6. 2018 – is change underway?
  3. 3. The evolving landscape of cancer treatment • Cancer is a diverse collection of diseases that have different molecular composition, even within histological subtypes. • Many new cancer drugs target discrete molecular aberrations or pathways in tumor cells and consequently are active on smaller subsets of the patients. • Companion diagnostics that measure biomarkers are being increasingly integrated with the drug-development and clinical trials. • Unique tumour characteristics and other health conditions of individual patients are of increasing importance in treatment selection.
  4. 4. From “one drug fits all” to a focused, personalized approach Towards rational, targeted drug design: • Monoclonal antibodies & antibody-drug conjugates • Small molecule protein inhibitors • Cellular immunotherapy • Oncolytic virus therapy
  5. 5. Advances in the molecular characterization of tumors Science Translational Medicine 30 Oct 2013: Vol. 5, Issue 209, pp. 209ra153
  6. 6. Drug access in Canada Regulator (Effect & Safety) CDR (CADTH) HTA (Assess Value) Price Negotiator Decision maker/ funder pCODR (CADTH) QUEBEC (INESSS) HEALTH CANADA Pan Canadian Pharmaceutical Alliance (pCPA) F/P/T Ministries of Health & Cancer Agencies
  7. 7. Drug Access in Canada • Not all drugs approved by Health Canada are publicly funded. • Each province and territory has their own publicly funded prescription drug benefit program. • The drug coverage provided by each of the provinces can vary. • Private insurance may be provided through employers and/or purchased individually.
  8. 8. Accelerated approval of promising new therapies for life-threatening diseases • Priority review can be granted for promising new drug products. • In such cases, an NOC with conditions (NOC/c) may be issued. • An NOC/c is authorization to market a drug with the condition that the manufacturer undertakes additional studies to verify the clinical benefit or other conditions required by Health Canada. • Manufacturers seeking an NOC/c often submit data from non- comparative phase I and II clinical trials, while awaiting the results of RCTs or other clinical studies.
  9. 9. Growing gap in access to innovative cancer drug therapies Health Canada has granted an NOC/c for several innovative cancer therapies with limited clinical data, but where the clinical benefit is promising: • there is no alternative therapy available on the Canadian market; or • the new drug represents a significant improvement in the benefit/risk profile over existing treatments. Between 2012-2017, pCODR increasingly recommended that these therapies NOT be reimbursed.
  10. 10. pCODR recommendations: 2012-2017 • Between January 1, 2012 and December 31, 2017, pCODR issued recommendations for 99 oncology drug funding requests. • Submissions supported by limited data sets (i.e. non-comparative data) accounted for 20% (20/99). 0 5 10 15 20 25 2012 2013 2014 2015 2016 2017 RCT non-RCT 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 2012 2013 2014 2015 2016 2017 RCT non-RCT
  11. 11. pCODR Recommendations: 2012-2017 Only non-comparative trial data (N=20) RCT data (N=79) 8.5 (42%)11.5 (58%) Positive Negative 66.5 (84%) 12.5 (16%) Positive Negative
  12. 12. pCODR Recommendations: 2012-2017 Only non-comparative trial data (N=20) RCT data (N=79) 0 2 1 4 0.5 11 0 0 2 6.5 2 0 1 2 3 4 5 6 7 8 2012 2013 2014 2015 2016 2017 NumberofDecisions Date of Recommendation Positive Negative 7 13.5 7 14 13 12 2 2.5 2 3 1 2 0 2 4 6 8 10 12 14 16 18 2012 2013 2014 2015 2016 2017 NumberofDecisions Date of Recommendation Positive Negative
  13. 13. Common conclusions in pERC recommendations • Positive recommendation • Significant unmet need • Lack of existing safe and/or effective treatment options • Small patient population • Infeasibility to conduct RCT in target population • Negative recommendation • Uncertainty of net clinical benefit due to non-comparative data (despite acknowledgement of clinical efficacy, e.g. anti-tumour activity) • Ongoing RCT or feasibility to conduct RCT in target population • High potential budget impact (approx. 50%)
