Altria Group, Inc. · NYSE:MO
Altria — Technical Presentation (October 2018)
27 slides from Altria's technical presentation, Oct 26, 2018
Slide 1: The Role of Biomarkers in Assessing Individual Health Risks of Tobacco Products
The Role of Biomarkers in Assessing Individual Health Risks of Tobacco Products Mohamadi Sarkar, M.Pharm., PhD, FCP Fellow, Scientific Strategy and Analysis Altria Client Services, LLC October 26, 2018 Altria Client Services | Mohamadi Sarkar, M.Pharm., PhD, FCP, Fellow | 10-26-18 | CORESTA Biomarke
Slide 2: WHO Perspective on Biomarkers
WHO Perspective on Biomarkers “The WHO Study Group on Tobacco Product Regulation recognizes that effective regulation of tobacco products, particularly products offered as reduced exposure or reduced risk products, can be greatly facilitated by development of validated biomarkers….” “Measuring chang
Slide 3: Biomarkers in Regulatory Submissions
Biomarkers in Regulatory Submissions “FDA recommends that applicants conduct human studies to assess the full range of the human health risks related to the use of the tobacco product, including exposure to tobacco-related compounds (e.g., biomarkers of exposure) and health outcomes (e.g., disease i
Slide 4: FDA's perspective on Biomarkers in MRTPs
FDA’s perspective on Biomarkers in MRTPs “FDA will always promote science based decision making” Statement by FDA Commissioner, Scott Gottleib, M.D. 6/9/2018 “Currently, there is no single biomarker that predicts the risk of disease in people who use tobacco products ” Altria Client Services | Moham
Slide 5: Challenges and Issues with Biomarkers for Smoking Related Diseases
Challenges and Issues with Biomarkers for Smoking Related Diseases Smoking related diseases are complex and multi-factorial Altria Client Services | Mohamadi Sarkar, M.Pharm., PhD, FCP, Fellow | 10-26-18 | CORESTA Biomarker Symposium | DRAFT 5
Slide 6: Smoking related disease: relative risk and risk factors
Smoking related disease: relative risk and risk factors Estimated Number of Estimated % of Cases Disease RR * Risk Factors** Due to Smoking** Men – 23.3 Lung Cancer <5 ~90+ Women – 12.7 Men – 10.6 COPD <5 ~80-90 Women – 13.1 Men – 2.8 CVD >100 ~20+ Women – 3.1 * From CPS-2 as listed in U.S. Departme
Slide 7: Challenges and Issues with Biomarkers for Smoking Related Diseases
Challenges and Issues with Biomarkers for Smoking Related Diseases Smoking related diseases are complex and multi-factorial Significant lag time exists before smokers manifest disease symptoms Altria Client Services | Mohamadi Sarkar, M.Pharm., PhD, FCP, Fellow | 10-26-18 | CORESTA Biomarker Sym
Slide 8: Lag Time Between Exposure and Disease
Lag Time Between Exposure and Disease Trends in Cigarette Consumption and Lung Cancer Death Rates* in the US *Age-adjusted to US population in 2000 Death rates: US Mortality Data, 1960-2009, US Mortality Volumes, 1930-1959, National Center for Health Statistics, Centers for Disease Control and Preve
Slide 9: Challenges and Issues with Biomarkers for Smoking Related Diseases
Challenges and Issues with Biomarkers for Smoking Related Diseases Smoking related diseases are complex and multi-factorial Significant lag time exists before smokers manifest disease symptoms Some of the disease mechanisms are yet to be definitively established e.g. although smoking causes lu
Slide 10: Proposed mechanisms for lung cancer
Proposed mechanisms for lung cancer NNK Chemical Carcinogenesis Chronic Inflammation & Oxidative Stress Altria Client Services | Mohamadi Sarkar, M.Pharm., PhD, FCP, Fellow | 10-26-18 | CORESTA Biomarker Symposium | DRAFT 10
Slide 11: Challenges and Issues with Biomarkers for Smoking Related Diseases
Challenges and Issues with Biomarkers for Smoking Related Diseases Smoking related diseases are complex and multi-factorial Significant lag time exists before smokers manifest disease symptoms Some of the disease mechanisms are yet to be definitively established e.g. although smoking causes lu
Slide 12: Risk Reduction Continuum
Risk Reduction Continuum Smoker Never Smoker Complete Switching Complete Cessation Risk reduction depends on smoking history and time since quitting Altria Client Services | Mohamadi Sarkar, M.Pharm., PhD, FCP, Fellow | 10-26-18 | CORESTA Biomarker Symposium | DRAFT 12
Slide 13: Challenges and Issues with Biomarkers for Smoking Related Diseases
Challenges and Issues with Biomarkers for Smoking Related Diseases Smoking related diseases are complex and multi-factorial Significant lag time exists before smokers manifest disease symptoms Some of the disease mechanisms are yet to be definitively established e.g. although smoking causes lu
