Personalised Medicine

Transcription

1 Personalised Medicine Panacea or Pandora s box? Dr Tom Lillie Oncology Therapeutic Area Head Amgen October 2012

2 Amgen is the world s leading biotechnology company employs more than 17,000 staff in 39 countries develops medicines for patients fighting serious illnesses, including cancer has been a biotechnology pioneer since

3 Panacea? PM is changing medical practice Personalised medicine (PM) is the application of omics revolution to medicine - Precise molecular definition of disease Gene chips, molecular diagnostics, GWAS - Biomarkers for diagnosis, prognosis and therapy ER, HER-2 / 3 / EGF-R, K-RAS, B-RAF, ALK, BCR-ABL - Targeted therapies Antibodies, rational molecular design of small molecules These technologies allows rational treatment of underlying molecular pathology Drugs only given to those likely to benefit - Higher efficacy in target population - Less waste + toxicity as only treat those who will benefit Smaller, faster, cheaper trials in defined populations

4 Pandora s box? PM brings challenges to the drug development model Common diseases are fragmenting - Every disease will be a molecular orphan disease - But many diseases share similar molecular faults, and will have common therapies Small populations of available patients - Trials have to find the right patients - Diagnostics need to be available - Small safety datasets for approval Privacy and use of tumour samples / marker information The target keeps moving - Multiple, interdependent molecular pathways and the escape routes Science moves much faster than clinical trials - Trials slow, expensive, highly regulated, inflexible Often require large trials to find the small population who benefit - Small studies in selected population may miss those who benefit - Neither situation is a sustainable business model Pricing and reimbursement - Value for high efficacy orphan populations - How to accommodate multiple indications with different values?

5 Breast cancer is no longer one disease Bertucci F et al. Cancer Res 2005;65: by American Association for Cancer Research Hierarchical clustering of expression data from Sorlie et al.

6 Cancer signalling pathways

7 Biomarker discovery a success story Amgen published the first Phase 3 data on a potential treatment linked to the KRAS gene, a biomarker for metastatic colorectal cancer (mcrc) 1 - A biomarker can predict whether a patient will respond to a drug Patients with the wild-type KRAS gene are more likely to respond to certain anti-cancer agents, including Amgen s panitumumab 2 In prospective phase 3 studies, panitumumab was the first therapy to demonstrate the potential of KRAS as a predictive biomarker in patients with mcrc 3,4 Discovery of the KRAS gene has helped revolutionise cancer care 1. Amado RG, et al. J Clin Oncol. 2008;26: ; 2. Schmoll HJ, Annals of Oncology 23: , Douillard JY, et al. J Clin Oncol 2010; 28: ; 4. Peeters M, et al. J Clin Oncol 2010; 28:

8 BSC ± panitumumab: Increased PFS in patients with KRAS WT tumours KRAS wild type KRAS mutant Events, n (%) Median PFS (weeks) Events, n (%) Median PFS (weeks) 100% Pmab + BSC 115/124 (93) % Pmab + BSC 76/84 (90) 8.0 Proportion event-free 80% 60% 40% 20% BSC 114/119 (96) 8.0 Pmab + BSC BSC Proportion event-free 80% 60% 40% 20% BSC 95/100 (95) 8.0 Pmab + BSC BSC 0% Weeks HR=0.49 (95% CI, ) Stratified log rank test p< % Weeks HR=1.07 (95% CI, ) Unscheduled tumour assessments were moved to the nearest scheduled timepoint Panitumumab European Public Assessment Report 2011; 8

9 Overall Survival (%) Rilotumumab: exploring the unmet need in gastric cancer Rilotumumab targets hepatocyte growth factor, the only ligand of the MET receptor In gastric cancer, the MET receptor has been indentified as a possible predictive biomarker In a phase II trial, patients with high MET expression who received rilotumumab+ecx chemotherapy lived longer than those who received ECX chemotherapy alone Overall Survival Time (Months) Rilotumumab + ECX (n = 27) Med ian Mo nth s (80 % CI) 11.1 ( ) HR + (95% CI) P Value 0.29 ( ) CI = confidence interval; ECOG PS = Eastern Cooperative Oncology Group Performance Status; ECX = epirubicin, cisplatin, capecitabine; HR = hazard ratio; OS = overall survival; PFS = progression-free survival (4.5 Placebo + ECX (n = 11) *HR adjusted for baseline disease extent and ECOG PS 10.4 Oliner KS, et al. Oral presentation at 2012 ASCO Annual Meeting; June 1-5, 2012; Chicago, IL. Abstract #4005. ) 9

10 How can we move from Pandora s box to panacea? Continue to Invest in innovation - We are in a time of transition which can seem confusing and progress slow - Important new treatment approaches and technologies will emerge from this transition - Europe can be a leader in this area with appropriate legislation and investment Flexible regulatory + reimbursement pathways - Ability to accommodate new science in ongoing studies science moves fast Clear guidance on retrospective analysis of biomarkers on trial samples - fit for purpose diagnostic approval pathway - Old approach of add targeted therapy to existing therapy may not be optimal - Reimbursement approaches that include diagnostic / therapy combo, increased or decreased value, multiple orphan indications Incentivise collaboration - No single company has all the necessary diagnostics / therapies - Bio-banking key for biomarkers - ethics, consent, access and organisation - Public / private collaboration incentives for drug development

11 Conclusions Faster progress in the development of personalised therapies + diagnostics will require new clinical trial, regulatory and reimbursement approaches Personalised medicine has made a substantial impact on cancer treatment - ER, HER-2, K-RAS, ALK, BRCA, B-RAF - But very difficult to prospectively identify - Many adopted into clinical practice without extensive validation Cancer has complex biology - one drug one trial model will not address the multiple growth pathways that sustain cancer survival - Cancers evolve + are heterogeneous treatment resistance a challenge - Genotyping cancer may be a serial exercise Novel approaches have advantages and disadvantages - Will need time and experience for both companies and agencies to understand how to use them effectively - 4 way discussion of academia / industry / regulator / payor will be needed - Collaborative approaches are essential 11