  14. 14. pCODR recommendations: 2012-2017 Drug Product Funding Request Recommen- dation Date Recommendation Reasons for decision Crizotinib NSCLC, ALK- positive, advanced 2012-10-04 *Negative  Not confident of net clinical benefit due to limitations of evidence  Ongoing RCTs Brentuximab vedotin Hodgkin lymphoma, 3rd line 2013-08-29 Positive  Small population  No other treatment options  Infeasible to conduct a RCT Brentuximab vedotin Systemic ALCL, 2nd line 2013-12-05 Positive  Aggressive form of the disease  No other effective, non-toxic treatment options  Infeasible to conduct a RCT Vismodegib Basal cell carcinoma, advanced 2014-01-10 Positive  No standard treatment  Small population  Infeasible to conduct a RCT Bosutinib CML, 2nd-line or more 2015-04-21 Positive  Less toxic than existing treatments  Decreased risk of exacerbating comorbidities  Infeasible to conduct a RCT Romidepsin PTCL, 2nd-line, transplant ineligible 2015-05-19 Positive  Aggressive form of the disease  No other effective treatment options  Small population  RCT feasible, but uncertain it would inform clinical value Aldesleukin Melanoma, metatstatic 2015-06-22 Positive  No standard treatment  Toxicities of existing therapies  Small population Pertuzumab Breast Cancer, 1st- line 2015-07-16 Negative  Uncertainty around net clinical benefit due to validity of surrogate endpoint  Ongoing RCT Ponatinib CML / ALL 2015-10-01 Positive  No treatment options for the disease sub-group  Manageable toxicities  Infeasible to conduct RCT Ceritinib NSCLC, ALK- positive, relapsed/refractory 2015-12-03 *Negative  Not confident of net clinical benefit due to limitations of evidence  Ongoing RCT Blinatumomab ALL, Adult, relapsed/refractory 2016-04-01 *Negative (2nd line) Positive (3rd line)  Not confident of net clinical benefit due to limitations of evidence  Ongoing RCT  Small population  Limited treatment options in this setting Palbociclib Breast Cancer, ER+/her2-, 1st-line 2016-05-05 *Negative  Not confident of net clinical benefit due to limitations of evidence  Ongoing RCT Olaparib Ovarian Cancer, 2nd- line maintenance 2016-09-29 *Negative  Not confident of net clinical benefit due to limitations of evidence  Ongoing RCT Idelalisib Follicular Lymphoma, 3rd-line 2016-09-29 Negative  Not confident of net clinical benefit due to limitations of evidence  Feasible to conduct RCT Ibrutinib WM lymphoma, 2nd- line 2016-11-03 Negative  Not confident of net clinical benefit due to limitations of evidence  Feasible to conduct RCT Daratumumab Multiple myeloma, 4th-line 2016-12-01 Negative  Not confident of net clinical benefit due to limitations of evidence  Feasible to conduct RCT Venetoclax CLL, del(17p), 2nd- line 2016-12-01 Negative  Not confident of net clinical benefit due to limitations of evidence  Feasible to conduct RCT Alectinib NSCLC, ALK+, CNS, relapsed 2017-03-03 Negative  Not confident of net clinical benefit due to limitations of evidence  Ongoing RCT Blinatumomab ALL, pediatric, Ph-, relapsed 2017-08-23 Positive  May be net clinical benefit  Substantial need for treatment options in small population Dabrafenib + trametinib NSCLC, relapsed with BRAF V600 mutation 2017-11-17 Negative  Not confident of net clinical benefit due to limitations of evidence  Feasible to conduct RCT *The funding request received a positive funding recommendation after resubmission with results from a phase III RCT. Abbreviations: ALL: acute lymphoblastic leukemia; ALK: anaplastic lymphoma kinase; CLL: chronic lymphocytic leukemia; CML: chronic myelogenous leukemia; NSCLC: non-small cell lung cancer; PTCL: peripheral T cell lymphoma; RCT: randomized controlled trial; WM: Waldenstrom’s macroglobulinemia
  15. 15. Feasibility & Applicability of RCTs • RCTs considered “gold standard” of empirical medical knowledge – a source of reliable evidence regarding which treatments will most benefit patients • RCTs not always appropriate, feasible or ethical for evaluation of new therapeutic interventions: – Rare diseases – Distinct molecular subtypes – Evidence of significant improvement in clinical endpoints in early trials – Heavily pre-treated populations - lack of common comparator – In rapidly-evolving therapeutic areas, results often outdated before publication – Lack of interest on part of manufacturers
  16. 16. Example 1 Ibrutinib for relapsed Waldenstrom’s Macroglobulinemia: Negative pCODR Recommendation (November, 2016) • pERC: – Noted ibrutinib’s ability to control symptoms, with fewer toxic side effects than available therapies, in an easy to take-at-home pill format that is extremely important to patients. – Not confident of net clinical benefit due to limitations of evidence. – Believed phase III RCT is feasible in this population. • CGP: – WM has annual incidence of 5/million in Canada, making it difficult to recruit enough patients to evaluate important clinical endpoints in an RCT. – Treatment choice is largely guided by data from non-comparative phase II studies and prior treatment history, therefore making comparisons between currently available agents and new therapies challenging. – No standard treatment for relapsed WM, limiting the feasibility of assessing ibrutinib against a single comparator in this setting.