Slide 14: Potential Solutions – Utilize multiple lines of evidence in absence of epi data
Potential Solutions – Utilize multiple lines of evidence in absence of epi data Nonclinical Studies (in vitro and in vivo) Biomarkers Biomarkers of Potential of Exposure Harm Modified Risk Product Functional Health Biomarkers Outcomes of Disease Altria Client Services | Mohamadi Sarkar, M.Pharm., Ph
Slide 15: Relationship Between Exposure and Disease
Relationship Between Exposure and Disease Biomarkers of Exposure Genetic Susceptibility & Other Confounders Internal Early Altered Structure EXPOSURE Dose Biologically Effective Dose Biological Effect / Function DISEASE Adapted from: National Research Council. 1987. Biological markers in environment
Slide 16: Association of HPHC to Smoking Related Diseases
Association of HPHC to Smoking Related Diseases Abbreviated HPHC List Disease Association for Cigarette Smoke Stated by FDA Acetaldehyde CA, RT, AD Acrolein RT, CT Acrylonitrile CA, RT 4-Aminobiphenyl CA 1-Aminobiphenyl CA Ammonia RT Benzene CA, RT, RDT Benzo[a]pyrene CA 1,3-Butadiene CA, RT, RDT Ca
Slide 17: Relationship Between Exposure and Disease
Relationship Between Exposure and Disease Biomarkers of Potential Harm Genetic Susceptibility & Other Confounders Internal Early Altered Structure EXPOSURE Dose Biologically Effective Dose Biological Effect / Function DISEASE Adapted from: National Research Council. 1987. Biological markers in envir
Slide 18: Early Indicators of Disease Risk
Early Indicators of Disease Risk Three of the major diseases related to smoking • Lung Cancer • Chronic Obstructive Pulmonary Disease (COPD) • Cardiovascular Disease (CVD) These diseases are complex but some underlying mechanisms are common, e.g. • Chronic Inflammation • Oxidative Stress Referen
Slide 19: Selective List of BOPH
Selective List of BOPH Biomarker Biological Effect Disease Association White Blood Cell Count Inflammation Fibrinogen Inflammation HS C-reactive protein Inflammation/Tissue injury Cardiovascular disease / Inflammation/Endothelial cell Cancer / COPD von Willebrand factor damage Oxidative Stress/Lipid
Slide 20: White Blood Cells and HDL-C
White Blood Cells and HDL-C “A decrease of WBC count of 1,000/µL has been associated with a decrease of 14% in the risk of cardiovascular disease death.” (Brown et al J. Clin. Epidemiol. 2001;54:316-22.) “Epidemiological studies suggest that for every 2-3% increase in HDL-C (independent of LDL-c
Slide 21: Relationship Between Exposure and Disease
Relationship Between Exposure and Disease Functional Biomarkers of Disease Genetic Susceptibility & Other Confounders Internal Early Altered Structure EXPOSURE Dose Biologically Effective Dose Biological Effect / Function DISEASE Adapted from: National Research Council. 1987. Biological markers in e
Slide 22: Selective List of Functional Biomarkers
Selective List of Functional Biomarkers* Representative Biomarker Biological Effect Disease Association %FEV1 / FVC Post-bronchodilator FEV1 or FVC FEF 25-75% Pulmonary Function COPD FeNO Mucociliary Clearance Flow-mediated dilation Endothelial Laser Doppler Flowmetry dysfunction Venous occlusion pl
Slide 23: Health Outcomes
Health Outcomes Health Outcomes Pre-market Assessments - Six-minute walk test - Cough Questionnaire - Quality of Life Measurements Post-market Assessments - Real-world evidence (based on product category) https://www.slideshare.net/IndusHealthPlus/how-quitting-smoking-changes-your-body Reference
Slide 24: Potential solutions
Potential solutions Engage with ICH and/or FDA to harmonize biomarker qualification using the CORESTA platform Altria Client Services | Mohamadi Sarkar, M.Pharm., PhD, FCP, Fellow | 10-26-18 | CORESTA Biomarker Symposium | DRAFT 24
Slide 25: ICH is unique in bringing together regulatory authorities and pharmaceutical industry
ICH* is unique in bringing together the regulatory authorities and pharmaceutical industry to discuss scientific and technical aspects of drug registration. Harmonisation is achieved through the development of ICH Guidelines via a process of scientific consensus with regulatory and industry experts
Slide 26: FDA Biomarker Qualification Program
FDA Biomarker Qualification Program Altria Client Services | Mohamadi Sarkar, M.Pharm., PhD, FCP, Fellow | 10-26-18 | CORESTA Biomarker Symposium | DRAFT 26
Slide 27: Conclusions
Conclusions Scientific evidence from biomarkers can provide relevant information Multiple lines of converging evidence should be considered in regulatory decision making for risk reduction. The closer these reductions are to that achieved from smoking cessation the greater the weight of evidence