  17. 17. Example 2 Daratumumab (+ dexamethasone) for 4th-line Multiple Myeloma (December, 2016) • pERC: – Not confident of net clinical benefit due to limitations of evidence. – Believed RCT would be feasible to determine efficacy compared with available treatment options or best supportive care. • CGP: – RCT comparing daratumumab to best supportive care not feasible for pragmatic and ethical reasons: – Patients would likely decline participation in a study that may not provide them with an active treatment and opt for one that ensures delivery of another potentially efficacious agent. – Unethical to enroll patients in a trial comparing daratumumab with best supportive care when the toxicity and effectiveness of the suggested best supportive care had proven detrimental to these patients
  18. 18. Impact of negative pCODR recommendations on access Funding requests that receive a negative recommendation from pCODR are very unlikely to receive funding from public drug plans. – All submissions which received negative recommendations and requested pCPA negotiations resulted in pCPA deciding “not to negotiate collectively or individually at the provincial-territorial level” Private payers are increasingly relying on public HTA recommendations to inform their reimbursement criteria for innovative, high-priced therapies. As of December 31, 2017, only 5 funding requests that initially received negative recommendations (based on non-comparative data), were resubmitted with evidence from RCTs. – All subsequently received positive recommendation; however resubmission resulted in access delays up to 515 days.
  19. 19. Recommendations 1. Funding recommendations conditional on collection of additional evidence. Canadian Agency for Drugs and Technologies in Health, Recommendation Framework for CADTH Common Drug Review and pan-Canadian Oncology Drug Review Programs, 2016
  20. 20. Recommendations 1. Funding recommendations conditional on collection of additional evidence 2. Collection and sharing of real-world evidence
  21. 21. 2018 pCODR Recommendations Drug product Funding Request Initial Recommendation Final Recommendation Venetoclax CLL, 3rd-line or more Negative Positive/c: improvement in CE in the form of a substantial price reduction until more robust clinical data are made available for future assessment Pembrolizumab Hodgkin Lymphoma, 3rd- line or more Positive for 2 subsets/ Negative for 1 Positive for 2 subsets/ Negative for 1 Nivolumab Hodgkin Lymphoma, 3rd- line or more Positive for 1 subsets/ Negative for 1 Not yet available Avelumab Merkel cell carcinoma, relapsed Positive Positive Olaratumab Soft-tissue sarcoma Positive/c: time-limited reimbursement until more robust clinical data can be collected for future assessment Not yet available
  22. 22. Canadian Cancer Survivor Network Contact Info Canadian Cancer Survivor Network 1750 Courtwood Crescent, Suite 210 Ottawa, ON K2C 2B5 Telephone / Téléphone : 613-898-1871 E-mail jmanthorne@survivornet.ca or mforrest@survivornet.ca Web site www.survivornet.ca Instagram: @survivornet_ca Twitter: @survivornetca Facebook: www.facebook.com/CanadianSurvivorNet Pinterest: http://pinterest.com/survivornetwork/

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